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Salama, Joseph Kamel

Overview:

Development of novel radiation treatment techniques for patients with limited metastatic disease, and integration of these treatments with systemic therapies. Treatment of head and neck cancers with chemotherapy, radiation and novel targeted drugs. Improving outcomes for medically inoperable patients with lung cancer with new radiation methods. Developing predictors for toxicity of patients treated with chemotherapy and radiation therapy for non-small cell and small cell lung cancer.

Positions:

Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2001

M.D. — Baylor College of Medicine

Transitional Year Resident, Radiation Oncology

University of Texas Medical School at Houston

Resident, Radiation Oncology

University of Chicago

Chief Resident, Radiation Oncology

University of Chicago

Publications:

Radiotherapy and Small Cell Carcinoma With Paraneoplastic Polyneuropathy: A Case Report.

Authors
Natarajan, BD; Jacobs, CD; Salama, JK
MLA Citation
Natarajan, Brahma D., et al. “Radiotherapy and Small Cell Carcinoma With Paraneoplastic Polyneuropathy: A Case Report..” Ann Intern Med, June 2019. Pubmed, doi:10.7326/L19-0236.
PMID
31234207
Source
pubmed
Published In
Ann Intern Med
Publish Date
2019
DOI
10.7326/L19-0236

Retrospective analysis of safety and efficacy of anti-PD-1 therapy and radiation therapy in advanced melanoma: A bi-institutional study.

BACKGROUND AND PURPOSE: Antibodies against programmed cell death protein 1 (PD-1) are standard treatments for advanced melanoma. Palliative radiation therapy (RT) is commonly administered for this disease. Safety and optimal timing for this combination for melanoma has not been established. MATERIALS AND METHODS: In this retrospective cohort study, records for melanoma patients who received anti-PD-1 therapy at Duke University or Emory University (1/1/2013-12/30/2015) were reviewed. Patients were categorized by receipt of RT and RT timing relative to anti-PD-1. RESULTS: 151 patients received anti-PD-1 therapy. Median follow-up was 12.9 months. Patients receiving RT (n = 85) had worse baseline prognostic factors than patients without RT (n = 66). One-year overall survival (OS) was lower for RT patients than patients without RT (66%, 95% CI: 55-77% vs 83%, 95% CI: 73-92%). One-year OS was 61% for patients receiving RT before anti-PD-1 (95% CI: 46-76%), 78% for RT during anti-PD-1 (95% CI: 60-95%), and 58% for RT after anti-PD-1 (95% CI: 26-89%). On Cox regression, OS for patients without RT did not differ significantly from patients receiving RT during anti-PD-1 (HR 1.07, 95% CI: 0.41-2.84) or RT before anti-PD-1 (HR 0.56, 95% CI: 0.21-1.45). RT and anti-PD-1 therapy administered within 6 weeks of each other was well tolerated. CONCLUSION: RT can be safely administered with anti-PD-1 therapy. Despite worse baseline prognostic characteristics for patients receiving RT, OS was similar for patients receiving concurrent RT with anti-PD-1 therapy compared to patients receiving anti-PD-1 therapy alone.

Authors
Mowery, YM; Patel, K; Chowdhary, M; Rushing, CN; Roy Choudhury, K; Lowe, JR; Olson, AC; Wisdom, AJ; Salama, JK; Hanks, BA; Khan, MK; Salama, AKS
MLA Citation
Mowery, Yvonne M., et al. “Retrospective analysis of safety and efficacy of anti-PD-1 therapy and radiation therapy in advanced melanoma: A bi-institutional study..” Radiother Oncol, vol. 138, June 2019, pp. 114–20. Pubmed, doi:10.1016/j.radonc.2019.06.013.
PMID
31252292
Source
pubmed
Published In
Radiother Oncol
Volume
138
Publish Date
2019
Start Page
114
End Page
120
DOI
10.1016/j.radonc.2019.06.013

Salvage Radiotherapy for Recurrent Prostate Cancer: Can the Prognostic Grade Group System Inform Treatment Timing?

PURPOSE: In order to better time salvage radiotherapy (SRT) for post-radical prostatectomy biochemical failure, we examined the association between pre-SRT prostate-specific antigen (PSA) and PSA control as a function of the new prognostic grade group (PGG) system. PATIENTS AND METHODS: Using the Shared Equal Access Regional Cancer Hospital database, we identified men after radical prostatectomy with PSA > 0.2 ng/mL and without cancer involvement of lymph nodes who underwent SRT alone. SRT failure was defined as post-SRT PSA nadir + 0.2 ng/mL or receipt of post-SRT hormone therapy. Men were stratified by pre-SRT PSA (0.2-0.49, 0.5-0.99, and ≥ 1.0 ng/mL). Multivariable Cox models were used to test the association between pre-SRT PSA and SRT failure, stratified by PGG. RESULTS: A total of 358 men met the inclusion criteria and comprised our study cohort. Median post-SRT follow-up was 78 months. A total of 174 men (49%) had pre-SRT PSA 0.2-0.49 ng/mL, 97 (27%) PSA 0.5-0.99 ng/mL, and 87 (24%) PSA ≥ 1.0 ng/mL. On multivariable analysis among men with PGG 1-2, pre-SRT PSA 0.2-0.49 ng/mL had similar outcomes as PSA 0.5-0.99 ng/mL; those with PSA ≥ 1.0 ng/mL had higher recurrence risks (hazard ratio = 2.78, P < .001). Among PGG 3-5, PSA 0.5-0.99 ng/mL or ≥ 1.0 ng/mL had a higher recurrence risk (hazard ratio = 2.15, P = .021; and hazard ratio = 2.49, P = .010, respectively) versus PSA 0.2-0.49 ng/mL. CONCLUSION: In men with higher-grade prostate cancer (PGG 3-5), SRT should be provided earlier (PSA < 0.5 ng/mL), while among men with lower-grade disease (PGG 1-2), SRT results in equal PSA control up to PSA 1.0 ng/mL.

Authors
Tay, KJ; Polascik, TJ; Howard, LE; Salama, JK; Schulman, AA; Chen, Z; Amling, CL; Aronson, WJ; Cooperberg, MR; Kane, CJ; Terris, MK; Freedland, SJ
MLA Citation
Tay, Kae Jack, et al. “Salvage Radiotherapy for Recurrent Prostate Cancer: Can the Prognostic Grade Group System Inform Treatment Timing?.” Clin Genitourin Cancer, May 2019. Pubmed, doi:10.1016/j.clgc.2019.05.007.
PMID
31257075
Source
pubmed
Published In
Clin Genitourin Cancer
Publish Date
2019
DOI
10.1016/j.clgc.2019.05.007

A Nomogram for Testosterone Recovery After Combined Androgen Deprivation and Radiation Therapy for Prostate Cancer.

PURPOSE: Testosterone recovery (TR) after androgen deprivation therapy (ADT) and radiation therapy (RT) is not well characterized. We studied TR in men who received RT and either short-term ADT (STADT) or long-term ADT (LTADT) and aimed to create a nomogram to predict TR. METHODS AND MATERIALS: We identified consecutive localized prostate cancer patients treated with ADT-RT at 2 academic medical centers from January 2011 to October 2016 with documented baseline testosterone. TR was time from last ADT injection to testosterone normalization. The Kaplan-Meier method was used to estimate time to TR. Cox proportional hazards models identified TR predictors. A nomogram was trained with site 1 and externally validated with site 2. RESULTS: A total of 340 patients were included; 69.7% received STADT for a median duration of 6 months; 30.3% received LTADT for a median duration of 24.3 months. Median follow-up was 26.7 months. Median time for TR was 17.2 months for STADT and 24.0 months for LTADT patients (P = .004). The 2-year cumulative incidence of TR was 53.1% after LTADT versus 65.7% after STADT (P = .004). On multivariate analysis, shorter duration ADT (hazard ratio [HR], 0.96; P = .004), higher pretreatment testosterone (HR, 1.004; P < .001), and lower body mass index (HR, 0.95; P = .002) were associated with shorter time to TR. Older age (HR, 0.97; P = .09) and white race (HR, 0.67; P = .06) trended as longer TR predictors. A nomogram was generated to predict probability of TR at 1, 2, and 3 years. The concordance index was 0.71 (95% confidence interval, 0.64-0.78) for the validation cohort. CONCLUSIONS: In this population of localized prostate cancer patients, TR after ADT-RT was variable. Using baseline testosterone, ADT duration, body mass index, age, and race, a predictive nomogram can estimate the likelihood of TR.

Authors
Spiegel, DY; Hong, JC; Oyekunle, T; Waters, L; Lee, WR; Salama, JK; Koontz, BF
MLA Citation
Spiegel, Daphna Y., et al. “A Nomogram for Testosterone Recovery After Combined Androgen Deprivation and Radiation Therapy for Prostate Cancer..” Int J Radiat Oncol Biol Phys, vol. 103, no. 4, Mar. 2019, pp. 834–42. Pubmed, doi:10.1016/j.ijrobp.2018.11.007.
PMID
30419308
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
103
Issue
4
Publish Date
2019
Start Page
834
End Page
842
DOI
10.1016/j.ijrobp.2018.11.007

Long-term Clinical Outcomes of Nonoperative Management With Chemoradiotherapy for Locally Advanced Rectal Cancer in the Veterans Health Administration.

PURPOSE: Standard therapy for locally advanced rectal cancer includes neoadjuvant chemoradiation and surgery. Complete response (CR) rates after chemoradiation can be as high as 29%, suggesting that nonoperative management (NOM) may be reasonable with appropriately selected patients. We sought to identify potential NOM candidates. METHODS AND MATERIALS: Using the Veterans Administration Central Cancer Registry, patients with stage II to III rectal cancer receiving chemoradiation with or without subsequent surgery were identified. Clinical CR (cCR) was assessed by physical examination, endoscopy, or imaging. Kaplan-Meier and log-rank tests were used to assess survival; multivariate analysis was performed using Cox proportional hazards. RESULTS: A total of 1313 patients were identified. Of these, 313 received chemoradiation alone (CRT cohort); 1000 received chemoradiation followed by surgery (CRT + S cohort). Median follow-up was 67.2 months. Median overall survival (OS) was 68.5 months. Median OS was 30.6 months for CRT and 89.3 months for CRT + S (P < .001). Median disease-specific survival (DSS) was 44.8 months for CRT and not reached (NR) for CRT + S (P < .001). Sixty-five CRT patients (20.8%) had a cCR. Median OS for CRT cCR patients was 73.5 months (P = .128 vs CRT + S); median DSS was NR (P = .161 vs CRT + S). One hundred thirty-seven (10.5%) CRT + S patients had a pathologic CR (pCR). Median OS with pCR was 133.7 months (P < .001 vs CRT cCR), and median DSS was NR (P = .276 vs CRT cCR). CONCLUSIONS: CRT patients with cCR had similar OS and DSS versus CRT + S patients and similar DSS versus CRT + S patients with a pCR. This suggests that patients with locally advanced rectal cancer with a cCR to CRT have an excellent prognosis and may be candidates for organ preservation.

Authors
Spiegel, DY; Boyer, MJ; Hong, JC; Williams, CD; Kelley, MJ; Moore, H; Salama, JK; Palta, M
MLA Citation
Spiegel, Daphna Y., et al. “Long-term Clinical Outcomes of Nonoperative Management With Chemoradiotherapy for Locally Advanced Rectal Cancer in the Veterans Health Administration..” Int J Radiat Oncol Biol Phys, vol. 103, no. 3, Mar. 2019, pp. 565–73. Pubmed, doi:10.1016/j.ijrobp.2018.10.018.
PMID
30359718
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
103
Issue
3
Publish Date
2019
Start Page
565
End Page
573
DOI
10.1016/j.ijrobp.2018.10.018

Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry.

Background: Accurate staging for small cell lung cancer (SCLC) is critical for determining appropriate therapy. The clinical impact of increasing PET adoption and stage migration is well described in non-small cell lung cancer but not in SCLC. The objective of this study was to evaluate temporal trends in PET staging and survival in the Veterans Affairs Central Cancer Registry and the impact of PET on outcomes. Patients and Methods: Patients diagnosed with SCLC from 2001 to 2010 were identified. PET staging, overall survival (OS), and lung cancer-specific survival (LCSS) were assessed over time. The impact of PET staging on OS and LCSS was assessed for limited-stage (LS) and extensive-stage (ES) SCLC. Results: From 2001 to 2010, PET use in a total of 10,135 patients with SCLC increased from 1.1% to 39.2%. Median OS improved for all patients (from 6.2 to 7.9 months), those with LS-SCLC (from 10.9 to 13.2 months), and those with ES-SCLC (from 5.0 to 7.0 months). Among staged patients, the proportion of ES-SCLC increased from 63.9% to 65.7%. Among 1,536 patients with LS-SCLC treated with concurrent chemoradiotherapy, 397 were staged by PET. In these patients, PET was associated with longer OS (median, 19.8 vs 14.3 months; hazard ratio [HR], 0.78; 95% CI, 0.68-0.90; P<.0001) and LCSS (median, 22.9 vs 16.7 months; HR, 0.74; 95% CI, 0.63-0.87; P<.0001) with multivariate adjustment and propensity-matching. In the 6,143 patients with ES-SCLC, PET was also associated with improved OS and LCSS. Conclusions: From 2001 to 2010, PET staging increased in this large cohort, with a corresponding relative increase in ES-SCLC. PET was associated with greater OS and LCSS for LS-SCLC and ES-SCLC, likely reflecting stage migration and stage-appropriate therapy. These findings emphasize the importance of PET in SCLC and support its routine use.

Authors
Hong, JC; Boyer, MJ; Spiegel, DY; Williams, CD; Tong, BC; Shofer, SL; Moravan, MJ; Kelley, MJ; Salama, JK
MLA Citation
Hong, Julian C., et al. “Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry..” J Natl Compr Canc Netw, vol. 17, no. 2, Feb. 2019, pp. 127–39. Pubmed, doi:10.6004/jnccn.2018.7090.
PMID
30787126
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
17
Issue
2
Publish Date
2019
Start Page
127
End Page
139
DOI
10.6004/jnccn.2018.7090

Knowledge-Based Statistical Inference Method for Plan Quality Quantification.

AIM: The aim of the study is to develop a geometrically adaptive and statistically robust plan quality inference method. METHODS AND MATERIALS: We propose a knowledge-based plan quality inference method that references to similar plans in the historical database for patient-specific plan quality evaluation. First, a novel plan similarity metric with high-dimension geometrical difference quantification is utilized to retrieve similar plans. Subsequently, dosimetric statistical inferences are obtained from the selected similar plans. Two plan quality metrics-dosimetric result probability and dose deviation index-are proposed to quantify plan quality among prior similar plans. To evaluate the performance of the proposed method, we exported 927 clinically approved head and neck treatment plans. Eight organs at risk, including brain stem, cord, larynx, mandible, pharynx, oral cavity, left parotid and right parotid, were analyzed. Twelve suboptimal plans identified by dosimetric result probability were replanned to validate the capability of the proposed methods in identifying inferior plans. RESULTS: After replanning, left and right parotid median doses are reduced by 31.7% and 18.2%, respectively; 83% of these cases would not be identified as suboptimal without the proposed similarity plan selection. Analysis of population plan quality reveals that average parotid sparing has been improving significantly over time (21.7% dosimetric result probability reduction from year 2006-2007 to year 2016-2017). Notably, the increasing dose sparing over time in retrospective plan quality analysis is strongly correlated with the increasing dose prescription ratios to the 2 planning targets, revealing the collective trend in planning conventions. CONCLUSIONS: The proposed similar plan retrieval and analysis methodology has been proven to be predictive of the current plan quality. Therefore, the proposed workflow can potentially be applied in the clinics as a real-time plan quality assurance tool. The proposed metrics can also serve the purpose of plan quality analytics in finding connections and historical trends in the clinical treatment planning workflow.

Authors
Zhang, J; Wu, QJ; Ge, Y; Wang, C; Sheng, Y; Palta, J; Salama, JK; Yin, F-F; Zhang, J
MLA Citation
Zhang, Jiang, et al. “Knowledge-Based Statistical Inference Method for Plan Quality Quantification..” Technol Cancer Res Treat, vol. 18, Jan. 2019. Pubmed, doi:10.1177/1533033819857758.
PMID
31221025
Source
pubmed
Published In
Technology in Cancer Research & Treatment
Volume
18
Publish Date
2019
Start Page
1533033819857758
DOI
10.1177/1533033819857758

Nonuniform Planning Target Volume Margins for Prostate Bed on the Basis of Surgical Clips on Daily Cone Beam Computed Tomography.

Purpose: We hypothesized that the interfraction motions of the superior and inferior prostate beds differ and therefore require different margins. In this study, we used daily cone beam computed tomography (CBCT) to evaluate the motion of postprostatectomy surgical clips (separated to superior and inferior portions) within the planning target volume (PTV) to derive data-driven PTV margins. Methods and Materials: Our study cohort included consecutive patients with identifiable surgical clips undergoing prostate bed irradiation with daily CBCT image guidance. We identified and contoured the clips within the PTV on the planning computed tomography and CBCT scans. All CBCT scans were registered to the planning computed tomography scan on the basis of pelvic bony structures. The superior border of the pubic symphysis was used to mark the division between the superior and inferior portions. Results: Eleven patients with 263 CBCT scans were included in the cohort. In the left-right direction, the global mean M, systematic error Σ, and residue error σ were 0.02, 0.03, and 0.16 cm, respectively, for superior clips, and 0.00, 0.03, and 0.03 cm, respectively, for inferior clips. In the anterior-posterior direction, the corresponding values were M = 0.01, Σ = 0.25, and σ= 0.37, respectively, for superior, and M = 0.08, Σ= 0.13, σ= 0.15, respectively, for inferior. In the superior-inferior direction, the values were M =-0.06, Σ= 0.23, and σ= 0.27, respectively, for superior, and M =-0.01, Σ= 0.21, σ= 0.20, respectively, for inferior. The results of the 2-tailed F tests showed that the anterior-posterior motion is statistically different between the superior and inferior portions in the anterior-posterior direction. There is no statistical difference in the superior-inferior and lateral directions. Therefore, we propose a set of nonuniform PTV margins (based on the formula 2.5 Σ+ 0.7σ) as 0.2 cm for all prostate beds in the left-right direction, 0.7 cm for all in superior-inferior, and 0.9 to 0.4 for superior-inferior in the anterior-posterior direction. Conclusions: The difference in motion between the superior and inferior portions of the prostate bed is statistically insignificant in the left-right and superior-inferior directions, but statistically significant in the anterior-posterior direction, which warrants a nonuniform PTV margin scheme.

Authors
Song, H; Salama, JK; Lee, WR; Wu, Q
MLA Citation
Song, Haijun, et al. “Nonuniform Planning Target Volume Margins for Prostate Bed on the Basis of Surgical Clips on Daily Cone Beam Computed Tomography..” Adv Radiat Oncol, vol. 4, no. 1, Jan. 2019, pp. 186–90. Pubmed, doi:10.1016/j.adro.2018.09.014.
PMID
30706027
Source
pubmed
Published In
Advances in Radiation Oncology
Volume
4
Issue
1
Publish Date
2019
Start Page
186
End Page
190
DOI
10.1016/j.adro.2018.09.014

Hypofractionated Image-Guided Radiation Therapy With Simultaneous-Integrated Boost Technique for Limited Metastases: A Multi-Institutional Analysis.

Purpose: To perform a multi-institutional analysis following treatment of limited osseous and/or nodal metastases in patients using a novel hypofractionated image-guided radiotherapy with simultaneous-integrated boost (HIGRT-SIB) technique. Methods: Consecutive patients treated with HIGRT-SIB for ≤5 active metastases at Duke University Medical Center or Durham Veterans' Affairs Medical Center between 2013 and 2018 were analyzed to determine toxicities and recurrence patterns following treatment. Most patients received 50 Gy to the PTVboost and 30 Gy to the PTVelect simultaneously in 10 fractions. High-dose treatment volume recurrence (HDTVR) and low-dose treatment volume recurrence (LDTVR) were defined as recurrences within PTVboost and PTVelect, respectively. Marginal recurrence (MR) was defined as recurrence outside PTVelect, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as recurrences not meeting HDTVR, LDTVR, or MR criteria. Freedom from pain recurrence (FFPR) was calculated in patients with painful osseous metastases prior to HIGRT-SIB. Outcome rates were estimated at 12 months using the Kaplan-Meier method. Results: Forty-two patients met inclusion criteria with 59 sites treated with HIGRT-SIB (53% nodal and 47% osseous). Median time from diagnosis to first metastasis was 31 months and the median age at HIGRT-SIB was 69 years. The most common primary tumors were prostate (36%), gastrointestinal (24%), and lung (24%). Median follow-up was 11 months. One acute grade ≥3 toxicity (febrile neutropenia) occurred after docetaxel administration immediately following HIGRT-SIB. Four patients developed late grade ≥3 toxicities: two ipsilateral vocal cord paralyzes and two vertebral compression fractures. The overall pain response rate was 94% and the estimated FFPR at 12 months was 72%. The estimated 12 month rate of HDTVR, LDTVR, MR, and DR was 3.6, 6.2, 7.6, and 55.8%, respectively. DR preceded MR, HDTVR, or LDTVR in each instance. The estimated 12 month probability of in-field and marginal control was 90.0%. Conclusion: Targeting areas at high-risk for occult disease with a lower radiation dose, while simultaneously boosting gross disease with HIGRT in patients with limited osseous and/or nodal metastases, has a high rate of treated metastasis control, a low rate of MR, acceptable toxicity, and high rate of pain palliation. Further investigation with prospective trials is warranted.

Authors
Jacobs, CD; Palta, M; Williamson, H; Price, JG; Czito, BG; Salama, JK; Moravan, MJ
MLA Citation
Jacobs, Corbin D., et al. “Hypofractionated Image-Guided Radiation Therapy With Simultaneous-Integrated Boost Technique for Limited Metastases: A Multi-Institutional Analysis..” Front Oncol, vol. 9, 2019. Pubmed, doi:10.3389/fonc.2019.00469.
Website
https://hdl.handle.net/10161/19054
PMID
31214509
Source
pubmed
Published In
Frontiers in Oncology
Volume
9
Publish Date
2019
Start Page
469
DOI
10.3389/fonc.2019.00469

Evaluation of Post-Stereotactic Body Radiation Therapy Response Assessment for Hepatocellular Carcinoma: An Appraisal of RECIST, m-RECIST and WHO Criteria

Authors
Godfrey, DJ; Vernuccio, F; Stephens, SJ; Salama, JK; Marin, D; Palta, M
MLA Citation
Godfrey, D. J., et al. “Evaluation of Post-Stereotactic Body Radiation Therapy Response Assessment for Hepatocellular Carcinoma: An Appraisal of RECIST, m-RECIST and WHO Criteria.” International Journal of Radiation Oncology*Biology*Physics, vol. 102, no. 3, Elsevier BV, 2018, pp. e53–e53. Crossref, doi:10.1016/j.ijrobp.2018.07.473.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
102
Issue
3
Publish Date
2018
Start Page
e53
End Page
e53
DOI
10.1016/j.ijrobp.2018.07.473

Phase I Trial of Stereotactic Body Radiation Therapy (SBRT) to Multiple Metastatic Sites: A NRG Oncology Study

Authors
Chmura, SJ; Winter, K; Salama, JK; Robinson, CG; Pisansky, TM; Borges, V; Al-Hallaq, HA; Matuszak, MM; Park, SS; Gonzalez, VJ; Hasan, Y; Bazan, JG; Wong, P; Yoon, HA; Horton, JK; Gan, GN; Milano, MT; Sigurdson, ER; Moughan, J; White, JR
MLA Citation
Chmura, S. J., et al. “Phase I Trial of Stereotactic Body Radiation Therapy (SBRT) to Multiple Metastatic Sites: A NRG Oncology Study.” International Journal of Radiation Oncology*Biology*Physics, vol. 102, no. 3, Elsevier BV, 2018, pp. S68–69. Crossref, doi:10.1016/j.ijrobp.2018.06.187.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
102
Issue
3
Publish Date
2018
Start Page
S68
End Page
S69
DOI
10.1016/j.ijrobp.2018.06.187

Modeling and Prediction of SIB Prostate IMRT Plans

Authors
Vorren, K; Ge, Y; Kelley, MJ; Song, H; Wu, QRJ; Salama, JK
MLA Citation
Vorren, K., et al. “Modeling and Prediction of SIB Prostate IMRT Plans.” International Journal of Radiation Oncology*Biology*Physics, vol. 102, no. 3, Elsevier BV, 2018, pp. e541–e541. Crossref, doi:10.1016/j.ijrobp.2018.07.1512.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
102
Issue
3
Publish Date
2018
Start Page
e541
End Page
e541
DOI
10.1016/j.ijrobp.2018.07.1512

Patient Factors Predicting Intracranial Progression: Optimizing MRI Surveillance Interval Following Brain Metastases SRS

Authors
Natarajan, BD; Cummings, MA; Jutzy, J; Rushing, CN; Choudhury, KR; Moravan, MJ; Chmura, SJ; Milano, MT; Kirkpatrick, JP; Salama, JK
MLA Citation
Natarajan, B. D., et al. “Patient Factors Predicting Intracranial Progression: Optimizing MRI Surveillance Interval Following Brain Metastases SRS.” International Journal of Radiation Oncology*Biology*Physics, vol. 102, no. 3, Elsevier BV, 2018, pp. e308–e308. Crossref, doi:10.1016/j.ijrobp.2018.07.965.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
102
Issue
3
Publish Date
2018
Start Page
e308
End Page
e308
DOI
10.1016/j.ijrobp.2018.07.965

Stereotactic Body Radiation Therapy-Induced Abscopal Effect on Hepatocellular Carcinoma After Treatment for Lung Cancer: A Case Report.

Authors
Chino, F; Pollis, KE; Choi, S; Salama, JK; Palta, M
MLA Citation
Chino, Fumiko, et al. “Stereotactic Body Radiation Therapy-Induced Abscopal Effect on Hepatocellular Carcinoma After Treatment for Lung Cancer: A Case Report..” Hepatology, vol. 68, no. 4, Oct. 2018, pp. 1653–55. Pubmed, doi:10.1002/hep.30100.
PMID
29888796
Source
pubmed
Published In
Hepatology
Volume
68
Issue
4
Publish Date
2018
Start Page
1653
End Page
1655
DOI
10.1002/hep.30100

Postoperative Radiation Therapy for Prostate Cancer: Comparison of Conventional Versus Hypofractionated Radiation Regimens.

PURPOSE: To compare acute/late toxicity and biochemical control in contemporaneous prostate cancer patient cohorts treated with hypofractionated postprostatectomy radiation therapy (hypoPORT) or conventional PORT (coPORT). METHODS AND MATERIALS: Consecutive patients treated with intensity modulated hypoPORT (2.5 Gy per fraction, median cumulative dose 65 Gy [range, 57.5-70 Gy]) or coPORT (1.8-2.0 Gy per fraction, median cumulative dose 66 Gy [range, 60-74 Gy]) between 2005 and 2016 at 2 institutions constituted the study cohort. Acute toxicity and cumulative late grade 2 and ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity incidences were calculated for all patients using the Kaplan-Meier method and compared between cohorts. Biochemical progression-free survival (bPFS) was calculated in patients with ≥12 months' follow-up. RESULTS: Median follow-up for all 461 patients was 38.6 months. Of the 461 patients, 167 (36%) received hypoPORT, and 294 (64%) patients received coPORT. The hypoPORT cohort had significantly worse baseline urinary incontinence. Acute grade ≥2 GU toxicity was more common after hypoPORT (22% vs 8%) (P = .0001). Late grade ≥3 GU toxicity cumulative incidence at 6 years was 11% (hypoPORT) and 4% (coPORT) (P = .0081). However, hypoPORT was not associated with late grade ≥2 GU toxicity on multivariate analysis (hazard ratio 1.39, 95% confidence interval 0.86-2.34) (P = .18). There was no difference in acute or late GI toxicity. In the subset of patients with ≥12 month's follow-up (n = 364, median follow-up 52 months), 4-year bPFS was 78% (95% CI 69.4-85.0) after hypoPORT (P = .0038) and 65% (95% CI 57.6-71.1) after coPORT. HypoPORT was not significant for bPFS on multivariate analysis (hazard ratio 0.64, 95% CI 0.41-1.02, P = .059). CONCLUSIONS: HypoPORT shows promising early biochemical control. After controlling for baseline urinary function, hypoPORT was not associated with greater GU toxicity than coPORT. © 2018 Elsevier Inc.

Authors
Tandberg, DJ; Oyekunle, T; Lee, WR; Wu, Y; Salama, JK; Koontz, BF
MLA Citation
Tandberg, Daniel J., et al. “Postoperative Radiation Therapy for Prostate Cancer: Comparison of Conventional Versus Hypofractionated Radiation Regimens..” Int J Radiat Oncol Biol Phys, vol. 101, no. 2, June 2018, pp. 396–405. Pubmed, doi:10.1016/j.ijrobp.2018.02.002.
PMID
29559284
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
101
Issue
2
Publish Date
2018
Start Page
396
End Page
405
DOI
10.1016/j.ijrobp.2018.02.002

A randomized phase II study of anti-PD1 antibody [MK-3475 (Pembrolizumab)] alone versus anti-PD1 antibody plus stereotactic body radiation therapy in advanced merkel cell carcinoma (Alliance A091605).

Authors
Luke, JJ; Chmura, SJ; Allred, JB; Salama, JK; Al-Hallaq, HA; Hsu, C; Yom, SS; Kozloff, M; Munster, PN; Schwartz, GK
MLA Citation
Luke, Jason J., et al. “A randomized phase II study of anti-PD1 antibody [MK-3475 (Pembrolizumab)] alone versus anti-PD1 antibody plus stereotactic body radiation therapy in advanced merkel cell carcinoma (Alliance A091605)..” Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. TPS9599–TPS9599. Crossref, doi:10.1200/jco.2018.36.15_suppl.tps9599.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Issue
15_suppl
Publish Date
2018
Start Page
TPS9599
End Page
TPS9599
DOI
10.1200/jco.2018.36.15_suppl.tps9599

Improved survival of small cell lung cancer in the veterans health administration from 2000-2010: Association with increasing utilization of PET staging.

Authors
Hong, JC; Boyer, M; Spiegel, D; Williams, CD; Tong, BC; Shofer, S; Moravan, MJ; Kelley, MJ; Salama, JK
MLA Citation
Hong, Julian C., et al. “Improved survival of small cell lung cancer in the veterans health administration from 2000-2010: Association with increasing utilization of PET staging..” Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. e20571–e20571. Crossref, doi:10.1200/jco.2018.36.15_suppl.e20571.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Issue
15_suppl
Publish Date
2018
Start Page
e20571
End Page
e20571
DOI
10.1200/jco.2018.36.15_suppl.e20571

Role of adjuvant chemotherapy following chemoradiation and surgery for locoregionally advanced rectal cancer: A Veterans Health Administration analysis.

Authors
Spiegel, D; Boyer, M; Hong, JC; Williams, CD; Kelley, MJ; Rangwala, FA; Salama, JK; Palta, M
MLA Citation
Spiegel, Daphna, et al. “Role of adjuvant chemotherapy following chemoradiation and surgery for locoregionally advanced rectal cancer: A Veterans Health Administration analysis..” Journal of Clinical Oncology, vol. 36, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 741–741. Crossref, doi:10.1200/jco.2018.36.4_suppl.741.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Issue
4_suppl
Publish Date
2018
Start Page
741
End Page
741
DOI
10.1200/jco.2018.36.4_suppl.741

Managing Patients With Oligometastatic Non-Small-Cell Lung Cancer.

Metastatic lung cancer has long been considered incurable, with the goal of treatment being palliation. However, a clinically meaningful number of these patients with limited metastases (approximately 25%) are living long term after definitive treatment to all sites of active disease. These patients with so-called oligometastatic disease likely represent a distinct clinical group who may possess a more indolent biology compared with their more widely metastatic counterparts. Hellman and Weichselbaum proposed the existence of the oligometastatic state, on the basis of the spectrum theory of cancer spread. The literature suggests that an oligometastatic state exists in patients with non-small-cell lung cancer (NSCLC). This observation in the setting of rapidly evolving systemic therapies, including immune checkpoint inhibitors and an increasing number of targeted therapies, represents a unique clinical opportunity. Metastasis-directed therapies to address sites of disease include surgery (metastasectomy) and/or radiation therapy. Available evidence suggests that treating patients with limited or oligometastases may improve outcomes in a meaningful way; however, the majority of the randomized data includes patients with intracranial metastatic disease, and there are limited robust, randomized data available in the setting of NSCLC with only extracranial sites of metastatic disease. Ongoing randomized trials, including NRG-LU002 and the UK Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases trial, are aimed at evaluating this question further. One of the current limitations of aggressive treatment of oligometastatic NSCLC is the inability to accurately identify these patients before therapy, yet molecular markers, including microRNA profiles, are being investigated as a promising way to identify these patients.

Authors
Stephens, SJ; Moravan, MJ; Salama, JK
MLA Citation
Stephens, Sarah Jo, et al. “Managing Patients With Oligometastatic Non-Small-Cell Lung Cancer..” J Oncol Pract, vol. 14, no. 1, Jan. 2018, pp. 23–31. Pubmed, doi:10.1200/JOP.2017.026500.
PMID
29324212
Source
pubmed
Published In
J Oncol Pract
Volume
14
Issue
1
Publish Date
2018
Start Page
23
End Page
31
DOI
10.1200/JOP.2017.026500

Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis.

BACKGROUND: Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT). METHODS: Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors. RESULTS: 361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS. CONCLUSIONS: We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.

Authors
Hong, JC; Ayala-Peacock, DN; Lee, J; Blackstock, AW; Okunieff, P; Sung, MW; Weichselbaum, RR; Kao, J; Urbanic, JJ; Milano, MT; Chmura, SJ; Salama, JK
MLA Citation
Hong, Julian C., et al. “Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis..” Plos One, vol. 13, no. 4, 2018. Pubmed, doi:10.1371/journal.pone.0195149.
PMID
29649281
Source
pubmed
Published In
Plos One
Volume
13
Issue
4
Publish Date
2018
Start Page
e0195149
DOI
10.1371/journal.pone.0195149

Improved Survival of Stage I Non-Small Cell Lung Cancer: A VA Central Cancer Registry Analysis.

INTRODUCTION: The combined impact of advances in diagnosis and treatment of stage I NSCLC has not been assessed comprehensively. To define the survival impact of modern staging and treatment techniques for clinical stage I NSCLC, the Veterans Administration Central Cancer Registry, a database of U.S. veterans in whom the disease was diagnosed in the Veteran's Health Administration, was queried. From this database, patients who had stage I NSCLC diagnosed from 2001 to 2010 and were treated with either surgery or radiation were identified. METHODS: Overall survival (OS) and lung cancer-specific survival were determined. Propensity score matching and Cox multivariate analysis were used to adjust for baseline patient characteristics. RESULTS: A total of 11,997 patients were identified. The 4-year OS rate increased from 38.9% to 53.2% from 2001 to 2010 for all patients. Positron emission tomography and endobronchial ultrasound did not improve OS. Survival of radiated patients improved from 12.7% to 28.5%. The introduction of stereotactic body radiation therapy (SBRT) significantly improved OS (hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.54-0.68) and lung cancer-specific survival (HR = 0.39, 95% CI: 0.32-0.46) compared with conventionally fractionated radiation. The 4-year OS rate also improved after surgery (from 51.5% to 66.5%). This increase was associated with use of adjuvant chemotherapy, increased use of video-assisted thoracoscopic surgical procedures, and decreased pneumonectomy rates, with similar survival between open and video-assisted thoracoscopic surgical procedures. OS after lobectomy was superior to that after sublobar resection (HR = 0.82, 95% CI: 0.75-0.89). In the era of available SBRT (2008-2010), 4-year OS was not significantly different after sublobar resection or lobectomy for medically unfit patients (Charlson comorbidity index = 2) (55.4% and 58.1%, respectively; p = 0.69) but was significantly worse for fit patients (Charlson comorbidity index = 0-1) undergoing sublobar resection (55.5% and 68.0%, respectively; p < 0.001). OS (HR = 0.36, 95% CI: 0.35-0.38) and lung cancer-specific survival (HR = 0.31, 95% CI: 0.29-0.33) were improved after surgery as compared with after radiation, with the improvement maintained on matched comparison of lobectomy and SBRT. CONCLUSIONS: OS increased in veterans with a diagnosis of stage I NSCLC from 2001 to 2010; the increase was coincident with improved radiation and surgical techniques.

Authors
Boyer, MJ; Williams, CD; Harpole, DH; Onaitis, MW; Kelley, MJ; Salama, JK
MLA Citation
Boyer, Matthew J., et al. “Improved Survival of Stage I Non-Small Cell Lung Cancer: A VA Central Cancer Registry Analysis..” J Thorac Oncol, vol. 12, no. 12, Dec. 2017, pp. 1814–23. Pubmed, doi:10.1016/j.jtho.2017.09.1952.
PMID
28951090
Source
pubmed
Published In
J Thorac Oncol
Volume
12
Issue
12
Publish Date
2017
Start Page
1814
End Page
1823
DOI
10.1016/j.jtho.2017.09.1952

Metastasis-Directed Therapy: Right for Some, but Not All, and Not Here.

Authors
Moravan, MJ; Salama, JK
MLA Citation
Moravan, Michael J., and Joseph K. Salama. “Metastasis-Directed Therapy: Right for Some, but Not All, and Not Here..” Int J Radiat Oncol Biol Phys, vol. 99, no. 4, Nov. 2017. Pubmed, doi:10.1016/j.ijrobp.2017.03.047.
PMID
29063845
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
99
Issue
4
Publish Date
2017
Start Page
767
DOI
10.1016/j.ijrobp.2017.03.047

Triphasic contrast enhanced CT simulation with bolus tracking for pancreas SBRT target delineation.

Bolus-tracked multiphasic contrast computed tomography (CT) is often used in diagnostic radiology to enhance the visibility of pancreas tumors, but is uncommon in radiation therapy pancreas CT simulation, and its impact on gross tumor volume (GTV) delineation is unknown. This study evaluates the lesion conspicuity and consistency of pancreas stereotactic body radiation therapy (SBRT) GTVs contoured in the different contrast phases of triphasic CT simulation scans.Triphasic, bolus-tracked planning CT simulation scans of 10 consecutive pancreas SBRT patients were acquired, yielding images of the pancreas during the late arterial (LA), portal venous (PV), and either the early arterial or delayed phase. GTVs were contoured on each phase by a gastrointestinal-specialized radiation oncologist and reviewed by a fellowship-trained abdominal radiologist who specializes in pancreatic imaging. The volumes of the registered GTVs, their overlap ratio, and the 3-dimensional margin expansions necessary for each GTV to fully encompass GTVs from the other phases were calculated. The contrast difference between tumor and normal pancreas was measured, and 2 radiation oncologists rank-ordered the phases according to their value for the lesion-contouring task.Tumor-to-pancreas enhancement was on average much larger for the LA and PV than the delayed phase or early arterial phases; the LA and PV phases were also consistently preferred by the radiation oncologists. Enhancement differences among the phases resulted in highly variable GTV volumes with no observed trends. Overlap ratios ranged from 18% to 75% across all 3 phases, improving to 43% to 91% when considering only the preferred LA and PV phases. GTV expansions necessary to encompass all GTVs ranged from 0.3 to 1.8 cm for all 3 phases, improving slightly to 0.1 to 1.4 cm when considering just the LA and PV phases.For pancreas SBRT, we recommend combining the GTVs from a multiphasic CT simulation with bolus-tracking, including, at a minimum, a Boolean "OR" of the LA and PV phases.

Authors
Godfrey, DJ; Patel, BN; Adamson, JD; Subashi, E; Salama, JK; Palta, M
MLA Citation
Godfrey, Devon J., et al. “Triphasic contrast enhanced CT simulation with bolus tracking for pancreas SBRT target delineation..” Practical Radiation Oncology, vol. 7, no. 6, Nov. 2017, pp. e489–97. Epmc, doi:10.1016/j.prro.2017.04.008.
PMID
28666905
Source
epmc
Published In
Practical Radiation Oncology
Volume
7
Issue
6
Publish Date
2017
Start Page
e489
End Page
e497
DOI
10.1016/j.prro.2017.04.008

The Impact of Biologically Equivalent Dose on Tumor Control in Unresectable Hepatocellular Carcinoma

Authors
Stephens, SJ; Abdelazim, YA; Thomas, SM; Salama, JK; Godfrey, DJ; Willett, CG; Czito, B; Palta, M
MLA Citation
Stephens, S. J., et al. “The Impact of Biologically Equivalent Dose on Tumor Control in Unresectable Hepatocellular Carcinoma.” International Journal of Radiation Oncology*Biology*Physics, vol. 99, no. 2, Elsevier BV, 2017, pp. E188–89. Crossref, doi:10.1016/j.ijrobp.2017.06.1053.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
99
Issue
2
Publish Date
2017
Start Page
E188
End Page
E189
DOI
10.1016/j.ijrobp.2017.06.1053

Once Versus Twice Daily Fractionation for Limited Stage SCLC

Authors
Boyer, MJ; Willaims, CD; Kelley, MJ; Salama, JK
MLA Citation
Boyer, M. J., et al. “Once Versus Twice Daily Fractionation for Limited Stage SCLC.” International Journal of Radiation Oncology*Biology*Physics, vol. 99, no. 2, Elsevier BV, 2017, pp. E442–E442. Crossref, doi:10.1016/j.ijrobp.2017.06.1660.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
99
Issue
2
Publish Date
2017
Start Page
E442
End Page
E442
DOI
10.1016/j.ijrobp.2017.06.1660

Non-operative Management for Locally Advanced Rectal Cancer in the Veterans Health Administration

Authors
Spiegel, D; Boyer, MJ; Hong, JC; Willaims, CD; Kelley, MJ; Salama, JK; Palta, M
MLA Citation
Spiegel, D., et al. “Non-operative Management for Locally Advanced Rectal Cancer in the Veterans Health Administration.” International Journal of Radiation Oncology*Biology*Physics, vol. 99, no. 2, Elsevier BV, 2017, pp. S67–68. Crossref, doi:10.1016/j.ijrobp.2017.06.165.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
99
Issue
2
Publish Date
2017
Start Page
S67
End Page
S68
DOI
10.1016/j.ijrobp.2017.06.165

Toxicity and Biochemical Outcomes of Hypofractionated Intensity Modulated Post-Operative Radiation Therapy for Prostate Cancer

Authors
Tandberg, DJ; Lee, WR; Salama, JK; Koontz, BF
MLA Citation
Tandberg, D. J., et al. “Toxicity and Biochemical Outcomes of Hypofractionated Intensity Modulated Post-Operative Radiation Therapy for Prostate Cancer.” International Journal of Radiation Oncology*Biology*Physics, vol. 99, no. 2, Elsevier BV, 2017, pp. E267–E267. Crossref, doi:10.1016/j.ijrobp.2017.06.1241.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
99
Issue
2
Publish Date
2017
Start Page
E267
End Page
E267
DOI
10.1016/j.ijrobp.2017.06.1241

Predicting for Long-Term Survival in Oligometastatic Patients Treated With Ablative Radiation Therapy: A Multi-institutional Pooled Analysis

Authors
Hong, JC; Ayala-Peacock, DN; Lee, J; Blackstock, AW; Okunieff, P; Sung, M; Weichselbaum, RR; Kao, J; Urbanic, JJ; Milano, MT; Chmura, SJ; Salama, JK
MLA Citation
Hong, J. C., et al. “Predicting for Long-Term Survival in Oligometastatic Patients Treated With Ablative Radiation Therapy: A Multi-institutional Pooled Analysis.” International Journal of Radiation Oncology*Biology*Physics, vol. 99, no. 2, Elsevier BV, 2017, pp. S218–S218. Crossref, doi:10.1016/j.ijrobp.2017.06.537.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
99
Issue
2
Publish Date
2017
Start Page
S218
End Page
S218
DOI
10.1016/j.ijrobp.2017.06.537

Definitive Stereotactic Body Radiotherapy (SBRT) for Extracranial Oligometastases: An International Survey of >1000 Radiation Oncologists.

PURPOSE: Stereotactic body radiotherapy (SBRT) is often used to treat patients with oligometastases (OM). Yet, patterns of SBRT practice for OM are unknown. Therefore, we surveyed radiation oncologists internationally, to understand how and when SBRT is used for OM. METHODS: A 25-question survey was distributed to radiation oncologists. Respondents using SBRT for OM were asked how long they have been treating OM, number of patients treated, organs treated, primary reason for use, doses used, and future intentions. Respondents not using SBRT for OM were asked reasons why SBRT was not used and intentions for future adoption. Data were analyzed anonymously. RESULTS: We received 1007 surveys from 43 countries. Eighty-three percent began using SBRT after 2005 and greater than one third after 2010. Eighty-four percent cited perceived treatment response/durability as the primary reason for using SBRT in OM patients. Commonly treated organs were lung (90%), liver (75%), and spine (70%). SBRT dose/fractionation schemes varied widely. Most would offer a second course to new OM. Nearly all (99%) planned to continue and 66% planned to increase SBRT for OM. Of those not using SBRT, 59% plan to start soon. The most common reason for not using SBRT was lack of clinical efficacy (48%) or lack of necessary image guidance equipment (34%). CONCLUSIONS: Radiation oncologists are increasingly using SBRT for OM. The main reason for not using SBRT for OM is a perceived lack of evidence demonstrating clinical advantages. These data strengthen the need for robust prospective clinical trials (ongoing and in development) to demonstrate clinical efficacy given the widespread adoption of SBRT for OM.

Authors
Lewis, SL; Porceddu, S; Nakamura, N; Palma, DA; Lo, SS; Hoskin, P; Moghanaki, D; Chmura, SJ; Salama, JK
MLA Citation
Lewis, Stephen L., et al. “Definitive Stereotactic Body Radiotherapy (SBRT) for Extracranial Oligometastases: An International Survey of >1000 Radiation Oncologists..” Am J Clin Oncol, vol. 40, no. 4, Aug. 2017, pp. 418–22. Pubmed, doi:10.1097/COC.0000000000000169.
PMID
25647831
Source
pubmed
Published In
American Journal of Clinical Oncology
Volume
40
Issue
4
Publish Date
2017
Start Page
418
End Page
422
DOI
10.1097/COC.0000000000000169

Tolerability of veliparib (V) in combination with carboplatin (C)/paclitaxel (P): Based chemoradiotherapy (CRT) in subjects with stage III non-small cell lung cancer (NSCLC).

Authors
Kozono, DE; Salama, JK; Stinchcombe, T; Bogart, J; Petty, WJ; Guarino, MJ; Bazhenova, L; Larner, JM; Weiss, J; DiPetrillo, TA; Feigenberg, SJ; Xu, T; Hu, B; Nuthalapati, S; Rosenwinkel, L; Bensman, L; Johnson, EF; McKee, MD; Vokes, EE
MLA Citation
Kozono, David E., et al. “Tolerability of veliparib (V) in combination with carboplatin (C)/paclitaxel (P): Based chemoradiotherapy (CRT) in subjects with stage III non-small cell lung cancer (NSCLC)..” Journal of Clinical Oncology, vol. 35, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2017, pp. 8546–8546. Crossref, doi:10.1200/jco.2017.35.15_suppl.8546.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
35
Issue
15_suppl
Publish Date
2017
Start Page
8546
End Page
8546
DOI
10.1200/jco.2017.35.15_suppl.8546

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States.

BACKGROUND: Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer. METHODS: The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice. RESULTS: Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT. CONCLUSIONS: US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased patient convenience, and lower acute toxicity will increase the adoption of SC-RT by radiation oncologists in the United States. Cancer 2017;123:1434-1441. © 2016 American Cancer Society.

Authors
Mowery, YM; Salama, JK; Zafar, SY; Moore, HG; Willett, CG; Czito, BG; Hopkins, MB; Palta, M
MLA Citation
Mowery, Yvonne M., et al. “Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States..” Cancer, vol. 123, no. 8, Apr. 2017, pp. 1434–41. Pubmed, doi:10.1002/cncr.30461.
PMID
27984651
Source
pubmed
Published In
Cancer
Volume
123
Issue
8
Publish Date
2017
Start Page
1434
End Page
1441
DOI
10.1002/cncr.30461

ACR appropriateness criteria® nasal cavity and paranasal sinus cancers.

The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Here, we present the Appropriateness Criteria for cancers arising in the nasal cavity and paranasal sinuses (maxillary, sphenoid, and ethmoid sinuses). This includes clinical presentation, prognostic factors, principles of management, and treatment outcomes. Controversies regarding management of cervical lymph nodes are discussed. Rare and unusual nasal cavity cancers, such as esthesioneuroblastoma and sinonasal undifferentiated carcinomas, are included. © 2016 American College of Radiology. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 407-418, 2017.

Authors
Siddiqui, F; Smith, RV; Yom, SS; Beitler, JJ; Busse, PM; Cooper, JS; Hanna, EY; Jones, CU; Koyfman, SA; Quon, H; Ridge, JA; Saba, NF; Worden, F; Yao, M; Salama, JK; Expert Panel on Radiation Oncology - Head and Neck Cancer,
MLA Citation
Siddiqui, Farzan, et al. “ACR appropriateness criteria® nasal cavity and paranasal sinus cancers..” Head Neck, vol. 39, no. 3, Mar. 2017, pp. 407–18. Pubmed, doi:10.1002/hed.24639.
PMID
28032679
Source
pubmed
Published In
Head Neck
Volume
39
Issue
3
Publish Date
2017
Start Page
407
End Page
418
DOI
10.1002/hed.24639

A nomogram for testosterone recovery following combined androgen deprivation therapy and radiation therapy for prostate cancer.

Authors
Spiegel, D; Hong, JC; Lee, WR; Salama, JK
MLA Citation
Spiegel, Daphna, et al. “A nomogram for testosterone recovery following combined androgen deprivation therapy and radiation therapy for prostate cancer..” Journal of Clinical Oncology, vol. 35, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2017, pp. 67–67. Crossref, doi:10.1200/jco.2017.35.6_suppl.67.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
35
Issue
6_suppl
Publish Date
2017
Start Page
67
End Page
67
DOI
10.1200/jco.2017.35.6_suppl.67

Abstract OT1-04-06: NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer

Authors
Chmura, SJ; Winter, KA; Salama, JK; Woodward, WW; Borges, VF; Al-Hallaq, H; Martuszak, M; Jaskowiak, NT; Milano, MT; Bandos, H; White, JR
MLA Citation
Chmura, S. J., et al. “Abstract OT1-04-06: NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer.” Ongoing Clinical Trials, American Association for Cancer Research, 2017. Crossref, doi:10.1158/1538-7445.sabcs16-ot1-04-06.
Source
crossref
Published In
Ongoing Clinical Trials
Publish Date
2017
DOI
10.1158/1538-7445.sabcs16-ot1-04-06

Benchmark Credentialing Results for NRG-BR001: The First National Cancer Institute-Sponsored Trial of Stereotactic Body Radiation Therapy for Multiple Metastases.

PURPOSE: The NRG-BR001 trial is the first National Cancer Institute-sponsored trial to treat multiple (range 2-4) extracranial metastases with stereotactic body radiation therapy. Benchmark credentialing is required to ensure adherence to this complex protocol, in particular, for metastases in close proximity. The present report summarizes the dosimetric results and approval rates. METHODS AND MATERIALS: The benchmark used anonymized data from a patient with bilateral adrenal metastases, separated by <5 cm of normal tissue. Because the planning target volume (PTV) overlaps with organs at risk (OARs), institutions must use the planning priority guidelines to balance PTV coverage (45 Gy in 3 fractions) against OAR sparing. Submitted plans were processed by the Imaging and Radiation Oncology Core and assessed by the protocol co-chairs by comparing the doses to targets, OARs, and conformity metrics using nonparametric tests. RESULTS: Of 63 benchmarks submitted through October 2015, 94% were approved, with 51% approved at the first attempt. Most used volumetric arc therapy (VMAT) (78%), a single plan for both PTVs (90%), and prioritized the PTV over the stomach (75%). The median dose to 95% of the volume was 44.8 ± 1.0 Gy and 44.9 ± 1.0 Gy for the right and left PTV, respectively. The median dose to 0.03 cm3 was 14.2 ± 2.2 Gy to the spinal cord and 46.5 ± 3.1 Gy to the stomach. Plans that spared the stomach significantly reduced the dose to the left PTV and stomach. Conformity metrics were significantly better for single plans that simultaneously treated both PTVs with VMAT, intensity modulated radiation therapy, or 3-dimensional conformal radiation therapy compared with separate plans. No significant differences existed in the dose at 2 cm from the PTVs. CONCLUSIONS: Although most plans used VMAT, the range of conformity and dose falloff was large. The decision to prioritize either OARs or PTV coverage varied considerably, suggesting that the toxicity outcomes in the trial could be affected. Several benchmarks met the dose-volume histogram metrics but produced unacceptable plans owing to low conformity. Dissemination of a frequently-asked-questions document improved the approval rate at the first attempt. Benchmark credentialing was found to be a valuable tool for educating institutions about the protocol requirements.

Authors
Al-Hallaq, HA; Chmura, SJ; Salama, JK; Lowenstein, JR; McNulty, S; Galvin, JM; Followill, DS; Robinson, CG; Pisansky, TM; Winter, KA; White, JR; Xiao, Y; Matuszak, MM
MLA Citation
Al-Hallaq, Hania A., et al. “Benchmark Credentialing Results for NRG-BR001: The First National Cancer Institute-Sponsored Trial of Stereotactic Body Radiation Therapy for Multiple Metastases..” Int J Radiat Oncol Biol Phys, vol. 97, no. 1, Jan. 2017, pp. 155–63. Pubmed, doi:10.1016/j.ijrobp.2016.09.030.
PMID
27843033
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
97
Issue
1
Publish Date
2017
Start Page
155
End Page
163
DOI
10.1016/j.ijrobp.2016.09.030

Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer.

BACKGROUND: Patients with limited metastases, oligometastases (OMs), might have improved outcomes compared with patients with widespread distant metastases (DMs). The incidence and behavior of OMs from non-small-cell lung cancer (NSCLC) need further characterization. PATIENTS AND METHODS: The medical records of patients who had undergone surgery for stage I-III NSCLC from 1995 to 2009 were retrospectively reviewed. All information pertaining to development of the first metastatic progression was recorded and analyzed. Patients with DMs were categorized into OMs (1-3 lesions potentially amenable to local therapy) and DM subgroups. RESULTS: Of 1719 patients reviewed, 368 (21%) developed DMs with a median follow-up period of 39 months. A single lesion was diagnosed in 115 patients (31%) and 69 (19%) had 2 to 3 lesions (50% oligometastatic). The median survival from the DM diagnosis for oligometastatic and diffuse DM was 12.4 and 6.1 months, respectively (hazard ratio, 0.54; 95% confidence interval, 0.42-0.68; P < .001). Patients with a single metastasis had the longest median survival at 14.7 months. Younger age, OM, the use of chemotherapy for the primary tumor, and DM detection by surveillance imaging were independently associated with improved survival. CONCLUSION: DMs and OMs are common in surgically managed NSCLC. Overall survival appears to be prolonged with OM.

Authors
Torok, JA; Gu, L; Tandberg, DJ; Wang, X; Harpole, DH; Kelsey, CR; Salama, JK
MLA Citation
Torok, Jordan A., et al. “Patterns of Distant Metastases After Surgical Management of Non-Small-cell Lung Cancer..” Clin Lung Cancer, vol. 18, no. 1, Jan. 2017, pp. e57–70. Pubmed, doi:10.1016/j.cllc.2016.06.011.
PMID
27477488
Source
pubmed
Published In
Clin Lung Cancer
Volume
18
Issue
1
Publish Date
2017
Start Page
e57
End Page
e70
DOI
10.1016/j.cllc.2016.06.011

The expanding role of stereotactic body radiation therapy in oligometastatic solid tumors: What do we know and where are we going?

The spectrum hypothesis posits that there are distinct clinical states of metastatic progression. Early data suggest that aggressive treatment of more biologically indolent metastatic disease, characterized by metastases limited in number and destination organ, may offer an opportunity to alter the disease course, potentially allowing for longer survival, delay of systemic therapy, or even cure. The development of stereotactic body radiation therapy (SBRT) has opened new avenues for the treatment of oligometastatic disease. Early data support the use of SBRT for treating oligometastases in a number of organs, with promising rates of treated metastasis control and overall survival. Ongoing investigation is required to definitively establish benefit, determine the appropriate treatment regimen, refine patient selection, and incorporate SBRT with systemic therapies.

Authors
Hong, JC; Salama, JK
MLA Citation
Hong, Julian C., and Joseph K. Salama. “The expanding role of stereotactic body radiation therapy in oligometastatic solid tumors: What do we know and where are we going?.” Cancer Treat Rev, vol. 52, Jan. 2017, pp. 22–32. Pubmed, doi:10.1016/j.ctrv.2016.11.003.
PMID
27886588
Source
pubmed
Published In
Cancer Treat Rev
Volume
52
Publish Date
2017
Start Page
22
End Page
32
DOI
10.1016/j.ctrv.2016.11.003

Radiotherapy for Oligometastatic Lung Cancer.

Non-small cell lung cancer (NSCLC) typically presents at an advanced stage, which is often felt to be incurable, and such patients are usually treated with a palliative approach. Accumulating retrospective and prospective clinical evidence, including a recently completed randomized trial, support the existence of an oligometastatic disease state wherein select individuals with advanced NSCLC may experience historically unprecedented prolonged survival with aggressive local treatments, consisting of radiotherapy and/or surgery, to limited sites of metastatic disease. This is reflected in the most recent AJCC staging subcategorizing metastatic disease into intra-thoracic (M1a), a single extra thoracic site (M1b), and more diffuse metastases (M1c). In the field of radiation oncology, recent technological advances have allowed for the delivery of very high, potentially ablative, doses of radiotherapy to both intra- and extra-cranial disease sites, referred to as stereotactic radiosurgery and stereotactic body radiotherapy (or SABR), in much shorter time periods compared to conventional radiation and with minimal associated toxicity. At the same time, significant improvements in systemic therapy, including platinum-based doublet chemotherapy, molecular agents targeting oncogene-addicted NSCLC, and immunotherapy in the form of checkpoint inhibitors, have led to improved control of micro-metastatic disease and extended survival sparking newfound interest in combining these agents with ablative local therapies to provide additive, and in the case of radiation and immunotherapy, potentially synergistic, effects in order to further improve progression-free and overall survival. Currently, despite the tantalizing potential associated with aggressive local therapy in the setting of oligometastatic NSCLC, well-designed prospective randomized controlled trials sufficiently powered to detect and measure the possible added benefit afforded by this approach are desperately needed.

Authors
Bergsma, DP; Salama, JK; Singh, DP; Chmura, SJ; Milano, MT
MLA Citation
Bergsma, Derek P., et al. “Radiotherapy for Oligometastatic Lung Cancer..” Front Oncol, vol. 7, 2017. Pubmed, doi:10.3389/fonc.2017.00210.
PMID
28975081
Source
pubmed
Published In
Frontiers in Oncology
Volume
7
Publish Date
2017
Start Page
210
DOI
10.3389/fonc.2017.00210

Is a single isocenter sufficient for volumetric modulated arc therapy radiosurgery when multiple itracranial metastases are spatially dispersed?

Previous work demonstrated improved dosimetry of single isocenter volumetric modulated arc therapy (VMAT) of multiple intracranial targets when they are located ≤ 4cm from isocenter because of narrower multileaf collimators (MLCs). In follow-up, we sought to determine if decreasing isocenter-target distance (diso) by using 2 to 3 isocenters would improve dosimetry for spatially dispersed targets. We also investigated the effect of a maximum dose constraint during VMAT optimization, and the dosimetric effect of the number of VMAT arcs used for a larger number of targets (i.e., 7 to 9). We identified radiosurgery cases that had multiple intracranial targets with diso of at least 1 target > 5cm. A single isocenter VMAT plan was created using a standardized 4-arc technique with 18Gy per target. Each case was then replanned (1) using 2 to 3 isocenters, (2) including a maximum dose constraint per target, and in the case of 7 to 9 targets, (3) using 3 to 6 arcs. Dose evaluation included brain V6Gy and V12Gy, and conformity index (CI), gradient index (GI), and heterogeneity index (HI) per target. Two isocenters were sufficient to limit diso to ≤ 4cm and ≤ 5cm for 11/15 and 13/15 cases, respectively; after replanning with 2 to 3 isocenters, diso decreased from 5.8 ± 2.8cm (2.3 14.9) to 2.5 ± 1.4cm (0 5.2). All dose statistics improved on average, albeit modestly: V6Gy = 6.9 ± 7.1%, V12Gy = 0.9% ± 4.4%, CI = 2.6% ± 4.6%, GI = 0.9% ± 12.7%, and HI = 2.6% ± 5.2%; however, the number of arcs doubled and monitor units increase by nearly 2-fold. A maximum dose constraint had a negative effect on all dose indices, increasing V12Gy by 9.7 ± 6.9%. For ≥ 7 targets, increasing number of arcs to > 3 improved CI, V12Gy, and V6Gy. A single isocenter is likely sufficient for VMAT radiosurgery of multiple intracranial metastases. Optimal treatment plan quality is achieved when no constraint is placed on the maximum target dose; for cases with many targets at least 4 arcs are needed for optimal plan quality.

Authors
Morrison, J; Hood, R; Yin, F-F; Salama, JK; Kirkpatrick, J; Adamson, J
MLA Citation
Morrison, Jay, et al. “Is a single isocenter sufficient for volumetric modulated arc therapy radiosurgery when multiple itracranial metastases are spatially dispersed?.” Medical Dosimetry : Official Journal of the American Association of Medical Dosimetrists, vol. 41, no. 4, Dec. 2016, pp. 285–89. Epmc, doi:10.1016/j.meddos.2016.06.007.
PMID
27614790
Source
epmc
Published In
Medical Dosimetry
Volume
41
Issue
4
Publish Date
2016
Start Page
285
End Page
289
DOI
10.1016/j.meddos.2016.06.007

Rationale of technical requirements for NRG-BR001: The first NCI-sponsored trial of SBRT for the treatment of multiple metastases.

INTRODUCTION: In 2014, the NRG Oncology Group initiated the first National Cancer Institute-sponsored, phase 1 clinical trial of stereotactic body radiation therapy (SBRT) for the treatment of multiple metastases in multiple organ sites (BR001; NCT02206334). The primary endpoint is to test the safety of SBRT for the treatment of 2 to 4 multiple lesions in several anatomic sites in a multi-institutional setting. Because of the technical challenges inherent to treating multiple lesions as their spatial separation decreases, we present the technical requirements for NRG-BR001 and the rationale for their selection. METHODS AND MATERIALS: Patients with controlled primary tumors of breast, non-small cell lung, or prostate are eligible if they have 2 to 4 metastases distributed among 7 extracranial anatomic locations throughout the body. Prescription and organ-at-risk doses were determined by expert consensus. Credentialing requirements include (1) irradiation of the Imaging and Radiation Oncology Core phantom with SBRT, (2) submitting image guided radiation therapy case studies, and (3) planning the benchmark. Guidelines for navigating challenging planning cases including assessing composite dose are discussed. RESULTS: Dosimetric planning to multiple lesions receiving differing doses (45-50 Gy) and fractionation (3-5) while irradiating the same organs at risk is discussed, particularly for metastases in close proximity (≤5 cm). The benchmark case was selected to demonstrate the planning tradeoffs required to satisfy protocol requirements for 2 nearby lesions. Examples of passing benchmark plans exhibited a large variability in plan conformity. DISCUSSION: NRG-BR001 was developed using expert consensus on multiple issues from the dose fractionation regimen to the minimum image guided radiation therapy guidelines. Credentialing was tied to the task rather than the anatomic site to reduce its burden. Every effort was made to include a variety of delivery methods to reflect current SBRT technology. Although some simplifications were adopted, the successful completion of this trial will inform future designs of both national and institutional trials and would allow immediate clinical adoption of SBRT trials for oligometastases.

Authors
Al-Hallaq, HA; Chmura, S; Salama, JK; Winter, KA; Robinson, CG; Pisansky, TM; Borges, V; Lowenstein, JR; McNulty, S; Galvin, JM; Followill, DS; Timmerman, RD; White, JR; Xiao, Y; Matuszak, MM
MLA Citation
Al-Hallaq, Hania A., et al. “Rationale of technical requirements for NRG-BR001: The first NCI-sponsored trial of SBRT for the treatment of multiple metastases..” Pract Radiat Oncol, vol. 6, no. 6, Nov. 2016, pp. e291–98. Pubmed, doi:10.1016/j.prro.2016.05.004.
PMID
27345129
Source
pubmed
Published In
Pract Radiat Oncol
Volume
6
Issue
6
Publish Date
2016
Start Page
e291
End Page
e298
DOI
10.1016/j.prro.2016.05.004

Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome.

PURPOSE: To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy. METHODS AND MATERIALS: We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration associated with radiation therapy of 5 daily fractions (7.5, 9, or 13.5 Gy/d) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiation therapy. Oxygen saturation and total hemoglobin concentration were computed using an inverse Monte Carlo model. RESULTS: First, oxygenation kinetics during and after radiation therapy, but before tumor volumes changed, were associated with local tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiation therapy (days 12-15) compared with tumors that recurred locally. Second, within the group of tumors that recurred, faster increases in oxygenation during radiation therapy (day 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operating characteristic curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. Third, the rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/d did not initiate an increase in oxygenation, whereas 13.5 Gy/d triggered significant increases in oxygenation during and after radiation therapy. CONCLUSIONS: Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiation therapy.

Authors
Hu, F; Vishwanath, K; Salama, JK; Erkanli, A; Peterson, B; Oleson, JR; Lee, WT; Brizel, DM; Ramanujam, N; Dewhirst, MW
MLA Citation
Hu, Fangyao, et al. “Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome..” Int J Radiat Oncol Biol Phys, vol. 96, no. 2, Oct. 2016, pp. 462–69. Pubmed, doi:10.1016/j.ijrobp.2016.06.007.
PMID
27598811
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Issue
2
Publish Date
2016
Start Page
462
End Page
469
DOI
10.1016/j.ijrobp.2016.06.007

Radiation Oncologists' Practice Patterns and Attitudes Regarding Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer in the United States.

Authors
Mowery, YM; Salama, JK; Zafar, SY; Moore, HG; Willett, CG; Czito, B; Hopkins, MB; Palta, M
MLA Citation
Mowery, Y. M., et al. “Radiation Oncologists' Practice Patterns and Attitudes Regarding Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer in the United States..” Int J Radiat Oncol Biol Phys, vol. 96, no. 2S, Oct. 2016. Pubmed, doi:10.1016/j.ijrobp.2016.06.505.
PMID
27675787
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Issue
2S
Publish Date
2016
Start Page
S203
DOI
10.1016/j.ijrobp.2016.06.505

Survival With Stereotactic Body Radiation Therapy (SBRT) and Conventional Radiation Therapy (CRT) in Stage I Non-Small Cell Lung Cancer Patients in the Veterans Affairs System.

Authors
Boyer, MJ; Williams, C; Kelley, MJ; Salama, JK
MLA Citation
Boyer, M. J., et al. “Survival With Stereotactic Body Radiation Therapy (SBRT) and Conventional Radiation Therapy (CRT) in Stage I Non-Small Cell Lung Cancer Patients in the Veterans Affairs System..” Int J Radiat Oncol Biol Phys, vol. 96, no. 2S, Oct. 2016. Pubmed, doi:10.1016/j.ijrobp.2016.06.037.
PMID
27676046
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Issue
2S
Publish Date
2016
Start Page
S9
DOI
10.1016/j.ijrobp.2016.06.037

Feasibility of Delivered Radiation Dose Using Cone Beam Computed Tomography as a Secondary Endpoint in a Phase 1 Trial of MOSART Stereotactic Body Radiation Therapy and Pembrolizumab for Metastatic Solid Tumors.

Authors
Lemons, JM; Chmura, SJ; Luke, JJ; Salama, JK; Al-Hallaq, HA
MLA Citation
Lemons, J. M., et al. “Feasibility of Delivered Radiation Dose Using Cone Beam Computed Tomography as a Secondary Endpoint in a Phase 1 Trial of MOSART Stereotactic Body Radiation Therapy and Pembrolizumab for Metastatic Solid Tumors..” Int J Radiat Oncol Biol Phys, vol. 96, no. 2S, Oct. 2016, pp. E631–32. Pubmed, doi:10.1016/j.ijrobp.2016.06.2209.
PMID
27675212
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Issue
2S
Publish Date
2016
Start Page
E631
End Page
E632
DOI
10.1016/j.ijrobp.2016.06.2209

Toxicity and Survival for Metastatic Melanoma Patients Treated With Anti-PD1 Therapy and Radiation Treatment.

Authors
Mowery, YM; Patel, K; Olson, AC; Khan, MK; Salama, JK; Salama, AK
MLA Citation
Mowery, Y. M., et al. “Toxicity and Survival for Metastatic Melanoma Patients Treated With Anti-PD1 Therapy and Radiation Treatment..” Int J Radiat Oncol Biol Phys, vol. 96, no. 2S, Oct. 2016, pp. S158–59. Pubmed, doi:10.1016/j.ijrobp.2016.06.383.
PMID
27675668
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Issue
2S
Publish Date
2016
Start Page
S158
End Page
S159
DOI
10.1016/j.ijrobp.2016.06.383

The Use of Reirradiation in Locally Recurrent, Nonmetastatic Rectal Cancer.

Authors
Susko, M; Lee, J; Salama, JK; Thomas, S; Uronis, H; Hsu, D; Migaly, J; Willett, CG; Czito, B; Palta, M
MLA Citation
Susko, M., et al. “The Use of Reirradiation in Locally Recurrent, Nonmetastatic Rectal Cancer..” Int J Radiat Oncol Biol Phys, vol. 96, no. 2S, Oct. 2016, pp. E192–93. Pubmed, doi:10.1016/j.ijrobp.2016.06.1076.
PMID
27674024
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Issue
2S
Publish Date
2016
Start Page
E192
End Page
E193
DOI
10.1016/j.ijrobp.2016.06.1076

Survival With Stereotactic Body Radiation Therapy (SBRT) and Conventional Radiation Therapy (CRT) in Stage I Non-Small Cell Lung Cancer Patients in the Veterans Affairs System

Authors
Boyer, MJ; Williams, C; Kelley, MJ; Salama, JK
MLA Citation
Boyer, M. J., et al. “Survival With Stereotactic Body Radiation Therapy (SBRT) and Conventional Radiation Therapy (CRT) in Stage I Non-Small Cell Lung Cancer Patients in the Veterans Affairs System.” International Journal of Radiation Oncology Biology Physics, vol. 96, no. 2, 2016, pp. S9–S9.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
S9
End Page
S9

Hippocampal Dose From Stereotactic Radiosurgery for 4 to 10 Brain Metastases: Risk Factors and Feasibility of Dose Reduction Via Reoptimization

Authors
Birer, SR; Olson, AC; Adamson, J; Kim, GJ; Salama, JK; Kirkpatrick, JP
MLA Citation
Birer, S. R., et al. “Hippocampal Dose From Stereotactic Radiosurgery for 4 to 10 Brain Metastases: Risk Factors and Feasibility of Dose Reduction Via Reoptimization.” International Journal of Radiation Oncology Biology Physics, vol. 96, no. 2, 2016, pp. E608–09.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
E608
End Page
E609

Toxicity and Survival for Metastatic Melanoma Patients Treated With Anti-PD1 Therapy and Radiation Treatment

Authors
Mowery, YM; Patel, K; Olson, AC; Khan, MK; Salama, JK; Salama, AK
MLA Citation
Mowery, Y. M., et al. “Toxicity and Survival for Metastatic Melanoma Patients Treated With Anti-PD1 Therapy and Radiation Treatment.” International Journal of Radiation Oncology Biology Physics, vol. 96, no. 2, 2016, pp. S158–59.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
S158
End Page
S159

Feasibility of Delivered Radiation Dose Using Cone Beam Computed Tomography as a Secondary Endpoint in a Phase 1 Trial of MOSART Stereotactic Body Radiation Therapy and Pembrolizumab for Metastatic Solid Tumors

Authors
Lemons, JM; Chmura, SJ; Luke, JJ; Salama, JK; Al-Hallaq, HA
MLA Citation
Lemons, J. M., et al. “Feasibility of Delivered Radiation Dose Using Cone Beam Computed Tomography as a Secondary Endpoint in a Phase 1 Trial of MOSART Stereotactic Body Radiation Therapy and Pembrolizumab for Metastatic Solid Tumors.” International Journal of Radiation Oncology Biology Physics, vol. 96, no. 2, 2016, pp. E631–32.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
E631
End Page
E632

Radiation Oncologists' Practice Patterns and Attitudes Regarding Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer in the United States

Authors
Mowery, YM; Salama, JK; Zafar, SY; Moore, HG; Willett, CG; Czito, B; Hopkins, MB; Palta, M
MLA Citation
Mowery, Y. M., et al. “Radiation Oncologists' Practice Patterns and Attitudes Regarding Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer in the United States.” International Journal of Radiation Oncology Biology Physics, vol. 96, no. 2, 2016, pp. S203–S203.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2
Publish Date
2016
Start Page
S203
End Page
S203

The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer.

BACKGROUND: The optimal approach to patients with locally recurrent, non-metastatic rectal cancer is unclear. This study evaluates the outcomes and toxicity associated with pelvic re-irradiation. METHODS: Patients undergoing re-irradiation for locally recurrent, non-metastatic, rectal cancer between 2000 and 2014 were identified. Acute and late toxicities were assessed using common terminology criteria for adverse events version 4.0. Disease-related endpoints included palliation of local symptoms, surgical outcomes, and local progression-free survival (PFS), distant PFS and overall survival (OS) using the Kaplan-Meier method. RESULTS: Thirty-three patients met the criteria for inclusion in this study. Two (6 %) experienced early grade 3+ toxicity and seven (21 %) experienced late grade 3+ toxicity. Twenty-three patients presented with symptomatic local recurrence and 18 (78 %) reported symptomatic relief. Median local PFS was 8.7 (95 % CI 3.8-15.2) months, with a 2-year rate of 15.7 % (4.1-34.2), and median time to distant progression was 4.4 (2.2-33.3) months, with a 2-year distant PFS rate of 38.9 % (20.1-57.3). Median OS time for patients was 23.1 (11.1-33.0) months. Of the 14 patients who underwent surgery, median survival was 32.3 (13.8-48.0) months compared with 13.3 (2.2-33.0) months in patients not undergoing surgery (p = 0.10). A margin-negative (R0) resection was achieved in 10 (71 %) of the surgeries. Radiation treatment modality (intensity-modulated radiation therapy, three-dimensional conformal radiotherapy, intraoperative radiation therapy) did not influence local or distant PFS or OS. CONCLUSION: Re-irradiation is a beneficial treatment modality for the management of locally recurrent, non-metastatic rectal cancer. It is associated with symptom improvement, low rates of toxicity, and similar benefits among radiation modalities.

Authors
Susko, M; Lee, J; Salama, J; Thomas, S; Uronis, H; Hsu, D; Migaly, J; Willett, C; Czito, B; Palta, M
MLA Citation
Susko, Matthew, et al. “The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer..” Ann Surg Oncol, vol. 23, no. 11, Oct. 2016, pp. 3609–15. Pubmed, doi:10.1245/s10434-016-5250-z.
PMID
27169769
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
23
Issue
11
Publish Date
2016
Start Page
3609
End Page
3615
DOI
10.1245/s10434-016-5250-z

Impact of Race on Treatment and Survival among U.S. Veterans with Early-Stage Lung Cancer.

INTRODUCTION: Numerous reports suggest lower rates of surgical procedures and poorer survival for black patients with early-stage (stage I or II) NSCLC than for white patients. This study examined treatment trends among blacks and whites with early-stage NSCLC and determined whether racial disparities exist in survival among patients receiving similar treatment. METHODS: A retrospective analysis of 18,466 patients in the Veteran Affairs Central Cancer Registry in whom stage I or II NSCLC was diagnosed in 2001-2010 was conducted. Patients were categorized as receiving an operation, radiation, or other/no treatment. Overall survival (OS) and lung cancer-specific survival (LCSS) were evaluated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: There was a statistically significant disparity between black and white patients receiving an operation that decreased over time to similar rates (p = 0.01). No significant racial differences in receipt of radiation were noted. Race was not associated with OS among all patients (hazard ratio [HR] = 0.97, 95% confidence interval [CI]: 0.93-1.02). Among patients who received an operation, no racial difference in OS was observed (HR = 0.94, 95% CI: 0.87-1.01), but the HR for blacks versus whites was 0.90 (95% CI: 0.82-0.98) for radiation treatment and 0.89 (95% CI: 0.81-0.97) for other/no treatment. Race was not associated with LCSS among all patients combined or within each treatment category. CONCLUSIONS: A racial disparity in the rate of operation was no longer apparent at the end of the study period. There was no racial difference in OS or LCSS among all patients in this equal access health care system. Long-documented racial differences in lung cancer treatment and mortality result from disparity of access to health care and delivery of recommended treatment.

Authors
Williams, CD; Salama, JK; Moghanaki, D; Karas, TZ; Kelley, MJ
MLA Citation
Williams, Christina D., et al. “Impact of Race on Treatment and Survival among U.S. Veterans with Early-Stage Lung Cancer..” J Thorac Oncol, vol. 11, no. 10, Oct. 2016, pp. 1672–81. Pubmed, doi:10.1016/j.jtho.2016.05.030.
PMID
27296104
Source
pubmed
Published In
J Thorac Oncol
Volume
11
Issue
10
Publish Date
2016
Start Page
1672
End Page
1681
DOI
10.1016/j.jtho.2016.05.030

Hippocampal Dose From Stereotactic Radiosurgery for 4 to 10 Brain Metastases: Risk Factors and Feasibility of Dose Reduction Via Reoptimization.

Authors
Birer, SR; Olson, AC; Adamson, J; Kim, GJ; Salama, JK; Kirkpatrick, JP
MLA Citation
Birer, S. R., et al. “Hippocampal Dose From Stereotactic Radiosurgery for 4 to 10 Brain Metastases: Risk Factors and Feasibility of Dose Reduction Via Reoptimization..” International Journal of Radiation Oncology, Biology, Physics, vol. 96, no. 2S, Oct. 2016, pp. E608–09. Epmc, doi:10.1016/j.ijrobp.2016.06.2153.
PMID
27675151
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E608
End Page
E609
DOI
10.1016/j.ijrobp.2016.06.2153

Triphasic Bolus Tracking Computed Tomography Simulation for Stereotactic Body Radiation Therapy of Locoregionally Advanced Pancreatic Cancer.

Authors
Godfrey, DJ; Patel, BN; Adamson, J; Salama, JK; Palta, M
MLA Citation
Godfrey, D. J., et al. “Triphasic Bolus Tracking Computed Tomography Simulation for Stereotactic Body Radiation Therapy of Locoregionally Advanced Pancreatic Cancer..” International Journal of Radiation Oncology, Biology, Physics, vol. 96, no. 2S, Oct. 2016, pp. E200–01. Epmc, doi:10.1016/j.ijrobp.2016.06.1095.
PMID
27674047
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
96
Issue
2S
Publish Date
2016
Start Page
E200
End Page
E201
DOI
10.1016/j.ijrobp.2016.06.1095

Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab.

PURPOSE: Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination. METHODS AND MATERIALS: We reviewed the records of consecutive patients with unresectable stage 3 or 4 melanoma treated with ipilimumab. Patients were categorized as having received RT or not. Differences were estimated between these 2 cohorts. RESULTS: We identified 88 patients treated with ipilimumab. At baseline, the ipilimumab-plus-RT group (n=44) had more unfavorable characteristics. Despite this, overall survival, progression-free survival, and both immune-related and non-immune-related toxicity were not statistically different (P=.67). Patients who received ipilimumab before RT had an increased duration of irradiated tumor response compared with patients receiving ipilimumab after RT (74.7% vs 44.8% at 12 months; P=.01, log-rank test). In addition, patients receiving ablative RT had non-statistically significantly improved median overall survival (19.6 vs 10.2 months), as well as 6-month (95.1% vs 72.7%) and 12-month (79.7% vs 48.5%) survival rates, compared with those treated with conventionally fractionated RT. CONCLUSIONS: We found that both ablative and conventionally fractionated RT can be safely administered with ipilimumab without a clinically apparent increase in toxicity. Patients who received ipilimumab before RT had an increased duration of irradiated tumor response.

Authors
Qin, R; Olson, A; Singh, B; Thomas, S; Wolf, S; Bhavsar, NA; Hanks, BA; Salama, JK; Salama, AKS
MLA Citation
Qin, Rosie, et al. “Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab..” Int J Radiat Oncol Biol Phys, vol. 96, no. 1, Sept. 2016, pp. 72–77. Pubmed, doi:10.1016/j.ijrobp.2016.04.017.
PMID
27375168
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Issue
1
Publish Date
2016
Start Page
72
End Page
77
DOI
10.1016/j.ijrobp.2016.04.017

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer.

PURPOSE: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. METHODS AND MATERIALS: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. RESULTS: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. CONCLUSIONS: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation.

Authors
Seiwert, TY; Melotek, JM; Blair, EA; Stenson, KM; Salama, JK; Witt, ME; Brisson, RJ; Chawla, A; Dekker, A; Lingen, MW; Kocherginsky, M; Villaflor, VM; Cohen, EEW; Haraf, DJ; Vokes, EE
MLA Citation
Seiwert, Tanguy Y., et al. “Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer..” Int J Radiat Oncol Biol Phys, vol. 96, no. 1, Sept. 2016, pp. 21–29. Pubmed, doi:10.1016/j.ijrobp.2016.04.030.
PMID
27511844
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Issue
1
Publish Date
2016
Start Page
21
End Page
29
DOI
10.1016/j.ijrobp.2016.04.030

ACR Appropriateness Criteria(®) Locoregional therapy for resectable oropharyngeal squamous cell carcinomas.

BACKGROUND: There are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations. Ongoing investigations are examining deintensified treatments for human papillomavirus (HPV)-associated oropharyngeal SCC. METHODS: The Appropriateness Criteria panel, using modified Delphi methodology, produced a literature summary, an assessment of treatment recommendations, and cases to illustrate their use. RESULTS: A multidisciplinary team produces optimum results. Based on HPV status, smoking history, and staging, patients are divided into groups at low, intermediate, and high-risk of death. In the future, treatment recommendations may be influenced by HPV status, which has changed the epidemiology of oropharyngeal SCC. CONCLUSION: T1 to T2N0M0 resectable oropharyngeal SCC can be treated with surgery or radiation without chemotherapy. Patients with T1-2N1-2aM0 disease can receive radiation, chemoradiation, or transoral surgery with neck dissection and appropriate adjuvant therapy. Patients with T1-2N2b-3M0 disease should receive chemoradiation or transoral surgery with neck dissection and appropriate adjuvant therapy. Concurrent chemoradiation is preferred for T3 to T4 disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1299-1309, 2016.

Authors
Beitler, JJ; Quon, H; Jones, CU; Salama, JK; Busse, PM; Cooper, JS; Koyfman, SA; Ridge, JA; Saba, NF; Siddiqui, F; Smith, RV; Worden, F; Yao, M; Yom, SS; Expert Panel on Radiation Oncology - Head and Neck,
MLA Citation
Beitler, Jonathan J., et al. “ACR Appropriateness Criteria(®) Locoregional therapy for resectable oropharyngeal squamous cell carcinomas..” Head Neck, vol. 38, no. 9, Sept. 2016, pp. 1299–309. Pubmed, doi:10.1002/hed.24447.
PMID
27330003
Source
pubmed
Published In
Head Neck
Volume
38
Issue
9
Publish Date
2016
Start Page
1299
End Page
1309
DOI
10.1002/hed.24447

Outcomes and toxicity of stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab.

Purpose: Patients with melanoma treated with ipilimumab and radiosurgery (stereotactic radiosurgery [SRS]) were reviewed for efficacy/safety. Methods: Patients who received ipilimumab and SRS for brain metastases were analyzed for control of SRS-treated metastasis and overall survival. Results: We identified 27 patients, 26 were assessable for outcomes. Median time-to-treated metastasis progression was 6.3 months (95% CI: 3.1-12.2). Overall survival was 23.4 months (95% CI: 5.7-not estimable) for SRS prior to/during ipilimumab (n = 14), and 10.4 months (95% CI: 1.9-not estimable) for SRS after ipilimumab (n = 12). Overall, no unexpected toxicities were seen: 11% of patients experienced grade 3 CNS toxicity and 7% developed radionecrosis. Conclusion: SRS for melanoma brain metastases with ipilimumab was well-tolerated. There may be improved survival for patients receiving SRS prior to/during ipilimumab.

Authors
Olson, AC; Thomas, S; Qin, R; Singh, B; Salama, JK; Kirkpatrick, J; Salama, AK
MLA Citation
Olson, Adam C., et al. “Outcomes and toxicity of stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab..” Melanoma Manag, vol. 3, no. 3, Sept. 2016, pp. 177–86. Pubmed, doi:10.2217/mmt-2016-0004.
PMID
30190887
Source
pubmed
Published In
Melanoma Manag
Volume
3
Issue
3
Publish Date
2016
Start Page
177
End Page
186
DOI
10.2217/mmt-2016-0004

Treatment of Thymoma-Associated Myasthenia Gravis With Stereotactic Body Radiotherapy: A Case Report.

Authors
Lee, CM; Lee, JD; Hobson-Webb, LD; Bedlack, RS; Salama, JK
MLA Citation
Lee, Caroline M., et al. “Treatment of Thymoma-Associated Myasthenia Gravis With Stereotactic Body Radiotherapy: A Case Report..” Ann Intern Med, vol. 165, no. 4, Aug. 2016, pp. 300–01. Pubmed, doi:10.7326/L15-0469.
PMID
26974367
Source
pubmed
Published In
Ann Intern Med
Volume
165
Issue
4
Publish Date
2016
Start Page
300
End Page
301
DOI
10.7326/L15-0469

Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer.

To determine the feasibility and toxicity of radiation therapy, delivered either as definitive treatment or following surgery, following neo-adjuvant immune checkpoint inhibition for locally advanced NSCLC sixteen patients who received neo-adjuvant chemotherapy including ipilimumab as part of a phase II study were identified. Patients were analyzed by intent of radiation and toxicity graded based on CTCAE 4.0. There were seven patients identified who received definitive radiation and nine who received post-operative radiation. There was no grade 3 or greater toxicity in the definitive treatment group although one patient stopped treatment early due to back pain secondary to progression outside of the treatment field. In the post-operative treatment group, one patient required a one week break due to grade 2 odynophagia and no grade 3 or greater toxicity was observed. In this study of radiation as definitive or post-operative treatment following neo-adjuvant chemotherapy including ipilimumab for locally advanced NSCLC was feasible and well tolerated with limited toxicity.

Authors
Boyer, MJ; Gu, L; Wang, X; Kelsey, CR; Yoo, DS; Onaitis, MW; Dunphy, FR; Crawford, J; Ready, NE; Salama, JK
MLA Citation
Boyer, Matthew J., et al. “Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer..” Lung Cancer, vol. 98, Aug. 2016, pp. 76–78. Pubmed, doi:10.1016/j.lungcan.2016.05.014.
PMID
27393510
Source
pubmed
Published In
Lung Cancer
Volume
98
Publish Date
2016
Start Page
76
End Page
78
DOI
10.1016/j.lungcan.2016.05.014

A Multidisciplinary Approach to Larynx Cancer: One Size Does Not Fit All.

Authors
Mowery, YM; Salama, JK
MLA Citation
Mowery, Yvonne M., and Joseph K. Salama. “A Multidisciplinary Approach to Larynx Cancer: One Size Does Not Fit All..” J Oncol Pract, vol. 12, no. 8, Aug. 2016, pp. 725–26. Pubmed, doi:10.1200/JOP.2016.014803.
PMID
27511719
Source
pubmed
Published In
J Oncol Pract
Volume
12
Issue
8
Publish Date
2016
Start Page
725
End Page
726
DOI
10.1200/JOP.2016.014803

Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT).

BACKGROUND: The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases. METHODS: Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS. RESULTS: Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available. CONCLUSIONS: A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242-50. © 2016 American Cancer Society.

Authors
Wong, AC; Watson, SP; Pitroda, SP; Son, CH; Das, LC; Stack, ME; Uppal, A; Oshima, G; Khodarev, NN; Salama, JK; Weichselbaum, RR; Chmura, SJ
MLA Citation
Wong, Anthony C., et al. “Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT)..” Cancer, vol. 122, no. 14, July 2016, pp. 2242–50. Pubmed, doi:10.1002/cncr.30058.
PMID
27206146
Source
pubmed
Published In
Cancer
Volume
122
Issue
14
Publish Date
2016
Start Page
2242
End Page
2250
DOI
10.1002/cncr.30058

ACR Appropriateness criteria® for nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) presents mostly with locally advanced disease and is treated with multimodal therapy; however, consensus is lacking for different clinical scenarios. METHODS: The American College of Radiology (ACR) Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. RESULTS: The ACR Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for guiding management of nasopharyngeal carcinoma. CONCLUSION: Multidisciplinary evaluation is essential to guiding the optimal use of surgery, radiation, and systemic therapy in this disease. © 2015 Wiley Periodicals, Inc. Head Neck 38: 979-986, 2016.

Authors
Saba, NF; Salama, JK; Beitler, JJ; Busse, PM; Cooper, JS; Jones, CU; Koyfman, S; Quon, H; Ridge, JA; Siddiqui, F; Worden, F; Yao, M; Yom, SS; Expert Panel on Radiation Oncology-Head and Neck Cancer,
MLA Citation
Saba, Nabil F., et al. “ACR Appropriateness criteria® for nasopharyngeal carcinoma..” Head Neck, vol. 38, no. 7, July 2016, pp. 979–86. Pubmed, doi:10.1002/hed.24423.
PMID
27131050
Source
pubmed
Published In
Head Neck
Volume
38
Issue
7
Publish Date
2016
Start Page
979
End Page
986
DOI
10.1002/hed.24423

Surgery versus stereotactic body radiation therapy for operable stage I non-small cell lung cancer: Can we achieve equipoise?

Authors
Onaitis, MW; Salama, J
MLA Citation
Onaitis, Mark W., and Joseph Salama. “Surgery versus stereotactic body radiation therapy for operable stage I non-small cell lung cancer: Can we achieve equipoise?.” J Thorac Cardiovasc Surg, vol. 152, no. 1, July 2016, pp. 1–2. Pubmed, doi:10.1016/j.jtcvs.2016.04.016.
PMID
27343902
Source
pubmed
Published In
The Journal of Thoracic and Cardiovascular Surgery
Volume
152
Issue
1
Publish Date
2016
Start Page
1
End Page
2
DOI
10.1016/j.jtcvs.2016.04.016

Stereotactic Body Radiotherapy for Oligometastasis: Opportunities for Biology to Guide Clinical Management.

Oligometastasis refers to a state of limited metastatic disease burden, in which surgical or ablative treatment to all known visible metastases holds promise to extend survival or even effect cure. Stereotactic body radiotherapy is a form of radiation treatment capable of delivering a high biologically effective dose of radiation in a highly conformal manner, with a favorable toxicity profile. Enthusiasm for oligometastasis ablation, however, should be counterbalanced against the limited supporting evidence. It remains unknown to what extent (if any) ablation influences survival or quality of life. Rising clinical equipoise necessitates the completion of randomized controlled trials to assess this, several of which are underway. However, a lack of clear identification criteria or biomarkers to define the oligometastatic state hampers optimal patient selection.This narrative review explores the evolutionary origins of oligometastasis, the steps of the metastatic process at which oligometastases may arise, and the biomolecular mediators of this state. It discusses clinical outcomes with treatment of oligometastases, ongoing trials, and areas of basic and translational research that may lead to novel biomarkers. These efforts should provide a clearer, biomolecular definition of oligometastatic disease and aid in the accurate selection of patients for ablative therapies.

Authors
Correa, RJM; Salama, JK; Milano, MT; Palma, DA
MLA Citation
Correa, Rohann J. M., et al. “Stereotactic Body Radiotherapy for Oligometastasis: Opportunities for Biology to Guide Clinical Management..” Cancer J, vol. 22, no. 4, July 2016, pp. 247–56. Pubmed, doi:10.1097/PPO.0000000000000202.
PMID
27441744
Source
pubmed
Published In
Cancer J
Volume
22
Issue
4
Publish Date
2016
Start Page
247
End Page
256
DOI
10.1097/PPO.0000000000000202

Irradiation and immunotherapy: From concept to the clinic.

In recent years, an increased understanding of T-cell-regulatory mechanisms has led to the development of a novel class of immune-checkpoint inhibitors that have robust clinical activity against a broad array of malignancies-even those that historically were not believed to be sensitive to immune therapy. With this, there has been renewed interest in the potential for synergy with more traditional forms of anticancer therapy like radiation therapy (RT). The role of RT in palliation or as definitive treatment for certain malignancies has been well established. Yet, in recent years, the concept has come to light that RT could be an attractive partner for use in combination with other immunotherapies. The effects of RT include not only control of an irradiated tumor but also multiple immunomodulatory effects on both the tumor and the microenvironment, priming tumors for an immune-mediated response. Herein, the authors summarize relevant preclinical data and rationale supporting the synergy of combined RT and immunotherapy and highlight recent clinical work on promising combination strategies. Cancer 2016;122:1659-71. © 2016 American Cancer Society.

Authors
Salama, AKS; Postow, MA; Salama, JK
MLA Citation
Salama, April K. S., et al. “Irradiation and immunotherapy: From concept to the clinic..” Cancer, vol. 122, no. 11, June 2016, pp. 1659–71. Pubmed, doi:10.1002/cncr.29889.
PMID
26914620
Source
pubmed
Published In
Cancer
Volume
122
Issue
11
Publish Date
2016
Start Page
1659
End Page
1671
DOI
10.1002/cncr.29889

Stereotactic body radiotherapy for oligometastatic breast cancer: a new standard of care, or a medical reversal in waiting?

Metastases-directed therapy via surgery or stereotactic body radiotherapy (SBRT) has become the de facto standard of care in the United States and abroad despite a lack of high quality prospective, randomized trials. Oligometastatic tumors may behave in an inherently more indolent manner secondary to underlying biologic characteristics, including discrepant microRNA expression patterns. This biologic discrepancy suggests that historic improvements in survival observed in retrospective series may stem from the inherent biology of oligometastases and selection biases as opposed to advances in novel localized treatments. In this review, we discuss the theoretical basis for metastases-directed therapies, retrospective data supporting these approaches, recent advances in oligometastasis biology, and ongoing prospective randomized trials designed to compare SBRT and standard of care systemic therapies. We focus on metastases-directed therapy, primarily SBRT, for oligometastatic breast cancer with references to other tumor types when these other tumor types inform oligometastatic breast cancer treatment.

Authors
Drazer, MW; Salama, JK; Hahn, OM; Weichselbaum, RR; Chmura, SJ
MLA Citation
Drazer, Michael W., et al. “Stereotactic body radiotherapy for oligometastatic breast cancer: a new standard of care, or a medical reversal in waiting?.” Expert Rev Anticancer Ther, vol. 16, no. 6, June 2016, pp. 625–32. Pubmed, doi:10.1080/14737140.2016.1178577.
PMID
27078719
Source
pubmed
Published In
Expert Rev Anticancer Ther
Volume
16
Issue
6
Publish Date
2016
Start Page
625
End Page
632
DOI
10.1080/14737140.2016.1178577

NRG BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical ablation for newly oligometastatic breast cancer.

Authors
Chmura, SJ; Winter, KA; Salama, JK; Woodward, WA; Borges, VF; Al-Hallaq, HA; Matuszak, M; Jaskowiak, NT; Milano, MT; Bandos, H; White, JR
MLA Citation
Chmura, Steven J., et al. “NRG BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical ablation for newly oligometastatic breast cancer..” Journal of Clinical Oncology, vol. 34, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2016, pp. TPS1098–TPS1098. Crossref, doi:10.1200/jco.2016.34.15_suppl.tps1098.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
34
Issue
15_suppl
Publish Date
2016
Start Page
TPS1098
End Page
TPS1098
DOI
10.1200/jco.2016.34.15_suppl.tps1098

Physics considerations for single-isocenter, volumetric modulated arc radiosurgery for treatment of multiple intracranial targets.

OBJECTIVE: Our purpose was to address challenges associated with single-isocenter radiosurgery for multiple intracranial targets (SIRMIT) including increased sensitivity to rotational uncertainties (resulting from distance of the targets from isocenter) as well as potential for decreased plan quality from larger multileaf collimator width >4 cm from isocenter. METHODS AND MATERIALS: We evaluated the effect that a 6 degrees-of-freedom couch correction had on localization uncertainty for SIRMIT using thermoplastic mask immobilization. Required setup margin was determined from rotation of the skull and mask (setup kV cone beam computed tomography relative to planning computed tomography). Intraoperational margin was determined from skull rotation within the mask (difference between pre- and posttreatment cone beam computed tomography). We also investigated 4 isocenter placement strategies: volume centroid, centroid of equally weighted points (1 per target), centroid of points weighted by inverse of volume, and Eclipse's built-in method. RESULTS: When no 6 degrees-of-freedom couch correction is performed after initial setup, a 0.35-mm margin is required per centimeter of target-isocenter separation to account for 95% of rotational uncertainties at initial setup. This margin is reduced to 0.10 mm/cm of target-isocenter separation to account for intraoperative rotational uncertainties when the initial setup uncertainty is eliminated via image guided 6 degrees-of-freedom couch correction. Analysis of 11 multitarget plans (37 targets) showed that conformity index and gradient index improved with decreasing distance from isocenter, this trend being more pronounced for targets <1 mL. Alternative isocenters aimed at decreasing distance of small targets improved their gradient index, but resulted in poorer dose indices for large targets. Mean distance from isocenter was smallest for the centroid of equally weighted points (4.1 ± 1.6cm vs 4.2-4.5cm). CONCLUSIONS: Rotational corrections via image guidance are necessary for SIRMIT with a thermoplastic mask for immobilization. There is a clear tradeoff between dosimetric quality of small and large targets that should be considered carefully when placing the isocenter.

Authors
Stanhope, C; Chang, Z; Wang, Z; Yin, F-F; Kim, G; Salama, JK; Kirkpatrick, J; Adamson, J
MLA Citation
Stanhope, Carl, et al. “Physics considerations for single-isocenter, volumetric modulated arc radiosurgery for treatment of multiple intracranial targets..” Pract Radiat Oncol, vol. 6, no. 3, 2016, pp. 207–13. Pubmed, doi:10.1016/j.prro.2015.10.010.
PMID
26723551
Source
pubmed
Published In
Pract Radiat Oncol
Volume
6
Issue
3
Publish Date
2016
Start Page
207
End Page
213
DOI
10.1016/j.prro.2015.10.010

In Reply to Fiorino and Cozzarini.

Authors
Lewis, SL; Patel, PR; Palta, M; Yoo, DS; Salama, JK
MLA Citation
Lewis, Stephen L., et al. “In Reply to Fiorino and Cozzarini..” Int J Radiat Oncol Biol Phys, vol. 94, no. 4, Mar. 2016, pp. 860–61. Pubmed, doi:10.1016/j.ijrobp.2016.01.009.
PMID
26972661
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
94
Issue
4
Publish Date
2016
Start Page
860
End Page
861
DOI
10.1016/j.ijrobp.2016.01.009

Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer.

PURPOSE: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. METHODS AND MATERIALS: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. RESULTS: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). CONCLUSIONS: The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.

Authors
Lewis, SL; Patel, P; Song, H; Freedland, SJ; Bynum, S; Oh, D; Palta, M; Yoo, D; Oleson, J; Salama, JK
MLA Citation
Lewis, Stephen L., et al. “Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer..” Int J Radiat Oncol Biol Phys, vol. 94, no. 3, Mar. 2016, pp. 605–11. Pubmed, doi:10.1016/j.ijrobp.2015.11.025.
PMID
26867889
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
94
Issue
3
Publish Date
2016
Start Page
605
End Page
611
DOI
10.1016/j.ijrobp.2015.11.025

Positive Interaction between Prophylactic Cranial Irradiation and Maintenance Sunitinib for Untreated Extensive-Stage Small Cell Lung Cancer Patients After Standard Chemotherapy: A Secondary Analysis of CALGB 30504 (ALLIANCE).

BACKGROUND: Prophylactic cranial irradiation (PCI) has become a standard option for patients with extensive-stage small cell lung cancer (ES-SCLC). The Cancer and Leukemia Group B 30504 trial was a randomized phase II study of the effect of sunitinib versus placebo in ES-SCLC patients responding to platinum-based systemic therapy. The study required preenrollment brain imaging. PCI was provided at the discretion of treating physicians. We performed a secondary analysis of the Cancer and Leukemia Group B trial to determine the impact of PCI on patients with ES-SCLC. METHODS: Fisher's exact test and the Wilcoxon rank-sum test were conducted to identify the differences between patients receiving PCI and patients not receiving PCI. Kaplan-Meier analyses described progression-free survival (PFS) and overall survival (OS) for patients in the PCI and non-PCI groups. RESULTS: A total of 85 patients received maintenance therapy (41 received placebo and 44 received sunitinib). Patient characteristics were balanced between the PCI and non-PCI groups. The patients receiving PCI plus sunitinib had a nonsignificant 2.7-month improvement in PFS (5.0 months versus 2.3 months, p = 0.14, hazard risk [HR] = 0.62, 95% confidence interval [CI]: 0.33-1.18) trending toward improved OS (8.9 months versus 5.4 months, p = 0.053, HR = 0.47, 95% CI: 0.22-1.03). PCI was associated with a trend toward improved median PFS (2.9 months versus 2.2 months, p = 0.096, HR = 0.69, 95% CI: 0.45-1.07) but not median OS (8.3 months in the PCI group versus 8.7 months in the non-PCI group, p = 0.76, HR = 1.07, 95% CI: 0.67-1.71). The patients receiving placebo had no improvement in PFS or OS with PCI. CONCLUSIONS: Trends toward improved PFS and OS were seen in patients receiving PCI and sunitinib, thus supporting the need for further prospective research evaluating the integration of maintenance systemic therapy and PCI for patients with ES-SCLC. Improved outcomes for patients with ES-SCLC after induction chemotherapy may require PCI, thoracic radiotherapy, and maintenance systemic therapy to achieve control of both intracranial and extracranial disease.

Authors
Salama, JK; Gu, L; Wang, X; Pang, HH; Bogart, JA; Crawford, J; Schild, SE; Vokes, EE; Ready, NE
MLA Citation
Salama, Joseph K., et al. “Positive Interaction between Prophylactic Cranial Irradiation and Maintenance Sunitinib for Untreated Extensive-Stage Small Cell Lung Cancer Patients After Standard Chemotherapy: A Secondary Analysis of CALGB 30504 (ALLIANCE)..” J Thorac Oncol, vol. 11, no. 3, Mar. 2016, pp. 361–69. Pubmed, doi:10.1016/j.jtho.2015.11.001.
PMID
26723241
Source
pubmed
Published In
J Thorac Oncol
Volume
11
Issue
3
Publish Date
2016
Start Page
361
End Page
369
DOI
10.1016/j.jtho.2015.11.001

Abstract OT3-03-04: NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer

Authors
Chmura, SJ; Winter, KA; Salama, JK; Woodward, WA; Borges, VF; Al-Hallaq, H; Matuszak, M; Jaskowiak, NT; Milano, MT; Bandos, H; White, JR
MLA Citation
Chmura, S. J., et al. “Abstract OT3-03-04: NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer.” Ongoing Clinical Trials, American Association for Cancer Research, 2016. Crossref, doi:10.1158/1538-7445.sabcs15-ot3-03-04.
Source
crossref
Published In
Ongoing Clinical Trials
Publish Date
2016
DOI
10.1158/1538-7445.sabcs15-ot3-03-04

Ablative Approaches for Pulmonary Metastases.

Pulmonary metastases are common in patients with cancer for which surgery is considered a standard approach in appropriately selected patients. A number of patients are not candidates for surgery due to a medical comorbidities or the extent of surgery required. For these patients, noninvasive or minimally invasive approaches to ablate pulmonary metastases are potential treatment strategies. This article summarizes the rationale and outcomes for non-surgical treatment approaches, including radiotherapy, radiofrequency and microwave ablation, for pulmonary metastases.

Authors
Boyer, MJ; Ricardi, U; Ball, D; Salama, JK
MLA Citation
Boyer, Matthew J., et al. “Ablative Approaches for Pulmonary Metastases..” Thorac Surg Clin, vol. 26, no. 1, Feb. 2016, pp. 19–34. Pubmed, doi:10.1016/j.thorsurg.2015.09.004.
PMID
26611507
Source
pubmed
Published In
Thorac Surg Clin
Volume
26
Issue
1
Publish Date
2016
Start Page
19
End Page
34
DOI
10.1016/j.thorsurg.2015.09.004

ACR Appropriateness Criteria(®) Aggressive Nonmelanomatous Skin Cancer of the Head and Neck.

BACKGROUND: Aggressive nonmelanomatous skin cancer (NMSC) of the head and neck presents an increasingly common therapeutic challenge for which prospective clinical trials are lacking. METHODS: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. RESULTS: The American College of Radiology Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for guiding management of aggressive NMSC. CONCLUSION: Multidisciplinary assessment is vital to guiding the ideal use of surgery, radiation, and systemic therapy in this disease.

Authors
Koyfman, SA; Cooper, JS; Beitler, JJ; Busse, PM; Jones, CU; McDonald, MW; Quon, H; Ridge, JA; Saba, NF; Salama, JK; Siddiqui, F; Smith, RV; Worden, F; Yao, M; Yom, SS
MLA Citation
Koyfman, Shlomo A., et al. “ACR Appropriateness Criteria(®) Aggressive Nonmelanomatous Skin Cancer of the Head and Neck..” Head Neck, vol. 38, no. 2, Feb. 2016, pp. 175–82. Pubmed, doi:10.1002/hed.24171.
PMID
26791005
Source
pubmed
Published In
Head Neck
Volume
38
Issue
2
Publish Date
2016
Start Page
175
End Page
182
DOI
10.1002/hed.24171

Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors.

Authors
Hong, JC; Salama, JK
MLA Citation
Hong, Julian C., and Joseph K. Salama. “Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?.” Transl Lung Cancer Res, vol. 5, no. 1, Feb. 2016, pp. 126–33. Pubmed, doi:10.3978/j.issn.2218-6751.2016.01.07.
PMID
26958507
Source
pubmed
Published In
Translational Lung Cancer Research
Volume
5
Issue
1
Publish Date
2016
Start Page
126
End Page
133
DOI
10.3978/j.issn.2218-6751.2016.01.07

Radiosurgery for Brain Metastases in Melanoma Patients Receiving Ipilimumab

Authors
Olson, AC; Qin, R; Singh, B; Bhavsar, N; Wolf, S; Salama, JK; Kirkpatrick, JP; Salama, AK
MLA Citation
Olson, A. C., et al. “Radiosurgery for Brain Metastases in Melanoma Patients Receiving Ipilimumab.” International Journal of Radiation Oncology*Biology*Physics, vol. 93, no. 3, Elsevier BV, 2015, pp. E88–E88. Crossref, doi:10.1016/j.ijrobp.2015.07.771.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E88
End Page
E88
DOI
10.1016/j.ijrobp.2015.07.771

Long-term Survivors of an SBRT Dose-Escalation Study for Oligometastases: Clinical and Molecular Markers

Authors
Wong, AC; Pitroda, S; Watson, S; Son, C; Das, LC; Uppal, A; Oshima, G; Stack, M; Khodarev, N; Salama, JK; Posner, M; Weichselbaum, RR; Chmura, SJ
MLA Citation
Wong, A. C., et al. “Long-term Survivors of an SBRT Dose-Escalation Study for Oligometastases: Clinical and Molecular Markers.” International Journal of Radiation Oncology*Biology*Physics, vol. 93, no. 3, Elsevier BV, 2015, pp. S64–S64. Crossref, doi:10.1016/j.ijrobp.2015.07.152.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
S64
End Page
S64
DOI
10.1016/j.ijrobp.2015.07.152

Benchmark Credentialing Results for the First Multiple Metastases SBRT Protocol: NRG BR001

Authors
Al-Hallaq, HA; Chmura, SJ; Salama, JK; Leif, JL; McNulty, S; Galvin, JM; Followill, DS; Robinson, CG; White, JR; Xiao, Y; Matuszak, MM
MLA Citation
Al-Hallaq, H. A., et al. “Benchmark Credentialing Results for the First Multiple Metastases SBRT Protocol: NRG BR001.” International Journal of Radiation Oncology*Biology*Physics, vol. 93, no. 3, Elsevier BV, 2015, pp. S85–86. Crossref, doi:10.1016/j.ijrobp.2015.07.205.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
S85
End Page
S86
DOI
10.1016/j.ijrobp.2015.07.205

PCI Survival Improvement for Extensive Stage SCLC Limited to Patients on Maintenance Systemic Therapy: A Secondary Analysis of CALGB 30504

Authors
Salama, JK; Gu, L; Wang, X; Bogart, J; Crawford, J; Schild, S; Ready, N; Vokes, E
MLA Citation
Salama, Joseph K., et al. “PCI Survival Improvement for Extensive Stage SCLC Limited to Patients on Maintenance Systemic Therapy: A Secondary Analysis of CALGB 30504.” Journal of Thoracic Oncology, vol. 10, no. 9, ELSEVIER SCIENCE INC, Sept. 2015, pp. S401–S401.
Source
wos
Published In
Journal of Thoracic Oncology
Volume
10
Issue
9
Publish Date
2015
Start Page
S401
End Page
S401

Improved Survival in Patients with Stage I-II NSCLC Treated with Surgery or Radiotherapy in the Department of Veterans Affairs

Authors
Salama, JK; Williams, CD; Moghanaki, D; Kelley, MJ
MLA Citation
Salama, Joseph K., et al. “Improved Survival in Patients with Stage I-II NSCLC Treated with Surgery or Radiotherapy in the Department of Veterans Affairs.” Journal of Thoracic Oncology, vol. 10, no. 9, ELSEVIER SCIENCE INC, Sept. 2015, pp. S280–81.
Source
wos
Published In
Journal of Thoracic Oncology
Volume
10
Issue
9
Publish Date
2015
Start Page
S280
End Page
S281

Radiation therapy for oligometastatic non-small cell lung cancer.

Interest has been increasing in the treatment of non-small cell lung cancer (NSCLC) patients with limited or oligometastatic disease. Surgery has historically been used to remove non-small cell lung cancer metastases, but recent developments including advanced radiotherapy planning and delivery techniques, often called stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR), has been associated with high rates of treated metastasis control. Therefore, given common comorbid disease, often precluding surgery, an increasing number of oligometastatic NSCLC patients are receiving radiation for ablation of all disease. Early results have reported favorable survival for some, with improved median survival, and approximately 25 % alive long term. Patients with fewer metastases, those treated to all known cancerous sites, and longer disease-free intervals tend to have better outcomes. While promising, better clinical criteria are needed to optimize patient selection. The biologic underpinnings of the oligometastatic state are beginning to be demonstrated with specific microRNAs being associated with limited or no progression both in human samples and murine models. Clinical trials are ongoing to improve the techniques used to deliver radiotherapy for NSCLC oligometastases. Ideally, randomized studies will need to be conducted to demonstrate the utility of these treatments suggested by the uncontrolled studies to date. In lieu of these, data presented here may help guide clinicians as to appropriate patient selection.

Authors
Salama, JK; Schild, SE
MLA Citation
Salama, Joseph K., and Steven E. Schild. “Radiation therapy for oligometastatic non-small cell lung cancer..” Cancer Metastasis Rev, vol. 34, no. 2, June 2015, pp. 183–93. Pubmed, doi:10.1007/s10555-015-9559-z.
PMID
25948377
Source
pubmed
Published In
Cancer Metastasis Rev
Volume
34
Issue
2
Publish Date
2015
Start Page
183
End Page
193
DOI
10.1007/s10555-015-9559-z

NRG BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical ablation for newly oligometastatic breast cancer.

Authors
Chmura, SJ; Winter, KA; Salama, JK; Woodward, WA; Borges, VF; Al-Hallaq, HA; Matuszak, M; Jaskowiak, NT; Milano, MT; Bandos, H; White, JR
MLA Citation
Chmura, Steven J., et al. “NRG BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical ablation for newly oligometastatic breast cancer..” Journal of Clinical Oncology, vol. 33, no. 15, AMER SOC CLINICAL ONCOLOGY, 2015. Wos, doi:10.1200/jco.2015.33.15_suppl.tps1105.
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015
DOI
10.1200/jco.2015.33.15_suppl.tps1105

Prophylactic cranial irradiation in elderly patients with small cell lung cancer: findings from a North Central Cancer Treatment Group pooled analysis.

OBJECTIVES: To examine the efficacy of prophylactic cranial irradiation (PCI) in elderly patients with small cell lung cancer (SCLC) (≥70 years of age) from a pooled analysis of four prospective trials. MATERIALS & METHODS: One hundred fifty-five patients with SCLC (limited stage, LSCLC, and extensive stage, ESCLC) participated in four phase II or III trials. Ninety-one patients received PCI (30 Gy/15 or 25 Gy/10) and 64 patients did not receive PCI. Survival was compared in a landmark analysis that included only patients who had stable disease or better in response to primary therapy. RESULTS: Patients who received PCI had better survival than patients who did not receive PCI (median survival 12.0 months vs. 7.6 months, 3-year overall survival 13.2% vs. 3.1%, HR = 0.53 [95% CI 0.36-0.78], p = 0.001). On multivariate analysis of the entire cohort, the only factor that remained significant for survival was stage (ESCLC vs. LSCLC, p = 0.0072). In contrast, the multivariate analysis of patients who had ESCLC revealed that PCI was the sole factor associated with a survival advantage (HR = 0.47 [95% CI 0.24-0.93], p = 0.03). Grade 3 or higher adverse events (AEs) were significantly greater in patients who received PCI (71.4% vs. 47.5%, p = 0.0031), with non-neuro and non-heme being the specific AE categories most strongly correlated with PCI delivery. CONCLUSIONS: PCI was associated with a significant improvement in survival for our entire elderly SCLC patient cohort on univariate analysis. Multivariate analysis suggested that the survival advantage remained significant in patients with ESCLC. PCI was also associated with a modest increase in grade 3 or higher AEs.

Authors
Rule, WG; Foster, NR; Meyers, JP; Ashman, JB; Vora, SA; Kozelsky, TF; Garces, YI; Urbanic, JJ; Salama, JK; Schild, SE
MLA Citation
Rule, William G., et al. “Prophylactic cranial irradiation in elderly patients with small cell lung cancer: findings from a North Central Cancer Treatment Group pooled analysis..” J Geriatr Oncol, vol. 6, no. 2, Mar. 2015, pp. 119–26. Pubmed, doi:10.1016/j.jgo.2014.11.002.
PMID
25482023
Source
pubmed
Published In
J Geriatr Oncol
Volume
6
Issue
2
Publish Date
2015
Start Page
119
End Page
126
DOI
10.1016/j.jgo.2014.11.002

Radical prostatectomy versus radiation therapy: can pretreatment nomograms be used to select the appropriate prostate cancer treatment?

Authors
Simon, RM; Salama, JK; Freedland, SJ
MLA Citation
Simon, Ross M., et al. “Radical prostatectomy versus radiation therapy: can pretreatment nomograms be used to select the appropriate prostate cancer treatment?.” Eur Urol, vol. 67, no. 2, Feb. 2015, pp. 210–11. Pubmed, doi:10.1016/j.eururo.2014.10.009.
PMID
25457494
Source
pubmed
Published In
Eur Urol
Volume
67
Issue
2
Publish Date
2015
Start Page
210
End Page
211
DOI
10.1016/j.eururo.2014.10.009

The multidisciplinary management 11 of early stage cervical esophageal cancer

© Springer International Publishing Switzerland 2015. Cancer development in the cervical portion of the esophagus presents a unique challenge to management given the close proximity of critical structures in the head and neck. Cervical esophageal cancer (CEC) was historically approached with primarysurgery, pharyngo-laryngo-esophagectomy (PLE), but a paradigm shift has occurred suchthat functional organ preservation with concurrent chemotherapy and radiation (CRT)isnow preferred. This chapter will review anatomical considerations pertinent to themanagement of CEC as well as the risk factors and multidisciplinary treatment approach to this disease.

Authors
Salama, JK; Palta, M; Torok, JA
MLA Citation
Salama, J. K., et al. “The multidisciplinary management 11 of early stage cervical esophageal cancer.” Esophageal Cancer: Prevention, Diagnosis and Therapy, 2015, pp. 173–85. Scopus, doi:10.1007/978-3-319-20068-2_11.
Source
scopus
Publish Date
2015
Start Page
173
End Page
185
DOI
10.1007/978-3-319-20068-2_11

Stereotactic treatment for oligometastatic breast cancer

© Springer International Publishing Switzerland, 2016. Although uncommon, a small number of patients with radiographically evident and/or biopsy-proven metastatic breast cancer are alive and disease-free more than 10 years following cytotoxic systemic therapy alone. This realization that a long-term disease-free interval and potential cure was possible in breast cancer and other diseases led to the idea that not all patients with metastatic disease have the same clinical course. Mounting data suggests that patients with few (usually <5) radiographically visible tumors have the potential to be cured through local ablative therapy of visible metastases, often in combination with systemic therapy.

Authors
Chmura, SJ; Salama, JK
MLA Citation
Chmura, S. J., and J. K. Salama. “Stereotactic treatment for oligometastatic breast cancer.” Short Course Breast Radiotherapy: A Comprehensive Review of Hypofractionation, Partial Breast, and Intra-Operative Irradiation, 2015, pp. 467–81. Scopus, doi:10.1007/978-3-319-24388-7_29.
Source
scopus
Publish Date
2015
Start Page
467
End Page
481
DOI
10.1007/978-3-319-24388-7_29

Statin use is associated with decreased prostate cancer recurrence in men treated with brachytherapy.

PURPOSE/OBJECTIVE(S): Recent in vitro and in vivo evidence has suggested that statin medications may have anticancer activity. We sought to determine whether statin use was associated with improved clinical outcome in men treated with brachytherapy for prostate cancer. MATERIALS/METHODS: A database of men with prostate cancer treated with permanent Iodine-125 brachytherapy between January 1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e., American Brachytherapy Society selection criteria) were used for selecting patients for brachytherapy. Biochemical failure was defined using the Phoenix definition. RESULTS: From a total of 247 men with prostate adenocarcinoma treated with brachytherapy, 174 patients (70 %) were identified as using statin medications, either during initial visit or during follow-up. Median PSA follow-up was 51 months after date of implant (range 9.4-140.35). Overall biochemical failure rate was 7.3 % (18 patients). On univariate analysis, statin use was associated with significantly improved freedom from biochemical failure [hazard ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate Cox analysis performed with the variables statin use, pretreatment PSA, clinical T stage, Gleason score, and D90 or V100, statin use remained significantly associated with improved freedom from biochemical failure (HR 0.288; 95 % CI 0.086-0.886; p = 0.0299). CONCLUSIONS: Statin use was associated with a significant improvement in freedom from biochemical failure in this cohort of men treated with brachytherapy for prostate cancer. Further investigation into the favorable effect of statin use on brachytherapy and radiation therapy in general is warranted, including prospective trials.

Authors
Oh, DS; Koontz, B; Freedland, SJ; Gerber, L; Patel, P; Lewis, S; Yoo, DS; Oleson, J; Salama, JK
MLA Citation
Oh, Daniel S., et al. “Statin use is associated with decreased prostate cancer recurrence in men treated with brachytherapy..” World J Urol, vol. 33, no. 1, Jan. 2015, pp. 93–97. Pubmed, doi:10.1007/s00345-014-1281-x.
PMID
24671610
Source
pubmed
Published In
World J Urol
Volume
33
Issue
1
Publish Date
2015
Start Page
93
End Page
97
DOI
10.1007/s00345-014-1281-x

Surgery or ablative radiotherapy for breast cancer oligometastases.

Precisely focused radiation or surgical resection of limited metastases resulted in long-term disease control and survival in multiple studies of patients with oligometastatic breast cancer. The integration of these ablative techniques into standard systemic therapy regimens has the potential to be paradigm shifting, leaving many patients without evidence of disease. Although an attractive treatment option, the utility of these therapies have not been proven in controlled studies, and improved outcomes may be because of patient selection or favorable biology alone. Ongoing studies continue to refine radiation techniques and determine the role for ablative therapies in the management of patients with metastatic breast cancer (MBC). Additionally, patient selection for metastasis-directed therapies is based on clinical criteria, with many not benefiting from therapies that may have substantial toxicities. Recent reports are beginning to uncover the biology of oligometastatic cancer, but much work is needed. Current and developing trials that integrate both clinical and translational endpoints have the potential to transform management strategies in women with limited MBC.

Authors
Salama, JK; Chmura, SJ
MLA Citation
Salama, Joseph K., and Steven J. Chmura. “Surgery or ablative radiotherapy for breast cancer oligometastases..” Am Soc Clin Oncol Educ Book, 2015, pp. e8-15. Pubmed, doi:10.14694/EdBook_AM.2015.35.e8.
PMID
25993242
Source
pubmed
Published In
Am Soc Clin Oncol Educ Book
Publish Date
2015
Start Page
e8
End Page
15
DOI
10.14694/EdBook_AM.2015.35.e8

The evolving role of radiotherapy in treatment of oligometastatic NSCLC.

Non-small cell lung cancer (NSCLC) patients with metastases limited in site and number, termed oligometastases, may represent a unique subpopulation of advanced NSCLC with improved prognosis. The optimal management of these patients remains unclear with the treatment approach currently undergoing a paradigm shift. The potential benefit of aggressive metastasis directed local treatment with surgery and/or radiotherapy (RT) in combination with systemic therapy is bolstered predominantly by retrospective analyses but also by a growing number of non-randomized prospective studies regarding the use of ablative RT techniques including stereotactic body radiotherapy (SBRT), alternatively termed stereotactic ablative radiotherapy (SABR), directed at the primary tumor (if present) and all metastatic sites. Long-term survival is possible in a subset of patients treated aggressively in this manner. The challenge for the clinical oncology community moving forward is appropriately selecting patients for this treatment approach based on clinical, imaging, and molecular features and increasing enrollment of patients to prospective clinical trials to more definitively determine the added benefit and appropriate timing of aggressive metastasis directed therapy in the oligometastatic setting.

Authors
Bergsma, DP; Salama, JK; Singh, DP; Chmura, SJ; Milano, MT
MLA Citation
Bergsma, Derek P., et al. “The evolving role of radiotherapy in treatment of oligometastatic NSCLC..” Expert Rev Anticancer Ther, vol. 15, no. 12, 2015, pp. 1459–71. Pubmed, doi:10.1586/14737140.2015.1105745.
PMID
26536370
Source
pubmed
Published In
Expert Rev Anticancer Ther
Volume
15
Issue
12
Publish Date
2015
Start Page
1459
End Page
1471
DOI
10.1586/14737140.2015.1105745

The role of surgery and ablative radiotherapy in oligometastatic breast cancer.

The ability to deliver precise focused radiation, combined with improved surgical techniques, has led to multiple reports of long-term survivors in patients with oligometastatic breast cancer. The removal or ablation of known metastases, often present after systemic therapy regimens has the potential to be paradigm shifting rendering many patients without evidence of disease. However, the utility of these therapies has not been proven in phase III studies. Additionally, patient selection for metastasis-directed therapies is based on clinical criteria, with many patients not benefiting from these therapies. Refinements of radiation techniques are continuing, and discoveries are uncovering the biology of breast cancer in the oligometastatic state among patients. Integrated into ongoing studies, and those in development, they have the potential to alter standard management strategies in oligometastatic patients.

Authors
Salama, JK; Chmura, SJ
MLA Citation
Salama, Joseph K., and Steven J. Chmura. “The role of surgery and ablative radiotherapy in oligometastatic breast cancer..” Semin Oncol, vol. 41, no. 6, Dec. 2014, pp. 790–97. Pubmed, doi:10.1053/j.seminoncol.2014.09.016.
PMID
25499637
Source
pubmed
Published In
Semin Oncol
Volume
41
Issue
6
Publish Date
2014
Start Page
790
End Page
797
DOI
10.1053/j.seminoncol.2014.09.016

Is proton beam therapy better than standard radiation therapy? A paucity of practicality puts photons ahead of protons.

Authors
Salama, JK; Willett, CG
MLA Citation
Salama, Joseph K., and Christopher G. Willett. “Is proton beam therapy better than standard radiation therapy? A paucity of practicality puts photons ahead of protons..” Clin Adv Hematol Oncol, vol. 12, no. 12, Dec. 2014, pp. 861–69.
PMID
25674847
Source
pubmed
Published In
Clinical Advances in Hematology & Oncology : H&O
Volume
12
Issue
12
Publish Date
2014
Start Page
861
End Page
869

Racial differences in adipose tissue distribution and risk of aggressive prostate cancer among men undergoing radiotherapy.

BACKGROUND: Although elevated body mass index (BMI) has been associated with increased risk of aggressive prostate cancer, the importance of adipose tissue distribution is not well understood. We examined associations between overall and visceral obesity and aggressive prostate cancer risk. Moreover, given racial differences in adipose tissue distribution, we examined whether race modified these associations. METHODS: We conducted a cross-sectional analysis of 308 radiotherapy-treated patients with prostate cancer within the Durham VA from 2005 to 2011. Multivariable logistic regression examined the association between BMI categories and tertiles of waist circumference (WC), visceral fat area (VFA), and periprostatic adipose tissue area (PPAT) with high-grade prostate cancer risk (Gleason score ≥7 vs. ≤6). Models stratified by race examined whether these associations differed between black and nonblack men. RESULTS: Both elevated BMI (Ptrend = 0.054) and WC (Ptrend = 0.040) were associated with increased high-grade prostate cancer risk, with similar results between races, although the association with BMI was not statistically significant. In contrast, elevated VFA was associated with increased aggressive prostate cancer risk in black men (Ptrend = 0.002) but not nonblack men (Ptrend = 0.831), with a significant interaction between race and VFA (Pinteraction = 0.035). Though similar patterns were observed for PPAT, none was statistically significant. CONCLUSIONS: Among men undergoing radiotherapy for prostate cancer, visceral obesity is associated with increased aggressive prostate cancer risk, particularly among black men. If confirmed in future studies, these results suggest that adipose tissue distribution differences may contribute to prostate cancer racial disparity. IMPACT: These findings highlight the need to elucidate mechanisms contributing to racial differences in the association between visceral obesity and aggressive prostate cancer.

Authors
Allott, EH; Howard, LE; Song, H-J; Sourbeer, KN; Koontz, BF; Salama, JK; Freedland, SJ
MLA Citation
Allott, Emma H., et al. “Racial differences in adipose tissue distribution and risk of aggressive prostate cancer among men undergoing radiotherapy..” Cancer Epidemiol Biomarkers Prev, vol. 23, no. 11, Nov. 2014, pp. 2404–12. Pubmed, doi:10.1158/1055-9965.EPI-14-0236.
PMID
25146088
Source
pubmed
Published In
Cancer Epidemiol Biomarkers Prev
Volume
23
Issue
11
Publish Date
2014
Start Page
2404
End Page
2412
DOI
10.1158/1055-9965.EPI-14-0236

When is a biopsy-proven diagnosis necessary before stereotactic ablative radiotherapy for lung cancer?: A decision analysis.

BACKGROUND: The practice of treating a solitary pulmonary nodule (SPN) suspicious for stage I non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR) in the absence of pathology is growing. In the absence of randomized evidence, the appropriate prior probability threshold of lung cancer of when such a strategy is warranted can be informed using decision analysis. METHODS: A decision tree and Markov model were constructed to evaluate the relative merits of surveillance, a PET scan-directed SABR strategy (without pathology), or a PET scan-biopsy-SABR strategy, when faced with an SPN at different prior probabilities for lung cancer. Diagnostic characteristics, as well as disease, treatment, and toxicity parameters, were extracted from the literature. Deterministic analysis and probabilistic sensitivity analyses were performed to inform the appropriate lung cancer prior probability threshold between treatment strategies. RESULTS: In the reference case analysis, the prior probability threshold between surveillance and PET scan-biopsy-SABR was 17.0%; between PET scan-directed SABR and PET scan-biopsy-SABR, the threshold was 85.0%. The latter finding was confirmed on probabilistic sensitivity analysis (85.2%; 95% CI, 80.0% to 87.2%). This predicted lung cancer prior probability threshold was most sensitive to the diagnostic sensitivity of transthoracic biopsy (range, 77.2% to 94.0%) and the detection rate of false negatives on CT scan surveillance (range, 82.4% to 92.3%). CONCLUSIONS: This model suggests that if there are concerns about morbidity related to biopsy for an SPN, a PET scan-directed SABR strategy is warranted when the prior probability of lung cancer exceeds a point estimate of 85%.

Authors
Louie, AV; Senan, S; Patel, P; Ferket, BS; Lagerwaard, FJ; Rodrigues, GB; Salama, JK; Kelsey, C; Palma, DA; Hunink, MG
MLA Citation
Louie, Alexander V., et al. “When is a biopsy-proven diagnosis necessary before stereotactic ablative radiotherapy for lung cancer?: A decision analysis..” Chest, vol. 146, no. 4, Oct. 2014, pp. 1021–28. Pubmed, doi:10.1378/chest.13-2924.
PMID
24853550
Source
pubmed
Published In
Chest
Volume
146
Issue
4
Publish Date
2014
Start Page
1021
End Page
1028
DOI
10.1378/chest.13-2924

Radical irradiation of extracranial oligometastases.

Advances in radiotherapy planning and delivery have been used to treat patients with limited metastatic disease. With these techniques, high rates of treated metastasis control and low toxicity have been reported. Some patients have long disease-free intervals after radiotherapy similar to those seen after surgical resection. Ongoing studies will determine the benefit of these irradiation techniques to treat limited metastases, identify appropriate candidates, and assist in integrating these treatments into management strategies for specific diseases.

Authors
Salama, JK; Milano, MT
MLA Citation
Salama, Joseph K., and Michael T. Milano. “Radical irradiation of extracranial oligometastases..” J Clin Oncol, vol. 32, no. 26, Sept. 2014, pp. 2902–12. Pubmed, doi:10.1200/JCO.2014.55.9567.
PMID
25113765
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
32
Issue
26
Publish Date
2014
Start Page
2902
End Page
2912
DOI
10.1200/JCO.2014.55.9567

The oligometastatic state - separating truth from wishful thinking.

The oligometastatic paradigm implies that patients who develop a small number of metastatic lesions might achieve long-term survival if all these lesions are ablated with surgery or stereotactic radiotherapy. Clinical data indicate that the number of patients with oligometastatic disease receiving aggressive treatment is increasing rapidly. We examine the key evidence supporting or refuting the existence of an oligometastatic state. Numerous single-arm studies suggest that long-term survival is 'better-than-expected' after ablative treatment. However, the few studies with adequate controls raise the possibility that this long-term survival might not be due to the treatments themselves, but rather to the selection of patients based on favourable inclusion criteria. Furthermore, ablative treatments carry a risk of harming healthy tissue, yet the risk-benefit ratio cannot be quantified if the benefits are unmeasured. If the strategy of treating oligometastases is to gain widespread acceptance as routine clinical practice, there should be stronger evidence supporting its efficacy.

Authors
Palma, DA; Salama, JK; Lo, SS; Senan, S; Treasure, T; Govindan, R; Weichselbaum, R
MLA Citation
Palma, David A., et al. “The oligometastatic state - separating truth from wishful thinking..” Nat Rev Clin Oncol, vol. 11, no. 9, Sept. 2014, pp. 549–57. Pubmed, doi:10.1038/nrclinonc.2014.96.
PMID
24958182
Source
pubmed
Published In
Nature Reviews. Clinical Oncology
Volume
11
Issue
9
Publish Date
2014
Start Page
549
End Page
557
DOI
10.1038/nrclinonc.2014.96

When is a Biopsy-Proven Diagnosis Necessary Before Stereotactic Ablative Radiation Therapy for Lung Cancer? A Decision Analysis

Authors
Louie, AV; Senan, S; Patel, PR; Ferket, B; Lagerwaard, FJ; Rodrigues, GB; Salama, JK; Kelsey, CR; Palma, DA; Hunink, M
MLA Citation
Louie, A. V., et al. “When is a Biopsy-Proven Diagnosis Necessary Before Stereotactic Ablative Radiation Therapy for Lung Cancer? A Decision Analysis.” International Journal of Radiation Oncology*Biology*Physics, vol. 90, no. 1, Elsevier BV, 2014, pp. S138–39. Crossref, doi:10.1016/j.ijrobp.2014.05.597.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
90
Issue
1
Publish Date
2014
Start Page
S138
End Page
S139
DOI
10.1016/j.ijrobp.2014.05.597

A Multi-institution Pooled Analysis of Oligometastatic Patients Treated With SBRT

Authors
Lee, J; Milano, MT; Kao, J; Chmura, S; Salama, JK
MLA Citation
Lee, J., et al. “A Multi-institution Pooled Analysis of Oligometastatic Patients Treated With SBRT.” International Journal of Radiation Oncology*Biology*Physics, vol. 90, no. 1, Elsevier BV, 2014, pp. S699–S699. Crossref, doi:10.1016/j.ijrobp.2014.05.2050.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
90
Issue
1
Publish Date
2014
Start Page
S699
End Page
S699
DOI
10.1016/j.ijrobp.2014.05.2050

ACR Appropriateness Criteria® thyroid carcinoma.

The ACR Head and Neck Cancer Appropriateness Criteria Committee reviewed relevant medical literature to provide guidance for those managing patients with thyroid carcinoma. The American College of Radiology Appropriateness Criteriaare evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Thyroid cancer is the most common endocrine malignancy in the United States, most often presenting as a localized palpable nodule. Surgery is the mainstay of treatment for WDTC, with most patients undergoing complete resection of their disease having good outcomes. Following surgery thyroxine supplementation should begin to suppress TSH, which unchecked can stimulate residual disease and/or metastatic progression, Adjuvant treatment with radioactive iodine (RAI) using iodine-131 ((131)I) is frequently used for diagnostic and therapeutic purposes. The use of EBRT for thyroid cancer has not been tested in well-designed, randomized, controlled trials and should, therefore, be considered on a case-by-case basis. Chemotherapy plays a minimal role in the management of WDTC. Novel biologic agents, such as systemic therapy options, are being actively investigated, and patients with metastatic thyroid cancer that is not iodine avid should be encouraged to enroll in clinical trials exploring novel systemic agents.

Authors
Salama, JK; Golden, DW; Yom, SS; Garg, MK; Lawson, J; McDonald, MW; Quon, H; Ridge, JA; Saba, N; Smith, RV; Worden, F; Yeung, AR; Beitler, JJ
MLA Citation
Salama, Joseph K., et al. “ACR Appropriateness Criteria® thyroid carcinoma..” Oral Oncol, vol. 50, no. 6, June 2014, pp. 577–86. Pubmed, doi:10.1016/j.oraloncology.2013.12.004.
PMID
24824115
Source
pubmed
Published In
Oral Oncol
Volume
50
Issue
6
Publish Date
2014
Start Page
577
End Page
586
DOI
10.1016/j.oraloncology.2013.12.004

When is a pathologic diagnosis preferred before stereotactic ablative radiotherapy for stage I lung cancer? A decision analysis.

Authors
Louie, AV; Senan, S; Patel, P; Ferket, BS; Lagerwaard, FJ; Rodrigues, G; Salama, JK; Kelsey, CR; Palma, D; Hunink, M
MLA Citation
Louie, Alexander V., et al. “When is a pathologic diagnosis preferred before stereotactic ablative radiotherapy for stage I lung cancer? A decision analysis..” Journal of Clinical Oncology, vol. 32, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2014, pp. 7534–7534. Crossref, doi:10.1200/jco.2014.32.15_suppl.7534.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
32
Issue
15_suppl
Publish Date
2014
Start Page
7534
End Page
7534
DOI
10.1200/jco.2014.32.15_suppl.7534

Stereotactic body radiotherapy: a critical review for nonradiation oncologists.

Stereotactic body radiotherapy (SBRT) involves the treatment of extracranial primary tumors or metastases with a few, high doses of ionizing radiation. In SBRT, tumor kill is maximized and dose to surrounding tissue is minimized, by precise and accurate delivery of multiple radiation beams to the target. This is particularly challenging, because extracranial lesions often move with respiration and are irregular in shape, requiring careful treatment planning and continual management of this motion and patient position during irradiation. This review presents the rationale, process workflow, and technology for the safe and effective administration of SBRT, as well as the indications, outcome, and limitations for this technique in the treatment of lung cancer, liver cancer, and metastatic disease.

Authors
Kirkpatrick, JP; Kelsey, CR; Palta, M; Cabrera, AR; Salama, JK; Patel, P; Perez, BA; Lee, J; Yin, F-F
MLA Citation
Kirkpatrick, John P., et al. “Stereotactic body radiotherapy: a critical review for nonradiation oncologists..” Cancer, vol. 120, no. 7, Apr. 2014, pp. 942–54. Pubmed, doi:10.1002/cncr.28515.
PMID
24382744
Source
pubmed
Published In
Cancer
Volume
120
Issue
7
Publish Date
2014
Start Page
942
End Page
954
DOI
10.1002/cncr.28515

WHEN IS A PATHOLOGICAL DIAGNOSIS PREFERRED BEFORE STEREOTACTIC ABLATIVE RADIOTHERAPY (SABR) FOR STAGE I LUNG CANCER? A DECISION ANALYSIS

Authors
Louie, AV; Hunink, MG; Patel, P; Ferket, BS; Lagerwaard, FJ; Rodrigues, GB; Salama, JK; Kelsey, C; Palma, DA; Senan, S
MLA Citation
Louie, A. V., et al. “WHEN IS A PATHOLOGICAL DIAGNOSIS PREFERRED BEFORE STEREOTACTIC ABLATIVE RADIOTHERAPY (SABR) FOR STAGE I LUNG CANCER? A DECISION ANALYSIS.” Journal of Thoracic Oncology, vol. 9, no. 4, LIPPINCOTT WILLIAMS & WILKINS, Apr. 2014, pp. S31–S31.
Source
wos
Published In
Journal of Thoracic Oncology
Volume
9
Issue
4
Publish Date
2014
Start Page
S31
End Page
S31

Palliative radiotherapy for prostate cancer.

Radiotherapy is an effective tool for the palliation of symptoms commonly caused by prostate cancer. The majority of painful bone metastases respond equally well to single or multiple fractions of external radiotherapy. Retreatment with a second course of radiation induces pain responses in approximately 50% of patients. For more diffuse metastases, either hemibody radiation or systemic radiopharmaceuticals can reduce pain, and radium-223 is associated with improved survival in men with castration-resistant prostate cancer. Hematuria, bladder outlet obstruction, and rectal compression are all improved with palliative radiotherapy. The ability of stereotactic body radiation therapy to reduce pain compared with standard external radiation is being investigated, as is its role in treating those with limited metastatic disease.

Authors
Boyer, MJ; Salama, JK; Lee, WR
MLA Citation
Boyer, Matthew J., et al. “Palliative radiotherapy for prostate cancer..” Oncology (Williston Park), vol. 28, no. 4, Apr. 2014, pp. 306–12.
PMID
24839802
Source
pubmed
Published In
Oncology (Williston Park, N.Y.)
Volume
28
Issue
4
Publish Date
2014
Start Page
306
End Page
312

Palliative radiotherapy for prostate cancer.

Radiotherapy is an effective tool for the palliation of symptoms commonly caused by prostate cancer. The majority of painful bone metastases respond equally well to single or multiple fractions of external radiotherapy. Retreatment with a second course of radiation induces pain responses in approximately 50% of patients. For more diffuse metastases, either hemibody radiation or systemic radiopharmaceuticals can reduce pain, and radium-223 is associated with improved survival in men with castration-resistant prostate cancer. Hematuria, bladder outlet obstruction, and rectal compression are all improved with palliative radiotherapy. The ability of stereotactic body radiation therapy to reduce pain compared with standard external radiation is being investigated, as is its role in treating those with limited metastatic disease.

Authors
Boyer, MJ; Salama, JK; Lee, WR
MLA Citation
Boyer, M. J., et al. “Palliative radiotherapy for prostate cancer..” Oncology (Williston Park, N.Y.), vol. 28, no. 4, Jan. 2014, pp. 306–12.
Source
scopus
Published In
Oncology (Williston Park, N.Y.)
Volume
28
Issue
4
Publish Date
2014
Start Page
306
End Page
312

A paucity of practicality puts photons ahead of protons

Authors
Salama, JK; G.willett, C
MLA Citation
Salama, J. K., and C. G.willett. “A paucity of practicality puts photons ahead of protons.” Clinical Advances in Hematology and Oncology, vol. 12, no. 12, Jan. 2014, pp. 861–69.
Source
scopus
Published In
Clinical Advances in Hematology & Oncology : H&O
Volume
12
Issue
12
Publish Date
2014
Start Page
861
End Page
869

American College of Radiology Appropriateness Criteria(®) treatment of stage I T1 glottic cancer.

BACKGROUND: Controversy surrounds the appropriate therapy for T1 glottic cancer. Both transoral endolaryngeal resection and radiation offer excellent local control and voice quality; some lesions are best addressed with resection and others with radiation. METHODS: The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guideline development includes an analysis of current literature from peer reviewed journals and the well-established "modified Delphi" consensus methodology to rate the appropriateness of treatment. Where evidence is not definitive, expert opinion informed recommendations. RESULTS: The ACR Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for treatment of T1 glottic cancer. Treatment planning is complex and decisions nuanced. CONCLUSION: Best treatment for a particular cancer cannot be defined without consideration of the lesion's location, extent, depth of invasion, and quality of surgical exposure during direct laryngoscopy.

Authors
Ridge, JA; Lawson, J; Yom, SS; Garg, MK; McDonald, MW; Quon, H; Saba, N; Salama, JK; Smith, RV; Worden, F; Yeung, AR; Beitler, JJ
MLA Citation
Ridge, John A., et al. “American College of Radiology Appropriateness Criteria(®) treatment of stage I T1 glottic cancer..” Head Neck, vol. 36, no. 1, Jan. 2014, pp. 3–8. Pubmed, doi:10.1002/hed.23381.
PMID
23696520
Source
pubmed
Published In
Head Neck
Volume
36
Issue
1
Publish Date
2014
Start Page
3
End Page
8
DOI
10.1002/hed.23381

Stereotactic ablative body radiotherapy (SABR) for effective palliation of metastases: factors affecting local control.

We analyzed factors associated with inferior local control following stereotactic ablative body radiotherapy (SABR) for palliation of metastases. We reviewed records of patients receiving SABR for metastases at Duke University from 2006-2010. Biologically effective dose (BED) was calculated using the linear-quadratic model. Toxicity was assessed by CTCAE v4.0. The Kaplan-Meier method was used to estimate overall survival (OS) and local control (LC) within subgroups (primary or salvage SABR). Univariate (UVA) and multivariate (MVA) regression analysis was used. Fifty and 33 patients received primary and salvage SABR, respectively. 105 lesions were treated (52 spine, 27 lung, 7 liver, 11 other); 67 primary SABR and 38 salvage. Median clinical follow-up was 11.1 months and 10.3 months with imaging of the treated lesion. One patient received SABR x3 and died from toxicity. 88% of symptomatic patients improved after SABR. 1-year LC and OS were 83% and 50%, respectively. Primary SABR had higher BED and was associated with improved LC on UVA (HR 3.0, p=0.01) and MVA (p=0.02); treatment site and histology were not. SABR results in effective palliation of metastases regardless of prior treatment. In the absence of prior EBRT, SABR can be delivered with higher BED and may be associated with better outcomes.

Authors
Patel, PR; Kirkpatrick, J; Salama, JK; Nelson, J; Broadwater, G; Allen, K; Clough, R; Yin, F-F; Wang, Z; Chang, Z; Kelsey, C; Ghafoori, AP
MLA Citation
Patel, Pretesh R., et al. “Stereotactic ablative body radiotherapy (SABR) for effective palliation of metastases: factors affecting local control..” J Radiosurg Sbrt, vol. 3, no. 2, 2014, pp. 123–29.
PMID
29296393
Source
pubmed
Published In
Journal of Radiosurgery and Sbrt
Volume
3
Issue
2
Publish Date
2014
Start Page
123
End Page
129

Stereotactic body radiotherapy for the treatment of oligometastatic renal cell carcinoma.

OBJECTIVES: Renal cell carcinoma (RCC) is considered radioresistant, but stereotactic radiosurgery can control intracranial metastases. Advances in radiotherapy, such as stereotactic body radiotherapy (SBRT), allow high-dose radiation delivery to extracranial sites. Herein, we report our experience treating oligometastatic RCC with SBRT. METHODS: Patients with RCC and limited metastases were treated on a 3-fraction dose-escalation protocol (8 to 14 Gy/fraction) or off protocol with 10 fractions (4 to 5 Gy/fraction). Disease control was evaluated with serial imaging, and the Kaplan-Meier method was used to estimate lesion control (LeC), distant control, and survival. RESULTS: Eighteen consecutively treated patients with 39 metastases were treated using SBRT; 12 underwent treatment for all metastatic sites. Median follow-up was 16.2 months. Treatment was well tolerated; the most common acute toxicity was fatigue (61.1%) and late toxicity was limited. At 2 years, LeC was 91.4% and overall survival was 85%. Those who underwent treatment for all metastatic sites had a 2-year LeC of 100% and distant control of 35.7%. A shorter interval from diagnosis to SBRT predicted for distant progression. Freedom from any post-SBRT therapy was 64.2% at 1 year. CONCLUSIONS: In metastatic RCC, SBRT produces promising LeC with minimal toxicity. Further study should be expanded beyond that of managing intracranial disease. Its selected use may delay the requirement for systemic therapies.

Authors
Ranck, MC; Golden, DW; Corbin, KS; Hasselle, MD; Liauw, SL; Stadler, WM; Hahn, OM; Weichselbaum, RR; Salama, JK
MLA Citation
Ranck, Mark C., et al. “Stereotactic body radiotherapy for the treatment of oligometastatic renal cell carcinoma..” Am J Clin Oncol, vol. 36, no. 6, Dec. 2013, pp. 589–95. Pubmed, doi:10.1097/COC.0b013e31825d52b2.
PMID
22868242
Source
pubmed
Published In
American Journal of Clinical Oncology
Volume
36
Issue
6
Publish Date
2013
Start Page
589
End Page
595
DOI
10.1097/COC.0b013e31825d52b2

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

INTRODUCTION: Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70 Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. METHODS: Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70 Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. RESULTS: 100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p = 0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p = 0.05).). Furthermore,exposure of larger volumes of lung to lower (median V5 = 70%, p = 0.09, median V10 = 63%, p = 0.07), inter-mediate (median V20 = 50, p = 0.04) and high (median V60 = 25%, p = 0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose(median 31 Gy) p = 0.019. CONCLUSION: Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation.

Authors
Salama, JK; Pang, H; Bogart, JA; Blackstock, AW; Urbanic, JJ; Hogson, L; Crawford, J; Vokes, EE
MLA Citation
Salama, Joseph K., et al. “Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904..” Lung Cancer, vol. 82, no. 3, Dec. 2013, pp. 436–40.
PMID
24396884
Source
pubmed
Published In
Lung Cancer
Volume
82
Issue
3
Publish Date
2013
Start Page
436
End Page
440

Cell Cycle Progression (CCP) Score Significantly Predicts PSA Failure After EBRT

Authors
Salama, JK; Freedland, S; Gerber, L; Reid, J; Welbourn, W; Gutin, A; Sangale, Z; Brawer, M; Stone, S
MLA Citation
Salama, J. K., et al. “Cell Cycle Progression (CCP) Score Significantly Predicts PSA Failure After EBRT.” International Journal of Radiation Oncology*Biology*Physics, vol. 87, no. 2, Elsevier BV, 2013, pp. S125–S125. Crossref, doi:10.1016/j.ijrobp.2013.06.322.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
S125
End Page
S125
DOI
10.1016/j.ijrobp.2013.06.322

Feasibility and toxicity of hypofractionated image guided radiation therapy for large volume limited metastatic disease.

PURPOSE: Hypofractionated image guided radiation therapy (HIGRT) is increasingly used for limited metastases. Reported studies have mostly treated small volume tumors. Here, we report the toxicity and oncologic outcomes following treatment of large volume metastases. METHODS AND MATERIALS: HIGRT patients treated from October 2005 to March 2010 were reviewed. Gross tumor volumes (GTV) and planning target volumes (PTV) were obtained from planning software. A metastasis was considered large volume if the treated PTV exceeded 50 cc. Patients were treated with either 10-fraction (4-5 Gy per fraction) or 3-5 fraction (8-14 Gy per fraction) regimens. Toxicity was obtained from both prospectively collected databases and retrospectively from patient charts. RESULTS: Sixty-four patients with 93 treated lesions >50 cc were identified. The median GTV and PTV volumes were 41 and 119 cc, respectively. The median number of treated large volume lesions was 1, and a maximum of 3 large volume lesions were treated in a single patient. Primary malignancies included non-small cell lung cancer, renal cell, colorectal, breast, bladder, pituitary, small cell lung cancer, sarcoma, head-and-neck cancer, and hepatocellular cancer. Treated sites included lung (n = 33), regional lymph nodes (n = 20), bone (n = 17), adrenal (n = 9), and liver (n = 6). The most frequently used treatment regimen was 50 Gy in 5 Gy fractions. The median follow-up was 27 months for surviving patients. Treated lesion control was 78%. Low rates of acute and late grade 3 or higher toxicity were reported, with 3 and 5 patients experiencing each, respectively. CONCLUSIONS: HIGRT to large volume oligometastatic disease is tolerable and feasible with promising tumor control. Local radiation therapy should be considered in patients with large volume, limited metastatic disease.

Authors
Corbin, KS; Ranck, MC; Hasselle, MD; Golden, DW; Partouche, J; Wu, T; Chmura, SJ; Weichselbaum, RR; Salama, JK
MLA Citation
Corbin, Kimberly S., et al. “Feasibility and toxicity of hypofractionated image guided radiation therapy for large volume limited metastatic disease..” Pract Radiat Oncol, vol. 3, no. 4, Oct. 2013, pp. 316–22. Pubmed, doi:10.1016/j.prro.2012.08.006.
PMID
24674404
Source
pubmed
Published In
Pract Radiat Oncol
Volume
3
Issue
4
Publish Date
2013
Start Page
316
End Page
322
DOI
10.1016/j.prro.2012.08.006

Study of functional infrared imaging for early detection of mucositis in locally advanced head and neck cancer treated with chemoradiotherapy.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) has led to improved efficacy in treating locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) but has led to almost universal in-field mucositis. Patients treated with the same regimen often have differences in mucositis occurrence and severity. Mucositis induced via radiation is known to represent an intense inflammatory response histologically. We hypothesized that patients destined to display severe mucocutaneous toxicity would demonstrate greater alterations in thermal intensity early in therapy than identically treated counterparts. This will allow identification of patients that will require more intensive supportive care using thermal imaging technology. MATERIALS AND METHODS: Subjects with LA-SCCHN (oral cavity or oropharynx) being treated with the identical chemoradiotherapy regimen underwent baseline and weekly thermal imaging. Changes in skin temperature caused by mucositis and dermatitis compared with a reference area (ΔT were calculated and correlated to grade of mucositis based on NCI-CTCAE 3.0. RESULTS: Thirty-four subjects were enrolled. Grade 3 mucositis and dermatitis was observed in 53% and 21%, respectively. We observed a statistically significant positive association between an early rise in ΔT and mucositis grade (p value=0.03). CONCLUSIONS: Thermal imaging is able to detect small and early changes in skin surface temperature that may be associated with development of mucositis in patients being treated with chemoradiotherapy.

Authors
Cohen, EEW; Ahmed, O; Kocherginsky, M; Shustakova, G; Kistner-Griffin, E; Salama, JK; Yefremenko, V; Novosad, V
MLA Citation
Cohen, Ezra E. W., et al. “Study of functional infrared imaging for early detection of mucositis in locally advanced head and neck cancer treated with chemoradiotherapy..” Oral Oncol, vol. 49, no. 10, Oct. 2013, pp. 1025–31. Pubmed, doi:10.1016/j.oraloncology.2013.07.009.
PMID
23988569
Source
pubmed
Published In
Oral Oncol
Volume
49
Issue
10
Publish Date
2013
Start Page
1025
End Page
1031
DOI
10.1016/j.oraloncology.2013.07.009

Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy.

PURPOSE: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. METHODS AND MATERIALS: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. RESULTS: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. CONCLUSIONS: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.

Authors
Freedland, SJ; Gerber, L; Reid, J; Welbourn, W; Tikishvili, E; Park, J; Younus, A; Gutin, A; Sangale, Z; Lanchbury, JS; Salama, JK; Stone, S
MLA Citation
Freedland, Stephen J., et al. “Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy..” Int J Radiat Oncol Biol Phys, vol. 86, no. 5, Aug. 2013, pp. 848–53. Pubmed, doi:10.1016/j.ijrobp.2013.04.043.
PMID
23755923
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
86
Issue
5
Publish Date
2013
Start Page
848
End Page
853
DOI
10.1016/j.ijrobp.2013.04.043

A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

INTRODUCTION: Standard therapy for limited-stage small-cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy (RT) followed by prophylactic cranial radiotherapy. Although many consider the standard RT regimen to be 45 Gy in 1.5 Gy twice-daily fractions, this has failed to gain widespread acceptance. We pooled data of patients assigned to receive daily RT of 70 Gy from three, consecutive prospective Cancer and Leukemia Group B L-SCLC cancer trials and report the results here. METHODS: All patients from consecutive Cancer and Leukemia Group B L-SCLC trials (39808, 30002, and 30206) using high-dosage daily RT with concurrent chemotherapy were included, and analyzed for toxicity, disease control, and survival. Overall survival (OS) and progression-free survival (PFS) were modeled using Cox proportional hazards models. Prognostic variables for OS-rate and PFS-rate were assessed using logistic regression model. RESULTS: Two hundred patients were included. The median follow-up was 78 months. Grade 3 or greater esophagitis was 23%. The median OS for pooled population was 19.9 months (95% confidence interval [CI]: 16.7-22.3), and 5-year OS rate was 20% (95% CI: 16-27%). The 2-year PFS was 26% (95% CI: 21-32%). Multivariate analysis found younger age (p = 0.02; hazard ratio [HR]: 1.023; 95% CI: 21-32), and female sex (p = 0.02; HR:0.69; 95% CI: 0.50-0.94) independently associated with improved overall survival. CONCLUSION: Two-Gy daily RT to a total dosage of 70 Gy was well tolerated with similar survival to 45 Gy (1.5 Gy twice-daily). This experience may aid practitioners decide whether high-dosage daily RT with platinum-based chemotherapy is appropriate outside of a clinical trial.

Authors
Salama, JK; Hodgson, L; Pang, H; Urbanic, JJ; Blackstock, AW; Schild, SE; Crawford, J; Bogart, JA; Vokes, EE; Cancer and Leukemia Group B,
MLA Citation
Salama, Joseph K., et al. “A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904..” J Thorac Oncol, vol. 8, no. 8, Aug. 2013, pp. 1043–49. Pubmed, doi:10.1097/JTO.0b013e318293d8a4.
PMID
23715301
Source
pubmed
Published In
J Thorac Oncol
Volume
8
Issue
8
Publish Date
2013
Start Page
1043
End Page
1049
DOI
10.1097/JTO.0b013e318293d8a4

Stereotactic body radiation therapy for treatment of primary and metastatic pulmonary malignancies.

Stereotactic body radiation therapy (SBRT) has become the preferred treatment approach for patients with stage I non-small cell lung cancer who are medically inoperable or refuse surgery. SBRT consists of 3 to 5 radiation treatments delivered over a 10- to 14-day period. Local control is achieved in approximately 90% of patients, and the risk of toxicity is relatively low. Ongoing studies are examining whether SBRT can replace surgery for certain patients, the optimal dose-fractionation scheme, and how best to treat patients having central tumors near the primary tracheobronchial tree.

Authors
Kelsey, CR; Salama, JK
MLA Citation
Kelsey, Chris R., and Joseph K. Salama. “Stereotactic body radiation therapy for treatment of primary and metastatic pulmonary malignancies..” Surg Oncol Clin N Am, vol. 22, no. 3, July 2013, pp. 463–81. Pubmed, doi:10.1016/j.soc.2013.02.011.
PMID
23622074
Source
pubmed
Published In
Surg Oncol Clin N Am
Volume
22
Issue
3
Publish Date
2013
Start Page
463
End Page
481
DOI
10.1016/j.soc.2013.02.011

Stereotactic body radiotherapy in patients with stage I non-small-cell lung cancer aged 75 years and older: retrospective results from a multicenter consortium.

BACKGROUND: This study was a retrospective analysis of elderly patients treated with stereotactic body radiotherapy (SBRT) in the setting of a multi-institutional consortium. PATIENTS AND METHODS: Three institutions pooled data on patients aged ≥ 75 years who received SBRT for stage I non-small-cell lung cancer (NSCLC). Forty-seven tumors in 46 patients were analyzed in patients aged 75 to 92 years (median, 82 years). Treatment was delivered during 2007 to 2009, with a median follow-up of 12.4 months. All patients underwent staging positron emission tomography-computed tomography (PET-CT), and 87% of tumors were confirmed by biopsy results. Total doses were 35 to 60 Gy, mainly in 3 to 5 fractions. All tumors were treated using a linear accelerator, with 96% of patients receiving 3-dimensional (3D) conformal RT and 4% undergoing intensity modulated RT (IMRT). RESULTS: At the time of analysis, the local failure rate was 2% (1 of 47). The regional failure rate was 9% (4 of 47). The distant failure rate was 6% (3 of 47). The combined failure rate was 15% (7 of 47) because 1 patient experienced both regional and distant failure. Among 20 tumors with any acute toxicity, there were no ≥ grade 3 toxicities. Pneumonitis (n = 10) grades 1 (n = 3) and 2 (n = 2) was seen in 15% and 10% of patients, respectively; these data were missing for 25% of patients. CONCLUSION: SBRT in patients aged ≥ 75 years with stage I NSCLC proved tolerable, with toxicity rates comparable to those in younger patients. Excellent rates of local, regional, and distant control were achieved at a median follow-up of 12.4 months. This patient population represents a rapidly growing segment of the early lung cancer population, and SBRT appears to be a safe and effective treatment option for patients who are not optimal candidates for surgery.

Authors
Samuels, MA; Kandula, S; Koru-Sengul, T; Bogart, JA; Salama, JK; Aridgides, PD; Gajra, A; Lilenbaum, RC
MLA Citation
Samuels, Michael A., et al. “Stereotactic body radiotherapy in patients with stage I non-small-cell lung cancer aged 75 years and older: retrospective results from a multicenter consortium..” Clin Lung Cancer, vol. 14, no. 4, July 2013, pp. 446–51. Pubmed, doi:10.1016/j.cllc.2013.03.004.
PMID
23660522
Source
pubmed
Published In
Clin Lung Cancer
Volume
14
Issue
4
Publish Date
2013
Start Page
446
End Page
451
DOI
10.1016/j.cllc.2013.03.004

Stereotactic body radiation therapy for curative treatment of adrenal metastases.

The detection of oligometastatic adrenal metastases is increasing and there are limited data supporting the use of curative intent stereotactic body radiation therapy (SBRT) to treat patients with limited metastatic disease with adrenal involvement. Therefore, we utilized a prospectively maintained database of consecutive patients treated with SBRT for limited metastatic disease (≤5 sites) to identify patients with adrenal metastases. Patients were either treated on a three-fraction dose escalation protocol or a ten fraction off-protocol regimen. Outcomes including treated-metastasis control (TMC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method. Ten patients with 13 adrenal metastases were identified for this case series. The median follow-up was 14.9 months. No patient experienced grade 3 toxicity. The most common grade 1-2 acute toxicities were fatigue (80%) and GI toxicity (40%). One patient experienced late grade 2 adrenal insufficiency. Overall, the 1-year TMC rate was 73%, DC was 30%, and OS was 90%. Three treated adrenal metastases progressed, all receiving the lowest BED10 (43.2 Gy), corresponding to 24 Gy in 3 fractions. After treatment of adrenal metastases with SBRT, the median time to salvage chemotherapy was 5.3 months (range 1.0-38.8 months) and 1-year freedom from salvage chemotherapy was 44%. These results suggest that SBRT to adrenal metastases was tolerated with low toxicity in limited metastatic patients and control rates are promising. This study supports the growing body of literature treating patients with adrenal metastases with SBRT.

Authors
Rudra, S; Malik, R; Ranck, MC; Farrey, K; Golden, DW; Hasselle, MD; Weichselbaum, RR; Salama, JK
MLA Citation
Rudra, Sonali, et al. “Stereotactic body radiation therapy for curative treatment of adrenal metastases..” Technol Cancer Res Treat, vol. 12, no. 3, June 2013, pp. 217–24. Pubmed, doi:10.7785/tcrt.2012.500320.
PMID
23369155
Source
pubmed
Published In
Technology in Cancer Research & Treatment
Volume
12
Issue
3
Publish Date
2013
Start Page
217
End Page
224
DOI
10.7785/tcrt.2012.500320

New radiotherapy and chemoradiotherapy approaches for non-small-cell lung cancer.

Recent advances in systemic cytotoxic and molecularly targeted therapies coupled with technologic strides in radiotherapy have the potential to improve outcomes for patients with non-small-cell lung cancer (NSCLC). Investigations are ongoing to identify optimal cytotoxin-based chemoradiotherapy platforms. The influence of specific histologic and molecular mutation status on the combination of targeted therapies and radiotherapy is also being actively studied. Although there are no convincing randomized phase III data to date supporting a survival advantage for combining molecularly targeted agents with radiation or chemoradiotherapy in the setting of locally advanced NSCLC, phase II and III studies targeted to elderly patients and those with poor performance status are elucidating preferred chemoradiotherapy strategies. Radiotherapy dose escalation did not improve chemoradiotherapy outcomes, although increasing radiation dose-intensity with modern techniques is being actively studied. As modern radiotherapy techniques have been shown to improve outcomes of some patients with limited metastatic disease, investigations are ongoing regarding how to optimally integrate them with standard chemotherapy platforms.

Authors
Salama, JK; Vokes, EE
MLA Citation
Salama, Joseph K., and Everett E. Vokes. “New radiotherapy and chemoradiotherapy approaches for non-small-cell lung cancer..” J Clin Oncol, vol. 31, no. 8, Mar. 2013, pp. 1029–38. Pubmed, doi:10.1200/JCO.2012.44.5064.
PMID
23401449
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
31
Issue
8
Publish Date
2013
Start Page
1029
End Page
1038
DOI
10.1200/JCO.2012.44.5064

A phase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade™ Biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation.

BACKGROUND: AdGV.EGR.TNF.11D (TNFerade™ Biologic) is a replication-deficient adenoviral vector expressing human tumor necrosis factor alpha (TNF-α) under the control of the chemoradiation-inducible EGR-1 promoter. TNF-α has been shown to function as a radiation sensitizer. We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of TNFerade™ Biologic, when added to chemoradiotherapy in poor prognosis patients with recurrent, previously irradiated head and neck cancer (HNC). METHODS: TNFerade™ Biologic was injected intratumorally on day 1 of each 14-day cycle and dose-escalated in log increments from 4 × 10(9) to 4 × 10(11) PU. Daily radiation, infusional 5-fluorouracil (5-FU), and hydroxyurea were given on days 1-5 for seven cycles (FHX). Tumor biopsies were obtained before, during, and after treatment. RESULTS: Fourteen patients were treated. DLT was reached at a dose level of 3 (4 × 10(11) PU) with three thrombotic events. The response rate was 83.3%. The median survival was 9.6 months. One patient (7.1%) remained alive 3 years after treatment. Biopsies were obtained in 90% of patients. Nearly all tumors expressed adenovirus receptors, TNF-α, and TNF-α receptors. Adenoviral DNA was detected in three biopsies from one patient. CONCLUSIONS: TNFerade™ Biologic can be safely integrated with FHX chemoradiotherapy at an MTD of 4 × 10(10) PU. Monitoring for thrombotic events is indicated.

Authors
Seiwert, TY; Darga, T; Haraf, D; Blair, EA; Stenson, K; Cohen, EEW; Salama, JK; Villaflor, V; Witt, ME; Lingen, MW; Weichselbaum, RR; Vokes, EE
MLA Citation
Seiwert, T. Y., et al. “A phase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade™ Biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation..” Ann Oncol, vol. 24, no. 3, Mar. 2013, pp. 769–76. Pubmed, doi:10.1093/annonc/mds523.
PMID
23104721
Source
pubmed
Published In
Ann Oncol
Volume
24
Issue
3
Publish Date
2013
Start Page
769
End Page
776
DOI
10.1093/annonc/mds523

Reply, contralateral irradiation for T(limited)N2bM0 lateralized tonsil cancer.

Authors
Garg, MK; Ridge, JA; Yom, SS; McDonald, MW; Quon, H; Smith, RV; Yeung, AR; Lawson, J; Saba, N; Salama, JK; Beitler, JJ
MLA Citation
Garg, Madhur K., et al. “Reply, contralateral irradiation for T(limited)N2bM0 lateralized tonsil cancer..” Head Neck, vol. 35, no. 3, Mar. 2013, pp. 465–66. Pubmed, doi:10.1002/hed.23212.
PMID
23386559
Source
pubmed
Published In
Head Neck
Volume
35
Issue
3
Publish Date
2013
Start Page
465
End Page
466
DOI
10.1002/hed.23212

Prognostic utility of CCP score in men with prostate cancer after primary external beam radiation therapy

Authors
Freedland, SJ; Gerber, L; Reid, JE; Welbourn, W; Tikishvili, E; Park, J; Younus, A; Gutin, A; Sangale, Z; Lanchbury, JS; Salama, JK; Stone, S
MLA Citation
Freedland, Stephen J., et al. “Prognostic utility of CCP score in men with prostate cancer after primary external beam radiation therapy.” Journal of Clinical Oncology, vol. 31, no. 6, AMER SOC CLINICAL ONCOLOGY, 2013. Wos, doi:10.1200/jco.2013.31.6_suppl.47.
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
31
Issue
6
Publish Date
2013
DOI
10.1200/jco.2013.31.6_suppl.47

Prognostic utility of CCP score in men with prostate cancer after primary external beam radiation therapy.

47 Background: Accurate risk stratification improves decision making in localized prostate cancer. The CCP score, a prognostic RNA signature based on the average expression level of 31 cell cycle progression (CCP) genes, was developed to aid in this task. Previously, the CCP score was shown to be predictive of biochemical recurrence (BCR) after prostatectomy, and prostate cancer specific mortality in men undergoing observation. However, the value of CCP score in men undergoing primary electron beam radiation therapy (EBRT) was untested. METHODS: The CCP score was derived retrospectively from the diagnostic biopsy of 141 patients treated with EBRT at the Durham VA medical Center. Inclusion criteria were disease diagnosis from 1991 to 2006 and available biopsy tissue. Approximately half of the cohort was African-American. Outcome was time from EBRT to BCR using Phoenix definition, and median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by CoxPH survival analysis and likelihood ratio tests. RESULTS: Patient data were censored at 5-years of follow-up and 19 patients (13%) had BCR. The median CCP score was 0.12(IQR -0.43 to 0.66). In univariable analysis, CCP score was a significant prognostic variable (p-value = 0.0017). The hazard ratio (HR) for BCR was 2.55 (95% CI (1.43, 4.55)) for a one-unit increase in CCP score (equivalent to a doubling of gene expression). In a predefined multivariable analysis that included Gleason score, PSA, and percent positive cores, the HR for CCP changed only marginally and remained significant (HR per CCP unit 2.09 (95% CI (1.05, 4.18), p-value = 0.035), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. Further adjustment for hormonal therapy or radiation dose did not materially alter this association. The score was also associated with prostate cancer specific mortality. There was no evidence for interaction between CCP and any clinical variable, including ethnicity. CONCLUSIONS: In a cohort of men treated with EBRT, the CCP score was significantly associated with outcome and provided prognostic information beyond what was available from clinical parameters. If validated in a larger cohort, CCP score could be used to select high-risk men undergoing EBRT who may need combination therapy for their clinically localized prostate cancer.

Authors
Gerber, L; Reid, JE; Welbourn, W; Tikishvili, E; Park, J; Younus, A; Gutin, A; Sangale, Z; Lanchbury, JS; Salama, JK; Stone, S
MLA Citation
Gerber, L., et al. “Prognostic utility of CCP score in men with prostate cancer after primary external beam radiation therapy..” J Clin Oncol, vol. 31, no. 6_suppl, Feb. 2013. Pubmed, doi:10.1200/jco.2013.31.6_suppl.47.
PMID
28137032
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
31
Issue
6_suppl
Publish Date
2013
Start Page
47
DOI
10.1200/jco.2013.31.6_suppl.47

Oligometastases/oligo-recurrence of lung cancer

Authors
Niibe, Y; Chang, JY; Onishi, H; Salama, J; Hiraki, T; Yamashita, H
MLA Citation
Niibe, Y., et al. “Oligometastases/oligo-recurrence of lung cancer.” Pulmonary Medicine, Jan. 2013. Scopus, doi:10.1155/2013/438236.
Source
scopus
Published In
Pulmonary Medicine
Publish Date
2013
DOI
10.1155/2013/438236

Stereotactic radiotherapy for pulmonary metastases.

The most common treatment of pulmonary metastasis for solid tumors employs systemic chemotherapy, hormonal therapy, or biologic agents. Some series have suggested that aggressive surgical resection of pulmonary metastasis may improve patient outcomes in terms of quality of life and overall survival. Recently, data from clinical trials and retrospective series support the use of aggressive local control with high conformal dose radiotherapy (stereotactic body radiation therapy) in patients with limited metastases or oligometastases. Further evidence suggests that these patients represent a distinct clinical and biological class of patients. This review focuses on the role of ablative doses of radiotherapy in the treatment of pulmonary metastases. Specifically we discuss the rationale, treatment delivery, and local control that have led to the ongoing randomized clinical trials attempting to demonstrate a benefit over the current palliative standard of care.

Authors
Chmura, SJ; Salama, JK; Weichselbaum, RR
MLA Citation
Chmura, Steven J., et al. “Stereotactic radiotherapy for pulmonary metastases..” Semin Thorac Cardiovasc Surg, vol. 25, no. 4, 2013, pp. 292–99. Pubmed, doi:10.1053/j.semtcvs.2014.01.003.
PMID
24673958
Source
pubmed
Published In
Semin Thorac Cardiovasc Surg
Volume
25
Issue
4
Publish Date
2013
Start Page
292
End Page
299
DOI
10.1053/j.semtcvs.2014.01.003

The utility of FDG-PET for assessing outcomes in oligometastatic cancer patients treated with stereotactic body radiotherapy: a cohort study.

BACKGROUND: Studies suggest that patients with metastases limited in number and destination organ benefit from metastasis-directed therapy. Stereotactic body radiotherapy (SBRT) is commonly used for metastasis directed therapy in this group. However, the characterization of PET response following SBRT is unknown in this population. We analyzed our cohort of patients to describe the PET response following SBRT. METHODS: Patients enrolled on a prospective dose escalation trial of SBRT to all known sites of metastatic disease were reviewed to select patients with pre- and post-therapy PET scans. Response to SBRT was characterized on PET imaging based on standard PET response criteria and compared to CT based RECIST criteria for each treated lesion. RESULTS: 31 patients had PET and CT data available before and after treatment for analysis in this study. In total, 58 lesions were treated (19 lung, 11 osseous, 11 nodal, 9 liver, 6 adrenal and 2 soft tissue metastases). Median follow-up was 14 months (range: 3-41). Median time to first post-therapy PET was 1.2 months (range; 0.5-4.1). On initial post-therapy PET evaluation, 96% (56/58) of treated metastases responded to therapy. 60% (35/58) had a complete response (CR) on PET and 36% (21/58) had a partial response (PR). Of 22 patients with stable disease (SD) on initial CT scan, 13 had CR on PET, 8 had PR, and one had SD. Of 21 metastases with PET PR, 38% became CR, 52% remained PR, and 10% had progressive disease on follow-up PET. 10/35 lesions (29%) with an initial PET CR progressed on follow-up PET scan with median time to progression of 4.11 months (range: 2.75-9.56). Higher radiation dose correlated with long-term PET response. CONCLUSIONS: PET response to SBRT enables characterization of metastatic response in tumors non-measurable by CT. Increasing radiation dose is associated with prolonged complete response on PET.

Authors
Solanki, AA; Weichselbaum, RR; Appelbaum, D; Farrey, K; Yenice, KM; Chmura, SJ; Salama, JK
MLA Citation
Solanki, Abhishek A., et al. “The utility of FDG-PET for assessing outcomes in oligometastatic cancer patients treated with stereotactic body radiotherapy: a cohort study..” Radiat Oncol, vol. 7, Dec. 2012. Pubmed, doi:10.1186/1748-717X-7-216.
PMID
23244066
Source
pubmed
Published In
Radiation Oncology
Volume
7
Publish Date
2012
Start Page
216
DOI
10.1186/1748-717X-7-216

Stereotactic body radiotherapy treatment of extracranial metastases.

Radiotherapy is an integral treatment for patients with metastatic cancer, although it is usually reserved for palliation of pain, dyspnoea, oedema, bleeding and neurological symptoms. However, the administration of high-precision radiotherapy, termed stereotactic body radiotherapy (SBRT), has the potential to significantly affect the disease course for some patients with metastatic cancer by delivering high doses of radiation to the secondary tumours with limited high-dose delivery to adjacent healthy tissues. Indeed, such accurate delivery has been firmly established as a therapy for medically inoperable early-stage non-small-cell lung cancer. To date, the technique has demonstrated improvements in controlling metastasis and, in some cases, improved palliation compared with conventionally fractionated radiotherapy. Active areas of research in SBRT include patient selection for curative intent, optimization of SBRT planning techniques, dosing schema and integration of SBRT into systemic therapies. Given the improvements in cytotoxic and targeted therapies over the past decade, studies testing the careful integration of SBRT into standard systemic therapy regimens are needed. Further investigations are also needed to understand the basic biological mechanisms underlying SBRT because they are likely to be different to those mechanisms in conventional radiotherapy.

Authors
Salama, JK; Kirkpatrick, JP; Yin, F-F
MLA Citation
Salama, Joseph K., et al. “Stereotactic body radiotherapy treatment of extracranial metastases..” Nat Rev Clin Oncol, vol. 9, no. 11, Nov. 2012, pp. 654–65. Pubmed, doi:10.1038/nrclinonc.2012.166.
PMID
23007273
Source
pubmed
Published In
Nature Reviews. Clinical Oncology
Volume
9
Issue
11
Publish Date
2012
Start Page
654
End Page
665
DOI
10.1038/nrclinonc.2012.166

Performance and quality of life outcomes for T4 laryngeal cancer patients treated with induction chemotherapy followed by chemoradiotherapy.

Organ-sparing approaches with chemoradiotherapy are often used in the treatment of patients with laryngeal cancer, and the oncologic outcomes of these patients are similar to patients who undergo laryngectomy. However, chemoradiotherapy for laryngeal cancer patients with large or locally-invasive (T4) tumors has been more slowly incorporated due to concern for poor post-treatment function of the preserved larynx. Here, we characterize acute and long-term performance and quality-of-life (QOL) outcomes of T4 laryngeal cancer patients treated with induction chemotherapy followed by combined chemoradiotherapy. Using several validated metrics, we find patients experience a decline in most measures of performance and QOL during and immediately following treatment. However, the majority of patients improve to baseline over varying lengths of time following completion of treatment, and many go on to exceed pre-treatment levels of function. Gender, race, alcohol, and tobacco usage were found to be associated with differences in performance and QOL scores across time points. This study suggests that patients with advanced laryngeal tumors who historically had been considered poor candidates for organ-sparing treatment are able to return to, and in many cases exceed pre-treatment performance and QOL following induction chemotherapy and combined chemoradiotherapy.

Authors
Mouw, KW; Solanki, AA; Stenson, KM; Witt, ME; Blair, EA; Cohen, EEW; Vokes, EE; List, M; Haraf, DJ; Salama, JK
MLA Citation
Mouw, Kent W., et al. “Performance and quality of life outcomes for T4 laryngeal cancer patients treated with induction chemotherapy followed by chemoradiotherapy..” Oral Oncol, vol. 48, no. 10, Oct. 2012, pp. 1025–30. Pubmed, doi:10.1016/j.oraloncology.2012.04.004.
PMID
22621836
Source
pubmed
Published In
Oral Oncol
Volume
48
Issue
10
Publish Date
2012
Start Page
1025
End Page
1030
DOI
10.1016/j.oraloncology.2012.04.004

Reirradiation for recurrent head and neck cancer.

Recurrence of head and neck cancer in a previously irradiated volume presents a challenging problem and has poor prognosis. A minority of patients are eligible for the preferred therapy, surgical resection. Systemic therapy is offered to patients with unresectable disease but offers little, if any, chance of cure. Repeat irradiation with systemic therapy is a potentially curative option. One randomized trial and several cooperative group and institutional studies support its use. Long-term disease-free survival has been observed, albeit with the risk of significant, possibly life threatening, late complications. Intensity-modulated radiotherapy has been shown to reduce toxicity and improve disease control. Novel systemic therapies and radiotherapy techniques, including stereotactic body radiotherapy, are under active study.

Authors
Patel, PR; Salama, JK
MLA Citation
Patel, Pretesh R., and Joseph K. Salama. “Reirradiation for recurrent head and neck cancer..” Expert Rev Anticancer Ther, vol. 12, no. 9, Sept. 2012, pp. 1177–89. Pubmed, doi:10.1586/era.12.97.
PMID
23098118
Source
pubmed
Published In
Expert Rev Anticancer Ther
Volume
12
Issue
9
Publish Date
2012
Start Page
1177
End Page
1189
DOI
10.1586/era.12.97

Chemoradiation for patients with large-volume laryngeal cancers.

BACKGROUND: Patients with T4 laryngeal cancers, including those with large-volume (cartilage or tongue-base invasion) lesions, are often excluded from organ-preservation trials due to expectations of inferior outcome in terms of survival and function. We hypothesize that such patients indeed have acceptable survival and function when treated with organ-preservation strategies. METHODS: Retrospective analysis of prospectively collected data of a cohort of patients with T4 laryngeal cancer was carried out. Follow-up ranged from 0.18 to 15.6 years. All T4 laryngeal cancer patients who were enrolled in the University of Chicago concomitant chemoradiotherapy protocols from 1994 to the present were reviewed. This study was composed of 80 newly diagnosed T4 laryngeal cancer patients. Efficacy of treatment was determined through evaluations of survival and function. Survival was evaluated via Kaplan-Meier methods. Swallowing function was evaluated by an oropharyngeal motility (OPM) study and swallowing scores were assigned. Higher scores reflected increasing swallowing dysfunction. RESULTS: Fifty-five of 80 patients (~69%) had documented large-volume tumor. Two- and 5-year overall survivals were 60.0% and 48.7%, respectively. Disease-specific 2- and 5-year survivals for the group were 80.1% and 71.3%, and 79.4 and 74.3%, respectively, for the 55 patients with large volume status. Progression-free survival rates were 52.6% and 47.6%. Forty-four of 65 patients (~68%) with OPM data had a Swallowing Performance Status Scale (SPSS) score of ≤5, indicating various degrees of swallowing abnormalities not requiring a gastrostomy tube. This is a functional-preservation rate of 67.7%. CONCLUSIONS: Chemoradiation for patients with T4 laryngeal cancer appears to be an effective and reasonable option, particularly in light of the satisfactory survival and function-preservation rates.

Authors
Stenson, KM; Maccracken, E; Kunnavakkam, R; W Cohen, EE; Portugal, LD; Villaflor, V; Seiwert, T; Blair, E; Haraf, DJ; Salama, JK; Vokes, EE
MLA Citation
Stenson, Kerstin M., et al. “Chemoradiation for patients with large-volume laryngeal cancers..” Head Neck, vol. 34, no. 8, Aug. 2012, pp. 1162–67. Pubmed, doi:10.1002/hed.21888.
PMID
22052816
Source
pubmed
Published In
Head Neck
Volume
34
Issue
8
Publish Date
2012
Start Page
1162
End Page
1167
DOI
10.1002/hed.21888

Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease.

BACKGROUND: A subset of patients with metastatic cancer in limited organs may benefit from metastasis-directed therapy. The authors investigated whether patients with limited metastases could be safely treated with metastasis-directed radiotherapy. METHODS: Patients with 1 to 5 metastatic cancer sites with a life expectancy of >3 months received escalating stereotactic body radiotherapy (SBRT) doses to all known cancer sites. Patients were followed radiographically with CT scans of the chest, abdomen, and pelvis and metabolically with fluorodeoxyglucose-positron emission tomography, 1 month after treatment, and then every 3 months. Acute toxicities were scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0, and late toxicities were scored using the Radiation Therapy Oncology Group late toxicity scoring system. RESULTS: Sixty-one patients with 113 metastases were enrolled from November 2004 to November 2009 on a prospective radiation dose escalation study. Median follow-up was 20.9 months. Patients tolerated treatment well; the maximal tolerated dose was not reached in any cohort. Eleven patients (18.3%) have not progressed. One and 2-year progression-free survival are 33.3% (95% confidence interval [CI], 22.8-46.1) and 22.0% (95% CI, 12.8-34.4); 1-year and 2-year overall survival are 81.5% (95% CI, 71.1-91.1) and 56.7% (95% CI, 43.9-68.9). Seventy-two percent of patients whose tumors progressed did so in limited (1-3) metastatic sites. CONCLUSIONS: Patients with 1 to 5 metastases can be safely treated to multiple body sites and may benefit from SBRT. Further investigation should focus on patient selection.

Authors
Salama, JK; Hasselle, MD; Chmura, SJ; Malik, R; Mehta, N; Yenice, KM; Villaflor, VM; Stadler, WM; Hoffman, PC; Cohen, EEW; Connell, PP; Haraf, DJ; Vokes, EE; Hellman, S; Weichselbaum, RR
MLA Citation
Salama, Joseph K., et al. “Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease..” Cancer, vol. 118, no. 11, June 2012, pp. 2962–70. Pubmed, doi:10.1002/cncr.26611.
PMID
22020702
Source
pubmed
Published In
Cancer
Volume
118
Issue
11
Publish Date
2012
Start Page
2962
End Page
2970
DOI
10.1002/cncr.26611

SU-E-J-23: Prostate Bed Motion Study Using Surgical Clips Based on Daily CBCT.

PURPOSE: To study prostate-bed motion after prostatectomy using the surgical clips as a surrogate. METHODS: On the treatment planning CT, surgical clips within the PTV are identified and contoured. They are also identified and contoured in each daily CBCT. The center of mass (COM) coordinates for each clip within the native reference frame of each image set of CT and CBCT are recorded. Each CBCT (for daily image guidance) is registered to the planning CT based on the pelvic bony structure. The resulted 3D transformation matrix is used to convert the clip coordinates in the CBCT to the planning CT reference frame. Difference between the converted COM coordinates and the one in planning CT is taken as the rigid motion of the prostate bed relative to the pelvic bony structure during the course of radiation therapy. The motion data are then analyzed using statistical error analysis and quantified by the commonly defined M (average over all fractions and all patients), S (stdev of averages per patient, the systematic motion), and s (root mean square of stdev per patient, the random motion). Among a large pool of patients, seven patients were selected for this retrospective study, each with 3 to 11 identifiable clips and 17 to 26 CBCT sets. The total number of clips is 44 and total daily CBCT sets 160. RESULTS: In the (right-left, anterio-posterior, foot-head) directions, the M values are (0.2 mm, 0.4 mm, -0.6 mm), S (0.2, 2.5, 3.2), and s (1.7, 2.6, 2.1). CONCLUSIONS: Relative to the bony pelvic structure, the prostate bed motion characteristics are similar to that of intact prostate, as summarized in Table 2 of Rasch et al 2005 ('Target Definition in Prostate, Head, and Neck.' Semin Radiat Oncol 15:136-145).

Authors
Song, H; Salama, J; Yoo, D; Oleson, J; Wu, Q
MLA Citation
Song, H., et al. “SU-E-J-23: Prostate Bed Motion Study Using Surgical Clips Based on Daily CBCT..” Med Phys, vol. 39, no. 6Part6, June 2012. Pubmed, doi:10.1118/1.4734856.
PMID
28517607
Source
pubmed
Published In
Med Phys
Volume
39
Issue
6Part6
Publish Date
2012
Start Page
3657
DOI
10.1118/1.4734856

ACR Appropriateness Criteria® ipsilateral radiation for squamous cell carcinoma of the tonsil.

BACKGROUND: Controversy exists as to the criteria for selecting patients with carcinoma of the tonsil for treatment with ipsilateral radiotherapy (RT). METHODS: The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of treatment procedures by the panel. In those instances where evidence is not definitive, expert opinion may be used to recommend treatment. RESULTS: The ACR Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for selecting patients with tonsillar carcinoma for ipsilateral RT. CONCLUSION: Patients that are appropriate for ipsilateral RT have less than 1 cm of tumor invasion into the soft palate or base of tongue, and nodal stage of N0 to 1.

Authors
Expert Panel on Radiation Oncology--Head & Neck Cancer:, ; Yeung, AR; Garg, MK; Lawson, J; McDonald, MW; Quon, H; Ridge, JA; Saba, N; Salama, JK; Smith, RV; Yom, SS; Beitler, JJ; American College of Radiology,
MLA Citation
Expert Panel on Radiation Oncology--Head & Neck Cancer:, Jonathan J., et al. “ACR Appropriateness Criteria® ipsilateral radiation for squamous cell carcinoma of the tonsil..” Head Neck, vol. 34, no. 5, May 2012, pp. 613–16. Pubmed, doi:10.1002/hed.21993.
PMID
22250010
Source
pubmed
Published In
Head Neck
Volume
34
Issue
5
Publish Date
2012
Start Page
613
End Page
616
DOI
10.1002/hed.21993

Abstract 3405: MicroRNA expression characterizes oligometastasis(es)

Authors
Xing, RH; Lussier, YA; Salama, JK; Khodarev, NN; Huang, Y; Zhang, Q; Khan, SA; Yang, X; Hasselle, MD; Darga, TE; Malik, R; Fan, H; Perakis, S; Filippo, M; Corbin, K; Lee, Y; Posner, MC; Chmura, SJ; Hellman, S; Weichselbaum, RR
MLA Citation
Xing, Rosie Hongmei, et al. “Abstract 3405: MicroRNA expression characterizes oligometastasis(es).” Tumor Biology, American Association for Cancer Research, Apr. 2012. Crossref, doi:10.1158/1538-7445.am2012-3405.
Source
crossref
Published In
Tumor Biology
Publish Date
2012
DOI
10.1158/1538-7445.am2012-3405

Abstract 1369: Mouse models of clinical oligo- and poly-metastatic progression

Authors
Zhang, Q; Yang, X; Shen, J; Salama, JK; Khodarev, N; Hasselle, MD; Huang, Y; Fan, H; Khan, SA; Darga, TE; Hoffma, RM; Chmura, S; Lussier, YA; Weichselbaum, RR; Xing, RH
MLA Citation
Zhang, Qingbei, et al. “Abstract 1369: Mouse models of clinical oligo- and poly-metastatic progression.” Tumor Biology, American Association for Cancer Research, Apr. 2012. Crossref, doi:10.1158/1538-7445.am2012-1369.
Source
crossref
Published In
Tumor Biology
Publish Date
2012
DOI
10.1158/1538-7445.am2012-1369

American College of Radiology Appropriateness Criteria on retreatment of recurrent head-and-neck cancer after prior definitive radiation

Authors
McDonald, MW; Lawson, J; Yom, SS; Garg, MK; Quon, H; Ridge, JA; Saba, NF; Salama, JK; Smith, RV; Yeung, AR; Beitler, JJ
MLA Citation
McDonald, M. W., et al. “American College of Radiology Appropriateness Criteria on retreatment of recurrent head-and-neck cancer after prior definitive radiation.” International Journal of Radiation Oncology Biology Physics, vol. 82, no. 4, Mar. 2012, pp. 1315–16. Scopus, doi:10.1016/j.ijrobp.2011.10.041.
Source
scopus
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
82
Issue
4
Publish Date
2012
Start Page
1315
End Page
1316
DOI
10.1016/j.ijrobp.2011.10.041

Hypofractionated image-guided radiation therapy for patients with limited volume metastatic non-small cell lung cancer.

INTRODUCTION: Outcomes data treating patients with oligometastatic (≤ 5 metastases) non-small cell lung carcinoma (NSCLC) with hypofractionated image-guided radiotherapy (HIGRT) are limited. METHODS: Consecutive oligometastatic NSCLC patients were reviewed from a prospective database. Patients were included if all active diseases were treated with HIGRT. Lesions that had received prior radiation or had radiographic/metabolic resolution after chemotherapy were not treated with HIGRT. Local control of all treated lesions, distant control, progression-free survival (PFS), overall survival (OS), and control of individual lesions (LeC) were calculated. RESULTS: Twenty-five patients with median of 2 treated oligometastatic lesions were included. Median follow-up was 14 months. Median age was 66 years. Nineteen patients received systemic therapy before HIGRT and 11 had progressive disease after their most recent systemic therapy before HIGRT. Median OS and PFS were 22.7 and 7.6 months. The 18 months local control, distant control, OS, and PFS were 66.1%, 31.7%, 52.9%, and 28.0%. Greater than two sites treated with HIGRT, nonadenocarcinoma histology, prior systemic therapy, and progression after systemic therapy were associated with worse PFS. Sixty-two individual lesions of median size 2.7 cm were treated. For extracranial lesions, median total and fraction dose were 50 and 5 Gy. Median standard equivalent dose in 2 Gy fractions for extracranial lesions was 64.6 Gy yielding 18 months LeC of 70.7%. Standard equivalent dose ≥64.6 Gy increased LeC (p = 0.04). Two patients experienced grade 3 toxicity. CONCLUSIONS: HIGRT for oligometastatic NSCLC provides durable LeC and may provide long-term PFS in some patients. Future HIGRT studies should optimize patient selection and integration with systemic therapy.

Authors
Hasselle, MD; Haraf, DJ; Rusthoven, KE; Golden, DW; Salgia, R; Villaflor, VM; Shah, N; Hoffman, PC; Chmura, SJ; Connell, PP; Vokes, EE; Weichselbaum, RR; Salama, JK
MLA Citation
Hasselle, Michael D., et al. “Hypofractionated image-guided radiation therapy for patients with limited volume metastatic non-small cell lung cancer..” J Thorac Oncol, vol. 7, no. 2, Feb. 2012, pp. 376–81. Pubmed, doi:10.1097/JTO.0b013e31824166a5.
PMID
22198429
Source
pubmed
Published In
J Thorac Oncol
Volume
7
Issue
2
Publish Date
2012
Start Page
376
End Page
381
DOI
10.1097/JTO.0b013e31824166a5

A call for the aggressive treatment of oligometastatic and oligo-recurrent non-small cell lung cancer.

Metastatic non-small cell lung cancer (NSCLC) carries a dismal prognosis. Clinical evidence suggests the existence of an intermediate, or oligometastatic, state when metastases are limited in number and/or location. In addition, following initial curative therapy, many patients present with limited metastatic disease, or oligo-recurrence. Metastasis-directed, anti-cancer therapies may benefit these patients. A growing evidence-base supports the use of hypofractionated, image-guided radiotherapy (HIGRT) for a variety of malignant conditions including inoperable stage I NSCLC and many metastatic sites. When surgical resection is not possible, HIGRT offers an effective alternative for local treatment of limited metastatic disease. Early studies have produced promising results when HIGRT was delivered to all known sites of disease in patients with oligometastatic/oligo-recurrent NSCLC. In a population of patients formerly considered rapidly terminal, these studies report five year overall survival rates of 13-22%. HIGRT for metastatic NSCLC warrants further study. We call for large, intergroup, and even international randomized trials incorporating HIGRT and other metastasis-directed therapies into the treatment of patients with oligometastatic/oligo-recurrent NSCLC.

Authors
Patel, PR; Yoo, DS; Niibe, Y; Urbanic, JJ; Salama, JK
MLA Citation
Patel, Pretesh R., et al. “A call for the aggressive treatment of oligometastatic and oligo-recurrent non-small cell lung cancer..” Pulm Med, vol. 2012, 2012. Pubmed, doi:10.1155/2012/480961.
PMID
23125927
Source
pubmed
Published In
Pulm Med
Volume
2012
Publish Date
2012
Start Page
480961
DOI
10.1155/2012/480961

Pathologic response rates following definitive dose image-guided chemoradiotherapy and resection for locally advanced non-small cell lung cancer.

INTRODUCTION: Treatment of technically operable, medically fit locoregionally advanced non-small cell lung cancer (NSCLC) patients is a controversial therapeutic challenge. Our group routinely uses a trimodality approach. Recent advances in radiotherapy allow for improved tumor targeting and daily patient positioning. We hypothesized that these technologies would improve pathologic response rates. We analyzed consecutively treated stage IIIA/IIIB NSCLC patients undergoing chemoradiotherapy before major lung resection, with particular attention paid to the impact of advanced technologies. METHODS: Locoregionally advanced NSCLC patients (N2) staged in a multidisciplinary forum with mediastinoscopy were planned to receive platinum-based chemotherapy and 60Gy and major lung resection. Four-dimensional CT (4DCT) and image-guided radiotherapy (IGRT) were used as available. Survival endpoints were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using Cox proportional hazards models. RESULTS: We identified 53 patients from 2/1999 to 2/2010. Median RT dose was 59Gy. 68% underwent lobectomy. Forty-three patients were downstaged pathologically (81%), 38 experienced mediastinal sterilization (72%), and 21 (40%) had complete pathologic response (pCR). 1 and 2 year OS were 85.5% and 61.6%. Superior OS and DFS were associated with nodal downstaging and mediastinal sterilization (pN0). Treatment with IGRT/4DCT in 10 patients resulted in high rates of nodal downstaging (100% vs 77%, p=0.0452), mediastinal sterilization (90% vs 67%, p=0.0769), and pCR (60% vs 35%, p=0.0728). CONCLUSIONS: In selected patients, definitive dose CRT followed by major lung resection results in promising DFS and OS. The use of advanced radiotherapy techniques (4DCT and IGRT) appears to result in promising pathologic response rates.

Authors
Shumway, D; Corbin, K; Salgia, R; Hoffman, P; Villaflor, V; Malik, RM; Haraf, DJ; Vigneswaren, WT; Shaikh, AY; Connell, PP; Ferguson, MK; Salama, JK
MLA Citation
Shumway, D., et al. “Pathologic response rates following definitive dose image-guided chemoradiotherapy and resection for locally advanced non-small cell lung cancer..” Lung Cancer, vol. 74, no. 3, Dec. 2011, pp. 446–50. Pubmed, doi:10.1016/j.lungcan.2011.05.003.
PMID
21676484
Source
pubmed
Published In
Lung Cancer
Volume
74
Issue
3
Publish Date
2011
Start Page
446
End Page
450
DOI
10.1016/j.lungcan.2011.05.003

Pulmonary toxicity in Stage III non-small cell lung cancer patients treated with high-dose (74 Gy) 3-dimensional conformal thoracic radiotherapy and concurrent chemotherapy following induction chemotherapy: a secondary analysis of Cancer and Leukemia Group B (CALGB) trial 30105.

PURPOSE: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. METHODS AND MATERIALS: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. RESULTS: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. CONCLUSIONS: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

Authors
Salama, JK; Stinchcombe, TE; Gu, L; Wang, X; Morano, K; Bogart, JA; Crawford, JC; Socinski, MA; Blackstock, AW; Vokes, EE; Cancer and Leukemia Group B,
MLA Citation
Salama, Joseph K., et al. “Pulmonary toxicity in Stage III non-small cell lung cancer patients treated with high-dose (74 Gy) 3-dimensional conformal thoracic radiotherapy and concurrent chemotherapy following induction chemotherapy: a secondary analysis of Cancer and Leukemia Group B (CALGB) trial 30105..” Int J Radiat Oncol Biol Phys, vol. 81, no. 4, Nov. 2011, pp. e269–74. Pubmed, doi:10.1016/j.ijrobp.2011.01.056.
PMID
21477940
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
81
Issue
4
Publish Date
2011
Start Page
e269
End Page
e274
DOI
10.1016/j.ijrobp.2011.01.056

Phase II trial of pemetrexed-based induction chemotherapy followed by concomitant chemoradiotherapy in previously irradiated patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Concurrent chemoreirradiation therapy (CRRT) offers a therapeutic option for patients with locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that response to induction chemotherapy (IC) would improve outcome and predict increased survival. PATIENTS AND METHODS: Subjects with recurrent SCCHN not amenable to standard therapy were eligible. IC consisted of two 28-day cycles of gemcitabine and pemetrexed on days 1 and 14, followed by surgical resection, if appropriate, and/or CRRT consisting of carboplatin, pemetrexed, and single daily fractionated radiotherapy. RESULTS: Thirty-five subjects were enrolled, 31 were assessable for response, with 11 responders [response rate = 35%; 95% confidence interval (CI) 19.2-54.6]. Among 24 subjects who started CRRT, 11 were assessable for radiographic response, 4 complete response, 2 partial response, and 5 progressive disease. Median progression-free survival and overall survival (OS) were 5.5 months (95% CI 3.6-8.3) and 9.5 months (95% CI 7.2-15.4), respectively. One-year OS was 43% (95% CI 26% to 58%). Subjects who responded to IC had improved survival (P = 0.02). Toxic effects included mucositis, dermatitis, neutropenia, infection, hemorrhage, dehydration, and pain. CONCLUSIONS: The combination of pemetrexed plus gemcitabine was active and well tolerated in recurrent SCCHN. Response to IC may help stratify prognosis and offer an objective and dynamic metric in recurrent SCCHN patients being considered for CRRT.

Authors
Villaflor, VM; Haraf, D; Salama, JK; Kocherginsky, M; Langerman, A; Gomez-Abuin, G; Beniwal, P; Blair, EA; Stenson, KM; Portugal, L; Seiwert, T; Williams, RD; Dekker, AJ; Witt, ME; Vokes, EE; Cohen, EEW
MLA Citation
Villaflor, V. M., et al. “Phase II trial of pemetrexed-based induction chemotherapy followed by concomitant chemoradiotherapy in previously irradiated patients with squamous cell carcinoma of the head and neck..” Ann Oncol, vol. 22, no. 11, Nov. 2011, pp. 2501–07. Pubmed, doi:10.1093/annonc/mdq785.
PMID
21385883
Source
pubmed
Published In
Ann Oncol
Volume
22
Issue
11
Publish Date
2011
Start Page
2501
End Page
2507
DOI
10.1093/annonc/mdq785

Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation.

BACKGROUND: It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT. METHODS: The study cohort comprised previously irradiated patients with nonmetastatic disease from 9 consecutive phase 1 and 2 protocols for poor-prognosis HNC. For all patients, reirradiation (ReRT) was delivered with concurrent chemotherapy. Chemotherapy generally was 5-fluorouracil, hydroxyurea, and a third agent. RESULTS: One hundred sixty-six patients were identified, including 81 patients who underwent surgical resection or debulking before enrollment. The median ReRT dose was 66 gray. After a median follow-up of 53 months among surviving patients, the median overall survival (OS) was 10.3 months. The 2-year rates for OS, disease-free survival, locoregional control, and freedom from distant metastasis were 24.8%, 19.9%, 50.7%, and 61.4%, respectively. Thirty-three patients (19.9%) died of treatment-related toxicity. In subgroup analysis, survival was significantly reduced in patients who received previous concurrent chemoradiotherapy (CRT) compared with patients who were naive to CRT (2-year OS rate, 10.8% vs 28.4%; P = .0043). In multivariable analysis, prior CRT was associated independently with OS along with surgery before protocol treatment, full-dose ReRT, and radiotherapy interval. CONCLUSIONS: CReRT achieved a long-term cure for a small group of patients with recurrent or second primary HNC. Previous treatment with CRT was among the important prognostic factors for survival. Because of the associated risk of severe toxicity, CReRT should be limited only to carefully selected patients.

Authors
Choe, KS; Haraf, DJ; Solanki, A; Cohen, EEW; Seiwert, TY; Stenson, KM; Blair, EA; Portugal, L; Villaflor, VM; Witt, ME; Vokes, EE; Salama, JK
MLA Citation
Choe, Kevin S., et al. “Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation..” Cancer, vol. 117, no. 20, Oct. 2011, pp. 4671–78. Pubmed, doi:10.1002/cncr.26084.
PMID
21671479
Source
pubmed
Published In
Cancer
Volume
117
Issue
20
Publish Date
2011
Start Page
4671
End Page
4678
DOI
10.1002/cncr.26084

A randomized phase II study of 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy compared with bevacizumab plus 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy for intermediate-stage and T4N0-1 head and neck cancers.

INTRODUCTION: We conducted a randomized phase II study to evaluate the impact of adding bevacizumab (B) to 5-fluorouracil (5-FU), hydroxyurea (HU), and radiotherapy (FHX) for intermediate-stage and select T4 head and neck squamous cell cancers (HNSCC). PATIENTS AND METHODS: Eligible patients had newly diagnosed HNSCC. Randomization was 2:1 in favor of BFHX. All patients received 500 mg HU p.o. b.i.d., 600 mg/m(2)/day continuous infusion 5-FU, and b.i.d. radiotherapy with or without bevacizumab 10 mg/kg administered on day 1 of each 14-day cycle. Patients received five cycles consisting of chemoradiotherapy for 5 days followed by 9 days without therapy. RESULTS: Twenty-six patients were enrolled (19 BFHX and 7 FHX). The study was halted following unexpected locoregional progression. Two-year survival was 68%; 89% treated with FHX and 58% (95% confidence interval 33% to 78%) treated with BFHX. Two-year locoregional control was 80% after chemoradiotherapy and 85% after surgical salvage. All locoregional progression occurred in T4 tumors randomized to BFHX. Two patients receiving BFHX died during therapy, and one died shortly after therapy. No catastrophic bleeding events were seen. CONCLUSIONS: Locoregional progression seen in T4N0-1 tumors treated with BFHX was unexpected and led to study termination. The addition of bevacuzimab to chemoradiotherapy for HNSCC should be limited clinical trials.

Authors
Salama, JK; Haraf, DJ; Stenson, KM; Blair, EA; Witt, ME; Williams, R; Kunnavakkam, R; Cohen, EEW; Seiwert, T; Vokes, EE
MLA Citation
Salama, J. K., et al. “A randomized phase II study of 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy compared with bevacizumab plus 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy for intermediate-stage and T4N0-1 head and neck cancers..” Ann Oncol, vol. 22, no. 10, Oct. 2011, pp. 2304–09. Pubmed, doi:10.1093/annonc/mdq736.
PMID
21330337
Source
pubmed
Published In
Ann Oncol
Volume
22
Issue
10
Publish Date
2011
Start Page
2304
End Page
2309
DOI
10.1093/annonc/mdq736

Statin Use and Prostate Cancer Recurrence in Men Treated with Brachytherapy

Authors
Oh, DS; Song, H; Freedland, S; Gerber, L; Patel, P; Lewis, S; Yoo, D; Oleson, J; Salama, JK
MLA Citation
Oh, D. S., et al. “Statin Use and Prostate Cancer Recurrence in Men Treated with Brachytherapy.” International Journal of Radiation Oncology*Biology*Physics, vol. 81, no. 2, Elsevier BV, Oct. 2011, pp. S12–13. Crossref, doi:10.1016/j.ijrobp.2011.06.025.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
2
Publish Date
2011
Start Page
S12
End Page
S13
DOI
10.1016/j.ijrobp.2011.06.025

Patterns Of Progression Following Hypofractionated Image-guided Radiotherapy (HIGRT) To Abdominal Lymph Nodes In Oligometastatic (OM) Patients

Authors
Hasselle, MD; Salama, JK; Tye, KE; Golden, DW; Liauw, SL; Weichselbaum, RR; Malik, R
MLA Citation
Hasselle, M. D., et al. “Patterns Of Progression Following Hypofractionated Image-guided Radiotherapy (HIGRT) To Abdominal Lymph Nodes In Oligometastatic (OM) Patients.” International Journal of Radiation Oncology*Biology*Physics, vol. 81, no. 2, Elsevier BV, 2011, pp. S654–S654. Crossref, doi:10.1016/j.ijrobp.2011.06.1924.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
2
Publish Date
2011
Start Page
S654
End Page
S654
DOI
10.1016/j.ijrobp.2011.06.1924

ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation expert panel on radiation oncology-head and neck cancer.

Recurrent and second primary head-and-neck squamous cell carcinomas arising within or in close proximity to previously irradiated fields are a common clinical challenge. Whereas surgical salvage therapy is recommended for resectable disease, randomized data support the role of postoperative reirradiation in high-risk patients. Definitive reirradiation is an established approach for patients with recurrent disease who are medically or technically inoperable or decline radical surgery. The American College of Radiology Expert Panel on Head and Neck Cancer reviewed the relevant literature addressing re-treatment after prior definitive radiation and developed appropriateness criteria for representative clinical scenarios. Examples of unresectable recurrent disease and microscopic residual disease after salvage surgery were addressed. The panel evaluated the appropriateness of reirradiation, the integration of concurrent chemotherapy, radiation technique, treatment volume, dose, and fractionation. The panel emphasized the importance of patient selection and recommended evaluation and treatment at tertiary-care centers with a head-and-neck oncology team equipped with the resources and experience to manage the complexities and toxicities of re-treatment.

Authors
McDonald, MW; Lawson, J; Garg, MK; Quon, H; Ridge, JA; Saba, N; Salama, JK; Smith, RV; Yeung, AR; Yom, SS; Beitler, JJ; Expert Panel on Radiation Oncology-Head and Neck Cancer,
MLA Citation
McDonald, Mark W., et al. “ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation expert panel on radiation oncology-head and neck cancer..” Int J Radiat Oncol Biol Phys, vol. 80, no. 5, Aug. 2011, pp. 1292–98. Pubmed, doi:10.1016/j.ijrobp.2011.02.014.
PMID
21530100
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
80
Issue
5
Publish Date
2011
Start Page
1292
End Page
1298
DOI
10.1016/j.ijrobp.2011.02.014

Concurrent chemotherapy and intensity-modulated radiotherapy for organ preservation of locoregionally advanced oral cavity cancer.

OBJECTIVES: To report outcomes of oral cavity cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy (chemoIMRT). METHODS: Between 2001 and 2004, 21 patients with oral cavity squamous cell carcinoma underwent definitive chemoIMRT. Sites included were oral tongue (n = 9), floor of mouth (n = 6), buccal mucosa (n = 3), retromolar trigone (n = 2), and hard palate (n = 1). Most had stage III-IV disease (n = 20). The most common regimen was 5 days infusional 5-fluorouracil (600 mg/m(2)/d × 5 days), hydroxyurea (500 mg, PO BID), and 1.5 Gy twice-daily irradiation to 72 to 75 Gy. RESULTS: The median follow-up for surviving patients was 60 months. Treatment failure occurred as follows: local-1, regional-1, and distant metastases-2. The 2- and 5-year estimates of locoregional progression-free survival, disease-free survival, and overall survival were 90% and 90%, 71% and 71%, and 76% and 76%, respectively. Late complications included osteoradionecrosis (3 patients, 14%). CONCLUSIONS: Concurrent chemoIMRT results in promising locoregional control for oral cavity squamous cell carcinomas with acceptable toxicity.

Authors
Pederson, AW; Salama, JK; Witt, ME; Stenson, KM; Blair, EA; Vokes, EE; Haraf, DJ
MLA Citation
Pederson, Aaron W., et al. “Concurrent chemotherapy and intensity-modulated radiotherapy for organ preservation of locoregionally advanced oral cavity cancer..” Am J Clin Oncol, vol. 34, no. 4, Aug. 2011, pp. 356–61. Pubmed, doi:10.1097/COC.0b013e3181e8420b.
PMID
21633289
Source
pubmed
Published In
American Journal of Clinical Oncology
Volume
34
Issue
4
Publish Date
2011
Start Page
356
End Page
361
DOI
10.1097/COC.0b013e3181e8420b

Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies.

BACKGROUND: To report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy. METHODS: From 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m² on d1), infusional 5-fluorouracil (600 mg/m²/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment. RESULTS: Median follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1). CONCLUSIONS: Surgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.

Authors
Pederson, AW; Salama, JK; Haraf, DJ; Witt, ME; Stenson, KM; Portugal, L; Seiwert, T; Villaflor, VM; Cohen, EEW; Vokes, EE; Blair, EA
MLA Citation
Pederson, Aaron W., et al. “Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies..” Head Neck Oncol, vol. 3, July 2011. Pubmed, doi:10.1186/1758-3284-3-31.
PMID
21791072
Source
pubmed
Published In
Head & Neck Oncology
Volume
3
Publish Date
2011
Start Page
31
DOI
10.1186/1758-3284-3-31

ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck.

Locoregional recurrence following surgical resection alone for stage III/IV head and neck cancer is common. Adjuvant radiotherapy has been shown to improve post-operative locoregional control when compared to pre-operative radiotherapy for head and neck cancers. Following surgical resection, adverse pathological features determine the need for adjuvant therapy. High-risk pathologic features include extranodal tumor spread and involved surgical margins. Other adverse pathologic features include T 3-4 tumors, perineural invasion, lymphovascular space invasion, low neck adenopathy, and multiple tumor involved cervical lymph nodes. The standard adjuvant therapies are post-operative radiation therapy or post-operative chemoradiotherapy. Post-operative chemoradiotherapy yields superior locoregional control, progression-free survival, and in some studies, overall survival compared to post-operative radiotherapy for high-risk patients in multiple randomized studies. Pooled analyses of randomized data demonstrate that post-operative concurrent chemoradiotherapy is associated with overall survival benefits for patients with involved surgical margins as well as those with extranodal tumor spread. Post-operative radiotherapy concurrent with cisplatin at 100 mg/m(2) every 21 days is the current standard chemoradiotherapy platform adjuvant head and neck cancer treatment. Post-operative radiotherapy and post-operative chemoradiotherapy radiation treatment volumes are not standardized and should be designed based on the risk of recurrence and clinically occult involvement of head and neck subsites and nodal regions. Evidence supports a post-operative radiotherapy and chemoradiotherapy radiation dose of at least 63 Gy for high-risk patients and at least 57 Gy for low risk patients.

Authors
Expert Panel on Radiation Oncology-Head and Neck, ; Salama, JK; Saba, N; Quon, H; Garg, MK; Lawson, J; McDonald, MW; Ridge, JA; Smith, RV; Yeung, AR; Yom, SS; Beitler, JJ
MLA Citation
Expert Panel on Radiation Oncology-Head and Neck, Jonathan J., et al. “ACR appropriateness criteria® adjuvant therapy for resected squamous cell carcinoma of the head and neck..” Oral Oncol, vol. 47, no. 7, July 2011, pp. 554–59. Pubmed, doi:10.1016/j.oraloncology.2011.05.002.
PMID
21664857
Source
pubmed
Published In
Oral Oncol
Volume
47
Issue
7
Publish Date
2011
Start Page
554
End Page
559
DOI
10.1016/j.oraloncology.2011.05.002

Predictors of pulmonary toxicity in limited-stage (LS) small cell lung cancer (SCLC) patients treated with concurrent chemotherapy (CTX) and high-dose (70 Gy) daily radiotherapy (RT): A pooled analysis of three CALGB studies.

Authors
Salama, JK; Hodgson, L; Pang, H; Green, MR; Urbanic, JJ; Blackstock, AW; Crawford, J; Bogart, J; Vokes, EE
MLA Citation
Salama, J. K., et al. “Predictors of pulmonary toxicity in limited-stage (LS) small cell lung cancer (SCLC) patients treated with concurrent chemotherapy (CTX) and high-dose (70 Gy) daily radiotherapy (RT): A pooled analysis of three CALGB studies..” Journal of Clinical Oncology, vol. 29, no. 15_suppl, American Society of Clinical Oncology (ASCO), May 2011, pp. 7078–7078. Crossref, doi:10.1200/jco.2011.29.15_suppl.7078.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
7078
End Page
7078
DOI
10.1200/jco.2011.29.15_suppl.7078

A randomized phase II trial of cetuximab-based induction chemotherapy followed by concurrent cetuximab, 5-FU, hydroxyurea, and hyperfractionated radiation (CetuxFHX), or cetuximab, cisplatin, and accelerated radiation with concomitant boost (CetuxPX) in patients with locoregionally advanced head and neck cancer (HNC).

Authors
Seiwert, TY; Haraf, DJ; Cohen, EE; Blair, EA; Stenson, K; Salama, JK; Kocherginsky, M; Villaflor, VM; Witt, M; Williams, R; Dekker, A; Vokes, EE
MLA Citation
Seiwert, T. Y., et al. “A randomized phase II trial of cetuximab-based induction chemotherapy followed by concurrent cetuximab, 5-FU, hydroxyurea, and hyperfractionated radiation (CetuxFHX), or cetuximab, cisplatin, and accelerated radiation with concomitant boost (CetuxPX) in patients with locoregionally advanced head and neck cancer (HNC)..” Journal of Clinical Oncology, vol. 29, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2011, pp. 5519–5519. Crossref, doi:10.1200/jco.2011.29.15_suppl.5519.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
5519
End Page
5519
DOI
10.1200/jco.2011.29.15_suppl.5519

Predictors of pulmonary toxicity in limited-stage (LS) small cell lung cancer (SCLC) patients treated with concurrent chemotherapy (CTX) and high-dose (70 Gy) daily radiotherapy (RT): A pooled analysis of three CALGB studies.

7078 Background: Predictors of post CTX-RT pulmonary toxicity in LS-SCLC patients are not well defined. Current guidelines are derived from NSCLC regimens, not accounting for the unique biology of SCLC. We analyzed patients on 3 consecutive CALGB LS-SCLC trials to determine factors predicting for post-treatment pulmonary toxicity. METHODS: Patients treated on CALGB protocols 39808, 30002, 30206, investigating 2 cycles of newer CTX agents (39808: topotecan, paclitaxel; 30002: paclitaxel, oral etopside, oral topotecan; 30206: cisplatin, irinotecan) followed by concurrent carboplatin/etopside and 70 Gy daily RT were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3-5 pulmonary toxicities following CTX-RT. PFT data were not routinely collected and not included in this analysis. RESULTS: 211 patients were treated, 100 patients (39808 n=9, 30002 n=34, 30206 n=57) were evaluable with RT dose-volume parameters and adverse event data. Patient characteristics were balanced between except for those in 30206 with significantly improved baseline PS. Median overall and progression free survival was 22.6 months (95% CI: 18.5-29.4) and 13.9 months (95% CI: 12.6-16.7), respectively. Three patients experienced post-treatment pulmonary toxicity. No patients experienced grade 4-5 pulmonary toxicity. Patients with post-treatment grade 3 pulmonary toxicity were likely to be older (p=0.09) and have a smaller total lung volume (p=0.05). Furthermore, exposure of larger volumes of lung to lower (median V5=70%, p=0.09, median V10=63%, p=0.07), intermediate (median V20=50%, p=0.04) and high (median V60=25%, p=0.01) doses of RT were all associated with grade 3 pulmonary toxicity, as was larger mean lung RT dose (median 31 Gy p=0.02). CONCLUSIONS: Post-treatment pulmonary toxicity following completion of 2 cycles CTX followed by CTX-RT was uncommon. Few events limtied statistical power to draw firm conclusions. Data available suggest that care should be taken to minimize mean lung RT exposure, as well as volumes of low, intermediate and high doses of RT.

Authors
Salama, JK; Hodgson, L; Pang, H; Green, MR; Urbanic, JJ; Blackstock, AW; Crawford, J; Bogart, J; Vokes, EE; CALGB,
MLA Citation
Salama, J. K., et al. “Predictors of pulmonary toxicity in limited-stage (LS) small cell lung cancer (SCLC) patients treated with concurrent chemotherapy (CTX) and high-dose (70 Gy) daily radiotherapy (RT): A pooled analysis of three CALGB studies..” J Clin Oncol, vol. 29, no. 15_suppl, May 2011.
PMID
28020370
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
7078

A randomized phase II trial of cetuximab-based induction chemotherapy followed by concurrent cetuximab, 5-FU, hydroxyurea, and hyperfractionated radiation (CetuxFHX), or cetuximab, cisplatin, and accelerated radiation with concomitant boost (CetuxPX) in patients with locoregionally advanced head and neck cancer (HNC).

5519 Background: Cetuximab is commonly used in combination with either chemotherapy or radiation in the treatment of HNC, although the optimal way to integrate cetuximab with concurrent chemoradiation (CRT) remains unclear. We explored the addition of cetuximab to induction chemotherapy and two established CRT platforms in a randomized phase II trial. METHODS: Patients with locoregionally advanced HNC were treated with cetuximab, carboplatin, paclitaxel induction chemotherapy for 2 cycles. Patients were randomized to A: cetuximab, 5-FU, hydroxyurea, and hyperfractionated week-on week-off RT (72-74Gy) (CetuxFHX), or B: cetuximab, cisplatin, accelerated radiation with concomitant boost (CetuxPX)(72Gy). Primary endpoints were 1- and 2-year progression-free (PFS), and overall survival (OS). RESULTS: 110 patients with locoregionally advanced HNC (108 with Stage IV) were enrolled. 57.3% of patients had oropharyngeal (OP) primaries (A: 49%, B: 66%, p16 staining is pending). Induction response rate was 91.8%. 99.1% of patients developed a rash (≥grade 3 in 16.4%); ≥grade 3 neutropenia developed in 36.3% of patients. Overall 1- and 2-year survival rates were 98.3% and 89.5% in CetuxFHX, and 94.2% and 91.4% in CetuxPX arm, with 21.1months median follow-up (not statistically significant, p=0.27, logrank test). Progression free survival at 1 and 2 years was 86.0% and 82.3% in CetuxFHX, and 95.9% and 89.7% in CetuxPX (p=0.18). Grade ≥3 mucositis was present in 91.1%(A) and 94.3%(B) of patients; grade ≥3 dermatitis in 82.1% and 50.9% of patients. 95% of patients completed therapy. Treatment failures occurred in both OP and non-OP tumors. CONCLUSIONS: Cetuximab-based induction chemotherapy is well tolerated and active. Cetuximab can safely be integrated with both FHX and cisplatin based CRT with acceptable toxicities. Survival is favorable on both study arms suggesting that either platform could be investigated further. Data on HPV versus non-HPV-related tumors will be available.

Authors
Seiwert, TY; Haraf, DJ; Cohen, EE; Blair, EA; Stenson, K; Salama, JK; Kocherginsky, M; Villaflor, VM; Witt, M; Williams, R; Dekker, A; Vokes, EE
MLA Citation
Seiwert, T. Y., et al. “A randomized phase II trial of cetuximab-based induction chemotherapy followed by concurrent cetuximab, 5-FU, hydroxyurea, and hyperfractionated radiation (CetuxFHX), or cetuximab, cisplatin, and accelerated radiation with concomitant boost (CetuxPX) in patients with locoregionally advanced head and neck cancer (HNC)..” J Clin Oncol, vol. 29, no. 15_suppl, May 2011.
PMID
28021429
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
29
Issue
15_suppl
Publish Date
2011
Start Page
5519

SU‐E‐T‐266: Propagation of Human Error within a Radiation Oncology Department

Purpose: To study propagation of human error in EBRT in a small radonc department. Methods:While reporting of medical events is mandatory, reporting of other human errors needs encouragement. A mechanism of voluntary reporting 1 was adopted. Specifically, one coordinator was assigned to collect and de‐identify all non‐medical‐event errors. Each error is categorized according to place of origin, how it was caught, and clinical impact. Each error is assigned severity score on a 5 point scale. The EBRT process is modeled into stages of a mostly serial flow: Front Desk, Nursing, MD Consultation and Rx, CT‐Sim, Treatment Planning, Pre‐Tx Physics Chart Check, Pre‐Tx RTT check, Delivery, Weekly Chart Check, and Completion Physics Chart Check. When an error propagates beyond one stage, its severity gets multiplied 2, 3… times as the missed stages increase. Error Severity SUM = Incidence × Severity Score × Propagation Multiplier. Results: On the map of error propagation are 21 recorded incidences for Jan–Feb of 2011: 17 originated in Delivery, 7 in Treatment Planning. Three errors propagated beyond one stage. The error severity map shows a different pattern of hot spots: Treatment Planning (severity score 22), Delivery (17), MD Consult (10). MD Consult's increased rank in severity is due to its potential to cause medical events. Pre‐Tx Physics Chart Check and Weekly Chart Check are effective error catchers as most errors end in them on the error maps. Conclusions: Map of error propagation can be used to indentify hot spots of error origination and traps for catching errors and thus be an effective tool for quality control. © 2011, American Association of Physicists in Medicine. All rights reserved.

Authors
Song, H; Salama, J
MLA Citation
Song, H., and J. Salama. “SU‐E‐T‐266: Propagation of Human Error within a Radiation Oncology Department.” Medical Physics, vol. 38, no. 6, 2011. Scopus, doi:10.1118/1.3612217.
Source
scopus
Published In
Medical Physics
Volume
38
Issue
6
Publish Date
2011
Start Page
3548
DOI
10.1118/1.3612217

MicroRNA expression characterizes oligometastasis(es).

BACKGROUND: Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤ 5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy. METHODS: Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy. RESULTS: Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression. CONCLUSIONS: These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.

Authors
Lussier, YA; Xing, HR; Salama, JK; Khodarev, NN; Huang, Y; Zhang, Q; Khan, SA; Yang, X; Hasselle, MD; Darga, TE; Malik, R; Fan, H; Perakis, S; Filippo, M; Corbin, K; Lee, Y; Posner, MC; Chmura, SJ; Hellman, S; Weichselbaum, RR
MLA Citation
Lussier, Yves A., et al. “MicroRNA expression characterizes oligometastasis(es)..” Plos One, vol. 6, no. 12, 2011. Pubmed, doi:10.1371/journal.pone.0028650.
PMID
22174856
Source
pubmed
Published In
Plos One
Volume
6
Issue
12
Publish Date
2011
Start Page
e28650
DOI
10.1371/journal.pone.0028650

Factors associated with long-term speech and swallowing outcomes after chemoradiotherapy for locoregionally advanced head and neck cancer.

OBJECTIVE: to identify factors that influence patient-centered measures of speech and swallowing function after successful use of chemoradiotherapy to treat cancers of the head and neck. DESIGN: patients previously enrolled in a phase 2 trial using induction chemotherapy consisting of carboplatin and paclitaxel followed by chemoradiotherapy with paclitaxel, fluorouracil, hydroxyurea, and 1 of 3 radiation dose levels were assigned speaking and swallowing scores at follow-up ranging from 1 to 4, with 1 representing normal speech or swallowing and 4 representing significant sustained deficits. PATIENTS: one hundred eighty-four patients with locoregionally advanced head and neck cancer. MAIN OUTCOME MEASURES: speech and swallowing function after chemoradiotherapy. RESULTS: of the 222 patients originally enrolled in the trial, 184 were alive and free of locoregional recurrence at the outset of this study. Of these eligible patients, 163 (88.6%) were assigned a speaking score of 1 through 4 at an average of 34.8 (range, 1.5-76.4) months after completion of treatment, whereas 166 patients (90.2%) were assigned a swallowing score of 1 through 4 at an average of 34.5 (range, 1.0-76.4) months after completion of treatment. Most patients (84.7% with speaking scores and 63.3% with swallowing scores) had no residual deficit and were assigned scores of 1. Factors that were associated with worse speaking outcomes included female sex, smoking history, hypopharyngeal or laryngeal primary sites, and poor response to induction chemotherapy; factors associated with worse swallowing outcomes included advanced patient age, poor performance status, primary site, and neck dissection. CONCLUSIONS: among patients successfully treated for locoregionally advanced cancers of the head and neck, several factors correlate with speaking and swallowing outcomes. Because advances in therapy have led to improved survival in these patients, understanding and controlling adverse effects of treatment should continue to be an active area of investigation.

Authors
Mouw, KW; Haraf, DJ; Stenson, KM; Cohen, EE; Xi, X; Witt, ME; List, M; Blair, EA; Vokes, EE; Salama, JK
MLA Citation
Mouw, Kent W., et al. “Factors associated with long-term speech and swallowing outcomes after chemoradiotherapy for locoregionally advanced head and neck cancer..” Arch Otolaryngol Head Neck Surg, vol. 136, no. 12, Dec. 2010, pp. 1226–34. Pubmed, doi:10.1001/archoto.2010.218.
PMID
21173372
Source
pubmed
Published In
Archives of Otolaryngology Head and Neck Surgery
Volume
136
Issue
12
Publish Date
2010
Start Page
1226
End Page
1234
DOI
10.1001/archoto.2010.218

Chemoradiotherapy for locoregionally advanced squamous cell carcinoma of the base of tongue.

BACKGROUND: Our aim was to report the outcomes of base of tongue cancers treated with chemoradiotherapy. METHODS: Between 1990 and 2004, 127 patients with stage III or IV base of tongue cancer were treated with chemoradiotherapy on protocol. Indications included nodal involvement, T3/T4 tumors, positive margins, those patients refusing surgery, or were medically inoperable. The most common regimen was paclitaxel (100 mg/m2 on day 1), infusional 5-fluorouracil (600 mg/m2/day × 5 days), hydroxyurea (500 mg prescribed orally [PO] 2 × daily [BID]), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment. RESULTS: Median follow-up was 51 months. The median dose to gross tumor was 72.5 Gy (range, 40-75.5 Gy). Five-year locoregional progression-free survival, overall survival, and disease-free survival was 87.0%, 58.2%, and 46.0%, respectively. CONCLUSION: Concurrent chemoradiotherapy results in promising locoregional control for base of tongue cancer. As distant relapse was common, further investigation of systemic therapy with novel agents may be warranted.

Authors
Pederson, AW; Haraf, DJ; Witt, M-E; Stenson, KM; Vokes, EE; Blair, EA; Salama, JK
MLA Citation
Pederson, Aaron W., et al. “Chemoradiotherapy for locoregionally advanced squamous cell carcinoma of the base of tongue..” Head Neck, vol. 32, no. 11, Nov. 2010, pp. 1519–27. Pubmed, doi:10.1002/hed.21360.
PMID
20187015
Source
pubmed
Published In
Head Neck
Volume
32
Issue
11
Publish Date
2010
Start Page
1519
End Page
1527
DOI
10.1002/hed.21360

Adjuvant chemotherapy prior to postoperative concurrent chemoradiotherapy for locoregionally advanced head and neck cancer.

BACKGROUND AND PURPOSE: Induction chemotherapy prior to definitive concurrent chemoradiotherapy (CCRT) is a promising treatment option for unresectable head and neck cancer (HNC). In the postoperative setting, the efficacy of such an approach with adjuvant chemotherapy (AdjCT) followed by postoperative CCRT is unclear. MATERIALS AND METHODS: Forty-one postoperative patients with stage III-IV (M0) HNC enrolled on 3 consecutive phase II clinical trials were retrospectively analyzed. Twenty-five of the patients were treated on a protocol which included AdjCT with carboplatin and paclitaxel prior to postoperative CCRT (AdjCT group). Sixteen were treated on protocols with similar postoperative CCRT but without AdjCT (control group). CCRT consisted of paclitaxel, 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy. RESULTS: After a median follow-up of 72 months, there were no locoregional failures (LRF) or distant metastases (DM) in the AdjCT group. In the control group, there were 2 LRF and 2 DM. The 5-year risk of disease recurrence was 0% in the AdjCT group, compared to 28.9% in the control group (p=0.0074). No patients had disease progression during AdjCT, and all proceeded to postoperative CCRT without delay. CONCLUSIONS: Adjuvant chemotherapy after surgery followed by CCRT may be a treatment strategy associated with favorable disease outcomes in locoregionally advanced HNC. These results pose a hypothesis which warrants further investigation.

Authors
Choe, KS; Salama, JK; Stenson, KM; Blair, EA; Witt, ME; Cohen, EEW; Haraf, DJ; Vokes, EE
MLA Citation
Choe, Kevin S., et al. “Adjuvant chemotherapy prior to postoperative concurrent chemoradiotherapy for locoregionally advanced head and neck cancer..” Radiother Oncol, vol. 97, no. 2, Nov. 2010, pp. 318–21. Pubmed, doi:10.1016/j.radonc.2010.09.003.
PMID
20934766
Source
pubmed
Published In
Radiother Oncol
Volume
97
Issue
2
Publish Date
2010
Start Page
318
End Page
321
DOI
10.1016/j.radonc.2010.09.003

Hypofractionated Image Guided Radiotherapy for Large Volume Oligometastases

Authors
Corbin, KS; Ranck, MC; Hasselle, M; Golden, DW; Partouche, J; Wu, T; Weichselbaum, RR; Salama, JK
MLA Citation
Corbin, K. S., et al. “Hypofractionated Image Guided Radiotherapy for Large Volume Oligometastases.” International Journal of Radiation Oncology*Biology*Physics, vol. 78, no. 3, Elsevier BV, 2010, pp. S582–83. Crossref, doi:10.1016/j.ijrobp.2010.07.1358.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S582
End Page
S583
DOI
10.1016/j.ijrobp.2010.07.1358

Analysis of Radiation Pneumonitis (RP) Incidence in a Phase I Stereotactic Body Radiotherapy (SBRT) Dose Escalation Study for Multiple Metastases

Authors
Yenice, KM; Partouche, J; Cunliffe, A; Farrey, K; Weichselbaum, RR; Salama, JK
MLA Citation
Yenice, K. M., et al. “Analysis of Radiation Pneumonitis (RP) Incidence in a Phase I Stereotactic Body Radiotherapy (SBRT) Dose Escalation Study for Multiple Metastases.” International Journal of Radiation Oncology*Biology*Physics, vol. 78, no. 3, Elsevier BV, 2010, pp. S25–S25. Crossref, doi:10.1016/j.ijrobp.2010.07.098.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S25
End Page
S25
DOI
10.1016/j.ijrobp.2010.07.098

Hypofractionated Image-guided Radiation Therapy in the Treatment of Oligometastatic Renal Cell Carcinoma

Authors
Ranck, MC; Corbin, KS; Golden, DW; Liauw, SL; Weichselbaum, RR; Salama, JK
MLA Citation
Ranck, M. C., et al. “Hypofractionated Image-guided Radiation Therapy in the Treatment of Oligometastatic Renal Cell Carcinoma.” International Journal of Radiation Oncology*Biology*Physics, vol. 78, no. 3, Elsevier BV, 2010, pp. S392–S392. Crossref, doi:10.1016/j.ijrobp.2010.07.925.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S392
End Page
S392
DOI
10.1016/j.ijrobp.2010.07.925

Cone-Beam CT (CBCT) May be Necessary to Ensure Planned Spinal Cord Doses are not Exceeded in Head and Neck (H&N) Patients Treated with Intensity Modulated Radiotherapy (IMRT)

Authors
Farrey, K; Sadinski, M; Golden, DW; Redler, G; Yenice, KM; Haraf, DJ; Pelizzari, CA; Salama, JK; Al-Hallaq, HA
MLA Citation
Farrey, K., et al. “Cone-Beam CT (CBCT) May be Necessary to Ensure Planned Spinal Cord Doses are not Exceeded in Head and Neck (H&N) Patients Treated with Intensity Modulated Radiotherapy (IMRT).” International Journal of Radiation Oncology*Biology*Physics, vol. 78, no. 3, Elsevier BV, 2010, pp. S680–S680. Crossref, doi:10.1016/j.ijrobp.2010.07.1580.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S680
End Page
S680
DOI
10.1016/j.ijrobp.2010.07.1580

Impact of Induction Chemotherapy on Treatment Outcomes in Locoregionally Advanced Head and Neck Carcinoma Patients Treated with Concurrent Chemotherapy and Hyperfractionated Radiotherapy

Authors
Malik, R; Pederson, AW; Choe, KS; Witt, ME; Salama, JK; Cohen, EE; Blair, EA; Stenson, KM; Vokes, EE; Haraf, DJ
MLA Citation
Malik, R., et al. “Impact of Induction Chemotherapy on Treatment Outcomes in Locoregionally Advanced Head and Neck Carcinoma Patients Treated with Concurrent Chemotherapy and Hyperfractionated Radiotherapy.” International Journal of Radiation Oncology*Biology*Physics, vol. 78, no. 3, Elsevier BV, 2010, pp. S435–S435. Crossref, doi:10.1016/j.ijrobp.2010.07.1023.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
78
Issue
3
Publish Date
2010
Start Page
S435
End Page
S435
DOI
10.1016/j.ijrobp.2010.07.1023

Epidermal growth factor receptor inhibitor gefitinib added to chemoradiotherapy in locally advanced head and neck cancer.

PURPOSE: Assess efficacy and toxicity of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, added to, and in maintenance after, concurrent chemoradiotherapy (CCRT) in locally advanced head and neck cancer (LA-HNC) and correlate outcomes with EGFR gene copy number alterations. PATIENTS AND METHODS: Patients with stage III to IV LA-HNC received two cycles of carboplatin/paclitaxel induction chemotherapy (IC) followed by split-course CCRT with fluorouracil, hydroxyurea, twice daily radiotherapy (FHX), and gefitinib (250 mg daily) followed by continued gefitinib for 2 years total. The primary end point was complete response (CR) rate after CCRT. EGFR gene copy number was assessed by fluorescent in situ hybridization. RESULTS: Sixty-nine patients (66 with stage IV disease, 37 with oropharynx primary tumors, and 67 with performance status 0 to 1) were enrolled with a median age of 55 years. Predominant grade 3 or 4 toxicities during IC and CCRT were neutropenia (n = 20) and in-field mucositis (n = 59) and dermatitis (n = 23), respectively. CR rate after CCRT was 90%. After median follow-up of 3.5 years, 4-year overall, progression-free, and disease-specific survival rates were 74%, 72%, and 89%, respectively. To date, one patient has developed a second primary tumor in the aerodigestive tract. In 31 patients with available tissue, high EGFR gene copy number was associated with worse overall survival (P = .02). CONCLUSION: Gefitinib can be administered with FHX and as maintenance therapy for at least 2 years, demonstrating CR and survival rates that compare favorably with prior experience. High EGFR gene copy number may be associated with poor outcome in patients with LA-HNC treated with this regimen.

Authors
Cohen, EEW; Haraf, DJ; Kunnavakkam, R; Stenson, KM; Blair, EA; Brockstein, B; Lester, EP; Salama, JK; Dekker, A; Williams, R; Witt, ME; Grushko, TA; Dignam, JJ; Lingen, MW; Olopade, OI; Vokes, EE
MLA Citation
Cohen, Ezra E. W., et al. “Epidermal growth factor receptor inhibitor gefitinib added to chemoradiotherapy in locally advanced head and neck cancer..” J Clin Oncol, vol. 28, no. 20, July 2010, pp. 3336–43. Pubmed, doi:10.1200/JCO.2009.27.0397.
PMID
20498391
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Issue
20
Publish Date
2010
Start Page
3336
End Page
3343
DOI
10.1200/JCO.2009.27.0397

Tumor necrosis and cavitation after stereotactic body radiation therapy.

Authors
Devisetty, K; Salama, JK
MLA Citation
Devisetty, Kiran, and Joseph K. Salama. “Tumor necrosis and cavitation after stereotactic body radiation therapy..” J Thorac Oncol, vol. 5, no. 7, July 2010, pp. 1100–02. Pubmed, doi:10.1097/JTO.0b013e3181d899d7.
PMID
20581578
Source
pubmed
Published In
J Thorac Oncol
Volume
5
Issue
7
Publish Date
2010
Start Page
1100
End Page
1102
DOI
10.1097/JTO.0b013e3181d899d7

Chemoreirradiation for recurrent salivary gland malignancies.

BACKGROUND AND PURPOSE: To report our experience in treating recurrent salivary gland malignancies using concurrent chemotherapy and reirradiation. MATERIALS AND METHODS: Between 1986 and 2007, 14 patients with locoregionally recurrent salivary gland cancer underwent maximal surgical resection followed by adjuvant 5-fluorouracil and hydroxyurea-based chemotherapy concurrently with 1.5Gy twice daily or 2Gy daily reirradiation. Each cycle consisted of chemoreirradiation for 5 consecutive days followed by a 9-day break. The median reirradiation dose was 66Gy (R 30-72Gy) after a mean radiation treatment interval of 48 months. RESULTS: The median follow-up for all patients was 18 months (R 2-125 months) and 41 months for survivors. The parotid gland (n=6) and minor salivary glands (n=6) were involved more commonly than the submandibular gland (n=2). Locoregional control at 1 and 3years was 72.2% and 51.6%, respectively. Actuarial overall survival at 3 and 5 years was 35.7% and 26.8%, respectively. Tracheostomies and feeding tubes were placed in 2 and 8 patients, respectively. Six patients had feeding tubes at last follow-up or death. CONCLUSIONS: Concurrent chemotherapy and reirradiation for recurrent salivary malignancies result in promising locoregional control for patients with recurrent salivary gland malignancies.

Authors
Pederson, AW; Haraf, DJ; Blair, EA; Stenson, KM; Witt, M-E; Vokes, EE; Salama, JK
MLA Citation
Pederson, Aaron W., et al. “Chemoreirradiation for recurrent salivary gland malignancies..” Radiother Oncol, vol. 95, no. 3, June 2010, pp. 308–11. Pubmed, doi:10.1016/j.radonc.2010.03.006.
PMID
20385414
Source
pubmed
Published In
Radiother Oncol
Volume
95
Issue
3
Publish Date
2010
Start Page
308
End Page
311
DOI
10.1016/j.radonc.2010.03.006

Routine versus clinically indicated post-treatment surveillance in head and neck cancer.

Authors
Iyengar, NM; Salama, JK; Stenson, K; Haraf, DJ; Blair, EA; Vokes, EE; Cohen, EE
MLA Citation
Iyengar, N. M., et al. “Routine versus clinically indicated post-treatment surveillance in head and neck cancer..” Journal of Clinical Oncology, vol. 28, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2010, pp. 5601–5601. Crossref, doi:10.1200/jco.2010.28.15_suppl.5601.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
28
Issue
15_suppl
Publish Date
2010
Start Page
5601
End Page
5601
DOI
10.1200/jco.2010.28.15_suppl.5601

Hypofractionated radiotherapy for oligometastatic non-small cell lung carcinoma.

Authors
Hasselle, MD; Rusthoven, KE; Macrie, BD; Shah, N; Golden, DW; Weichselbaum, RR; Salama, JK
MLA Citation
Hasselle, M. D., et al. “Hypofractionated radiotherapy for oligometastatic non-small cell lung carcinoma..” Journal of Clinical Oncology, vol. 28, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2010, pp. e18049–e18049. Crossref, doi:10.1200/jco.2010.28.15_suppl.e18049.
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
28
Issue
15_suppl
Publish Date
2010
Start Page
e18049
End Page
e18049
DOI
10.1200/jco.2010.28.15_suppl.e18049

ACR Appropriateness Criteria: local-regional therapy for resectable oropharyngeal squamous cell carcinomas.

The optimal management of resectable oropharyngeal squamous cell carcinomas is controversial with many treatment options, both surgical and nonsurgical approaches, supported by published experiences with no randomized trials comparing commonly accepted treatments. The treatment decisions are further complicated by the need for local-regional disease control and competing goals to preserve salivary and swallow function. Treatment decisions may also be affected by tumor and patient related factors and a history of environmental exposure to tobacco and evidence of human papilloma virus. We summarize the published literature and provide treatment consensus derived from the modified Delphi methodology.

Authors
Quon, H; Yom, SS; Garg, MK; Lawson, J; McDonald, MW; Ridge, JA; Saba, N; Salama, J; Smith, R; Yeung, AR; Beitler, JJ
MLA Citation
Quon, Harry, et al. “ACR Appropriateness Criteria: local-regional therapy for resectable oropharyngeal squamous cell carcinomas..” Curr Probl Cancer, vol. 34, no. 3, May 2010, pp. 175–92. Pubmed, doi:10.1016/j.currproblcancer.2010.04.004.
PMID
20541056
Source
pubmed
Published In
Curr Probl Cancer
Volume
34
Issue
3
Publish Date
2010
Start Page
175
End Page
192
DOI
10.1016/j.currproblcancer.2010.04.004

Predictors of competing mortality in advanced head and neck cancer.

PURPOSE Death from noncancer causes (competing mortality) is an important event in head and neck cancer, but studies identifying predictors of this event are lacking. We sought to identify predictors of competing mortality and develop a risk stratification model for competing events. PATIENTS AND METHODS Cohort study of 479 patients with stage III to IV carcinoma of the head and neck diagnosed between August 1993 and November 2004. Patients were treated on consecutive prospective clinical trials involving organ-preserving chemoradiotherapy and surgery. We used multivariable competing risks regression models to analyze factors associated with the cumulative incidence of competing mortality, locoregional and distant failure, and second malignancies as first events. Results Median follow-up was 52 months median for survivors. The 5-year cumulative incidence of competing mortality was 19.6% (95% CI, 15.8 to 23.4). On multivariable analysis, competing mortality was associated with female sex (hazard ratio [HR], 1.72; 95% CI, 1.13 to 2.63), increasing age (HR, 1.30; 95% CI, 1.04 to 1.62), increasing Charlson Comorbidity Index (HR, 1.24; 95% CI, 1.05 to 1.47), decreasing body mass index (HR, 0.33; 95% CI, 0.13 to 0.84), and decreasing distance traveled to the treating center (HR, 0.65; 95% CI, 0.44 to 0.98). Patients with zero, one, two, and > or = three risk factors had 5-year competing mortality of 8.9% (95% CI, 3.0% to 14.8%), 12.4% (95% CI, 7.0% to 17.8%), 22.1% (95% CI, 14.5% to 29.7%), and 39.3% (95% CI, 28.6% to 50.1%), respectively. CONCLUSION Competing mortality in advanced head and neck cancer is associated with several demographic and health status characteristics. Analyses of risk factors for competing mortality may be useful in outcomes reporting and designing clinical trials.

Authors
Mell, LK; Dignam, JJ; Salama, JK; Cohen, EEW; Polite, BN; Dandekar, V; Bhate, AD; Witt, ME; Haraf, DJ; Mittal, BB; Vokes, EE; Weichselbaum, RR
MLA Citation
Mell, Loren K., et al. “Predictors of competing mortality in advanced head and neck cancer..” J Clin Oncol, vol. 28, no. 1, Jan. 2010, pp. 15–20. Pubmed, doi:10.1200/JCO.2008.20.9288.
PMID
19933920
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Issue
1
Publish Date
2010
Start Page
15
End Page
20
DOI
10.1200/JCO.2008.20.9288

Chemoradiation for patients with advanced oral cavity cancer.

OBJECTIVES/HYPOTHESIS: Patients with advanced oral cavity cancer (OCC) typically have not been enrolled in clinical trials utilizing contemporary multimodality strategies. There exist dogmatic expectations of inferior outcome in OCC patients secondary to ineffectiveness of treatment and unacceptable toxicity. The purpose of this study was to analyze survival, swallowing function, and incidence of osteoradionecrosis (ORN) of patients with stage III/IV OCC who have undergone primary concomitant chemoradiotherapy (CRT). METHODS: All advanced OCC patients who were enrolled in University of Chicago concomitant CRT protocols from 1994 to 2008 were reviewed. One hundred eleven newly diagnosed advanced OCC patients were evaluated. We performed a subset analysis of 27 additional advanced OCC patients who underwent surgery followed by postoperative CRT. Swallowing function was assessed via oropharyngeal motility study, and a Swallowing Performance Status Scale score was assigned. Presence of clinically significant ORN was documented. RESULTS: Median follow-up was 3.25 years. Five-year overall and progression-free survival was 66.9% and 65.9%, respectively. There was no difference in overall or progression-free survival when the surgery-first group was compared with the primary CRT group (P = .88 and P = .86 respectively). Function, without gastric tube requirement, was excellent, with 92.2% of patients able to maintain weight via oral route. Incidence of ORN was 18.4%, occurring in nine of 49 patients evaluated. CONCLUSIONS: Our data support the use of primary CRT as a viable treatment option for patients with advanced OCC. Survival is high, and overall function for the majority of patients is satisfactory. Patients with T4 oral tongue cancer may be spared total glossectomy. The incidence of ORN may be considered acceptable, in light of the benefits of enduring life and function.

Authors
Stenson, KM; Kunnavakkam, R; Cohen, EEW; Portugal, LD; Blair, E; Haraf, DJ; Salama, J; Vokes, EE
MLA Citation
Stenson, Kerstin M., et al. “Chemoradiation for patients with advanced oral cavity cancer..” Laryngoscope, vol. 120, no. 1, Jan. 2010, pp. 93–99. Pubmed, doi:10.1002/lary.20716.
PMID
19856305
Source
pubmed
Published In
Laryngoscope
Volume
120
Issue
1
Publish Date
2010
Start Page
93
End Page
99
DOI
10.1002/lary.20716

Clinical practice guidance for radiotherapy planning after induction chemotherapy in locoregionally advanced head-and-neck cancer.

PURPOSE: The use of induction chemotherapy (IC) for locoregionally advanced head-and-neck cancer is increasing. The response to IC often causes significant alterations in tumor volume and location and shifts in normal anatomy. Proper determination of the radiotherapy (RT) targets after IC becomes challenging, especially with the use of conformal and precision RT techniques. Therefore, a consensus conference was convened to discuss issues related to RT planning and coordination of care for patients receiving IC. METHODS AND MATERIALS: Ten participants with special expertise in the various aspects of integration of IC and RT for the treatment of locoregionally advanced head-and-neck cancer, including radiation oncologists, medical oncologists, and a medical physicist, participated. The individual members were assigned topics for focused, didactic presentations. Discussion was encouraged after each presentation, and recommendations were formulated. RESULTS: Recommendations and guidelines emerged that emphasize up-front evaluation by all members of the head-and-neck management team, high-quality baseline and postinduction planning scans with the patient in the treatment position, the use of preinduction target volumes, and the use of full-dose RT, even in the face of a complete response. CONCLUSION: A multidisciplinary approach is strongly encouraged. Although these recommendations were provided primarily for patients treated with IC, many of these same principles apply to concurrent chemoradiotherapy without IC. A rapid response during RT is quite common, requiring the development of two or more plans in a sizeable fraction of patients, and suggesting the need for similar guidance in the rapidly evolving area of adaptive RT.

Authors
Salama, JK; Haddad, RI; Kies, MS; Busse, PM; Dong, L; Brizel, DM; Eisbruch, A; Tishler, RB; Trotti, AM; Garden, AS
MLA Citation
Salama, Joseph K., et al. “Clinical practice guidance for radiotherapy planning after induction chemotherapy in locoregionally advanced head-and-neck cancer..” Int J Radiat Oncol Biol Phys, vol. 75, no. 3, Nov. 2009, pp. 725–33. Pubmed, doi:10.1016/j.ijrobp.2008.11.059.
PMID
19362781
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
75
Issue
3
Publish Date
2009
Start Page
725
End Page
733
DOI
10.1016/j.ijrobp.2008.11.059

Neck response to chemoradiotherapy: complete radiographic response correlates with pathologic complete response in locoregionally advanced head and neck cancer.

OBJECTIVE: The role of neck dissection following chemoradiotherapy (CRT) for locoregionally advanced head and neck cancer is an area of active debate. Patients who have a complete radiographic response may not need dissection, and the extent of neck dissection necessary for those patients with residual disease is unclear. DESIGN: Retrospective review of data from a prospectively collected database of patients with locoregionally advanced head and neck cancer treated as part of a phase 2 study of induction chemotherapy followed by concurrent CRT. The results of post-CRT neck computed tomography (CT) imaging and pathologic analysis of the neck dissection specimens were compared to evaluate correlation between radiographic and pathologic response. RESULTS: Forty-nine patients underwent 61 hemineck dissections. Overall, 209 neck levels were dissected. Radiologic complete response in the neck was achieved in 39 patients, all of whom had pathologic specimens negative for tumor cells. Ten patients (20%) had a total of 14 neck levels with residual disease on CT imaging. Five (50%) of these 10 patients were found to have residual tumor cells on pathologic analysis. Tumor cells were contained only to those levels found positive on CT imaging; they were present in 7 (50%) of the 14 positive levels. CONCLUSIONS: Neck levels with residual disease on post-CRT CT imaging warrant removal. However, neck levels without evidence of disease on post-CRT CT imaging are unlikely to harbor cancer, which lends further support to the concept of basing neck dissection on post-CRT staging and performance of limited neck dissections for patients with limited residual disease.

Authors
Langerman, A; Plein, C; Vokes, EE; Salama, JK; Haraf, DJ; Blair, EA; Stenson, KM
MLA Citation
Langerman, Alexander, et al. “Neck response to chemoradiotherapy: complete radiographic response correlates with pathologic complete response in locoregionally advanced head and neck cancer..” Arch Otolaryngol Head Neck Surg, vol. 135, no. 11, Nov. 2009, pp. 1133–36. Pubmed, doi:10.1001/archoto.2009.154.
PMID
19917927
Source
pubmed
Published In
Archives of Otolaryngology Head and Neck Surgery
Volume
135
Issue
11
Publish Date
2009
Start Page
1133
End Page
1136
DOI
10.1001/archoto.2009.154

A multi-institutional acute gastrointestinal toxicity analysis of anal cancer patients treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.

Using previous dosimetric analysis methods, we identified the volume of bowel receiving 30 Gy (V(30)) correlated with acute gastrointestinal (GI) toxicity in anal cancer patients treated with intensity-modulated radiation therapy and concurrent chemotherapy. For V(30)>450 cc and < or =450 cc, acute GI toxicity was 33% and 8%, respectively (p=0.003).

Authors
Devisetty, K; Mell, LK; Salama, JK; Schomas, DA; Miller, RC; Jani, AB; Roeske, JC; Aydogan, B; Chmura, SJ
MLA Citation
Devisetty, Kiran, et al. “A multi-institutional acute gastrointestinal toxicity analysis of anal cancer patients treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy..” Radiother Oncol, vol. 93, no. 2, Nov. 2009, pp. 298–301. Pubmed, doi:10.1016/j.radonc.2009.07.006.
PMID
19717198
Source
pubmed
Published In
Radiother Oncol
Volume
93
Issue
2
Publish Date
2009
Start Page
298
End Page
301
DOI
10.1016/j.radonc.2009.07.006

Single Segment Non-coplanar Beam Optimization for Gated Lung SBRT Planning and Delivery

Authors
Partouche, J; Wu, T; Farrey, K; Salama, JK; Yenice, KM
MLA Citation
Partouche, J., et al. “Single Segment Non-coplanar Beam Optimization for Gated Lung SBRT Planning and Delivery.” International Journal of Radiation Oncology*Biology*Physics, vol. 75, no. 3, Elsevier BV, 2009, pp. S672–73. Crossref, doi:10.1016/j.ijrobp.2009.07.1535.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
75
Issue
3
Publish Date
2009
Start Page
S672
End Page
S673
DOI
10.1016/j.ijrobp.2009.07.1535

Correlation of body mass index with toxicity and survival in locoregionally advanced head and neck cancer patients treated with induction chemotherapy and concurrent chemoradiotherapy.

6074 Background: Concurrent chemoradiotherapy (CRT) offers high functional organ preservation rates for locoregionally advanced head and neck cancer (LRAHNC) patients, but is associated with significant acute and chronic speech and swallowing toxicity. Recently, body mass index (BMI) has been suggested as a predictor of head and neck cancer patient outcome. In this analysis we sought to determine the impact of BMI on survival and toxicity outcomes in LRAHNC patients treated with CRT. METHODS: 220 LRAHNC patients were treated on a multiinstitutional protocol consisting of induction carboplatin and paclitaxel followed by CRT. CRT was delivered for 4-5 cycles; each 14-day cycle consisted of 5 days concurrent paclitaxel, continuous infusion 5-FU, hydroxyurea, and 1.5 Gy twice daily radiation followed by 9 days without any treatment. Each patient's pre-treatment BMI was classified as overweight (BMI >= 25) or non-overweight (BMI < 25). As an independent variable, BMI was analyzed as a predictor of IndCT or CRT toxicity, locoregional control, and overall survival. BMI was analyzed as categorical variable, and also a continuous variable in a multivariate proportional hazards model. RESULTS: There was no association between BMI and IndCT toxicity. During CRT overweight patients had significantly lower rates (24/103 vs 42/112) of grade 3 or higher neutropenia (p = 0.027), mucositis (p = 0.05), dermatitis (p = 0.028) and higher rates of anorexia (p = 0.05). Overweight patients had 12% long term PEG tube rate, compared to 34% of non-overweight patients (p < 0.001). On pooled survival analysis, patients with BMI > 25 had significantly better overall survival outcomes (mean 81.2 months, 95% CI 75.1-87.3 months) than patients with BMI < 25 (median 58.2 months; mean 56.5 months, 95% CI 49.6-63.3 months) (log-rank p < 0.001). CONCLUSIONS: Our data suggest patients with pre-treatment BMI > 25 experience lower rates of toxicity commonly associated with chemoradiation, and have a significantly better prognosis than patients with BMI < 25. Although the mechanism of BMI as an independent predictor of outcomes is unclear, we are continuing to explore mechanisms underlying this association. No significant financial relationships to disclose.

Authors
Jain, AK; Salama, JK; Stenson, KM; Blair, E; Cohen, EE; Witt, M; Haraf, DJ; Vokes, EE
MLA Citation
Jain, A. K., et al. “Correlation of body mass index with toxicity and survival in locoregionally advanced head and neck cancer patients treated with induction chemotherapy and concurrent chemoradiotherapy..” J Clin Oncol, vol. 27, no. 15_suppl, May 2009.
PMID
27961940
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Issue
15_suppl
Publish Date
2009
Start Page
6074

Correlation of body mass index with toxicity and survival in locoregionally advanced head and neck cancer patients treated with induction chemotherapy and concurrent chemoradiotherapy

Authors
Jain, AK; Salama, JK; Stenson, KM; Blair, E; Cohen, EE; Witt, M; Haraf, DJ; Vokes, EE
MLA Citation
Jain, A. K., et al. “Correlation of body mass index with toxicity and survival in locoregionally advanced head and neck cancer patients treated with induction chemotherapy and concurrent chemoradiotherapy.” Journal of Clinical Oncology, vol. 27, no. 15, AMER SOC CLINICAL ONCOLOGY, 2009.
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
27
Issue
15
Publish Date
2009

Advances in radiotherapy for tumors involving the mediastinum.

RT is an integral component of treatment in many tumors of the mediastinum. In recent years, there have been advances in RT planning and delivery, which have allowed more effective radiation delivery while sparing normal tissues. New technologies and radiation modalities may help achieve disease control more safely and effectively.

Authors
Choe, KS; Salama, JK
MLA Citation
Choe, Kevin S., and Joseph K. Salama. “Advances in radiotherapy for tumors involving the mediastinum..” Thorac Surg Clin, vol. 19, no. 1, Feb. 2009, pp. 133–41. Pubmed, doi:10.1016/j.thorsurg.2008.09.010.
PMID
19288828
Source
pubmed
Published In
Thoracic Surgery Clinics
Volume
19
Issue
1
Publish Date
2009
Start Page
133
End Page
141
DOI
10.1016/j.thorsurg.2008.09.010

Calculation and prediction of the effect of respiratory motion on whole breast radiation therapy dose distributions.

The standard treatment technique used for whole-breast irradiation can result in undesirable dose distributions in the treatment site, leading to skin reaction/fibrosis and pulmonary and cardiac toxicities. Hence, the technique has evolved from conventional wedged technique (CWT) to segment intensity-modulated radiation therapy (SIMRT) and beamlet IMRT (IMRT). However, these newer techniques feature more highly modulated dose distributions that may be affected by respiration. The purpose of this work was to conduct a simple study of the clinical impact of respiratory motion on breast radiotherapy dose distributions for the three treatment planning techniques. The ultimate goal was to determine which patients would benefit most from the use of motion management. Eight patients with early-stage breast cancer underwent a free-breathing (FB) computed tomography (CT) simulation, with medial and lateral markers placed on the skin. Two additional CT scans were obtained at the end of inspiration (EI) and the end of expiration (EE). The FB-CT scan was used to develop treatment plans using each technique. Each plan was then applied to EI and EE-CT scans. Compared with the FB CT scan, the medial markers moved up to 1.8 cm in the anterior-superior direction at the end of inspiration (EI-scan), and on average 8 mm. The CWT and SIMRT techniques were not "sensitive" to respiratory motion, because the % clinical target volume (CTV) receiving 95% of the prescription dose (V(95%)) remained constant for both techniques. For patients that had large respiratory motion indicated by marker movement >0.6 cm, differences in coverage of the CTV at the V100% between FB and EI for beamlet IMRT plans were on the order of >10% and up to 18%. A linear model was developed to relate the dosimetric coverage difference introduced by respiration with the motion information. With this model, the dosimetric coverage difference introduced by respiratory motion could be evaluated during patient CT simulation. An appropriate treatment method can be chosen after the simulation.

Authors
Cao, J; Roeske, JC; Chmura, SJ; Salama, JK; Shoushtari, AN; Boyer, AL; Martel, MK
MLA Citation
Cao, Junsheng, et al. “Calculation and prediction of the effect of respiratory motion on whole breast radiation therapy dose distributions..” Med Dosim, vol. 34, no. 2, 2009, pp. 126–32. Pubmed, doi:10.1016/j.meddos.2008.07.002.
PMID
19410141
Source
pubmed
Published In
Med Dosim
Volume
34
Issue
2
Publish Date
2009
Start Page
126
End Page
132
DOI
10.1016/j.meddos.2008.07.002

Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: a multi-institutional phase II trial investigating three radiotherapy dose levels.

BACKGROUND: We hypothesized induction chemotherapy (IndCT) would improve distant control (DC) without compromising locoregional control (LRC) for locoregionally advanced head and neck cancer patients. Additionally, we systematically lowered radiotherapy (RT) doses attempting to maintain LRC while decreasing toxicity. PATIENTS AND METHODS: Stages III-IV (M0) locoregionally advanced head and neck cancer patients received carboplatin/paclitaxel (Taxol) IndCT followed by four or five cycles consisting of 5 days of paclitaxel, fluorouracil, hydroxyurea, and BID RT followed by a nine day break. RT dose to gross disease (high risk), intermediate, and low-risk volumes were reduced from cohort A (n = 68): 75, 60, and 45 Gy; to cohort B (n = 64): 75, 54, and 39 Gy; then cohort C (n = 90): 72, 51, and 36 Gy. RESULTS: A total of 222 patients accrued from November 1998 to September 2002. Median follow-up is 56 months. In all, 93/96/76% achieved a complete response to concurrent chemoradiotherapy (CRT) in cohort A/B/C. Three- and 5-year overall survivals (OSs) are 68% and 62%, respectively. Five-year LRC and DC are 91% and 87%, respectively. Response to IndCT predicted for OS, LRC, and time to progression (TTP). Cohort C patients had similar OS (P = 0.95), LRC, and DC, but worse (TTP) (P = 0.027). CONCLUSIONS: IndCT before CRT reduces distant progression while maintaining high LRC. The cohort B schedule provides the best therapeutic ratio. A randomized trial investigating IndCT before CRT has been initiated.

Authors
Salama, JK; Stenson, KM; Kistner, EO; Mittal, BB; Argiris, A; Witt, ME; Rosen, F; Brockstein, BE; Cohen, EEW; Haraf, DJ; Vokes, EE
MLA Citation
Salama, J. K., et al. “Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: a multi-institutional phase II trial investigating three radiotherapy dose levels..” Ann Oncol, vol. 19, no. 10, Oct. 2008, pp. 1787–94. Pubmed, doi:10.1093/annonc/mdn364.
PMID
18539617
Source
pubmed
Published In
Ann Oncol
Volume
19
Issue
10
Publish Date
2008
Start Page
1787
End Page
1794
DOI
10.1093/annonc/mdn364

Characteristics associated with swallowing changes after concurrent chemotherapy and radiotherapy in patients with head and neck cancer.

OBJECTIVE: To define factors that acutely influenced swallowing function prior to and during concurrent chemotherapy and radiotherapy. DESIGN: A summary score from 1 to 7 (the swallowing performance status scale [SPS]) of oral and pharyngeal impairment, aspiration, and diet, was assigned to each patient study by a single senior speech and swallow pathologist, with higher scores indicating worse swallowing. Generalized linear regression models were formulated to asses the effects of patient factors (performance status, smoking intensity, amount of alcohol ingestion, and age), tumor factors (primary site, T stage, and N stage), and treatment-related factors (radiation dose, use of intensity-modulated radiation therapy, response to induction chemotherapy, postchemoradiotherapy neck dissection, and preprotocol surgery) on the differences between SPS score before and after treatment. SETTING: University hospital tertiary care referral center. PATIENTS: The study included 95 patients treated under a multiple institution, phase 2 protocol who underwent a videofluorographic oropharyngeal motility (OPM) study to assess swallowing function prior to and within 1 to 2 months after the completion of concurrent chemotherapy and radiotherapy. MAIN OUTCOME MEASURES: Factors associated with swallowing changes after chemoradiotherapy. RESULTS: The mean pretreatment and posttreatment OPM scores were 3.09 and 3.77, respectively. Patients with T3 or T4 tumors (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.15-0.95; P = .04) and a performance status of 1 or 2 (OR, 0.37; 95% CI, 0.15-0.91; P = .03) were less likely to have worsening of swallowing after chemoradiotherapy. There was a trend for worse swallowing with increasing age (OR, 1.04; 95% CI, 0.99-1.09; P = .08). Only T stage (T3 or T4) was associated with improved swallowing after treatment (OR, 8.96; 95% CI, 1.9-41.5; P < .001). CONCLUSION: In patients undergoing concurrent chemotherapy and radiotherapy, improved swallowing function over baseline is associated with advanced T stage.

Authors
Salama, JK; Stenson, KM; List, MA; Mell, LK; Maccracken, E; Cohen, EE; Blair, E; Vokes, EE; Haraf, DJ
MLA Citation
Salama, Joseph K., et al. “Characteristics associated with swallowing changes after concurrent chemotherapy and radiotherapy in patients with head and neck cancer..” Arch Otolaryngol Head Neck Surg, vol. 134, no. 10, Oct. 2008, pp. 1060–65. Pubmed, doi:10.1001/archotol.134.10.1060.
PMID
18936351
Source
pubmed
Published In
Archives of Otolaryngology Head and Neck Surgery
Volume
134
Issue
10
Publish Date
2008
Start Page
1060
End Page
1065
DOI
10.1001/archotol.134.10.1060

A rationale for the targeted treatment of oligometastases with radiotherapy.

An oligometastatic state has been proposed wherein patients with metastases limited in number and location may benefit from local therapy directed at all known sites of metastases. We describe here the clinical and biological basis for the oligometastatic state. We present evidence for a potentially curative approach to patients with oligometastases using stereotactic body radiotherapy (SBRT) and we review the literature for SBRT directed at specific metastatic sites in the lungs, liver and multiple organs.

Authors
Macdermed, DM; Weichselbaum, RR; Salama, JK
MLA Citation
Macdermed, Dhara M., et al. “A rationale for the targeted treatment of oligometastases with radiotherapy..” J Surg Oncol, vol. 98, no. 3, Sept. 2008, pp. 202–06. Pubmed, doi:10.1002/jso.21102.
PMID
18618604
Source
pubmed
Published In
J Surg Oncol
Volume
98
Issue
3
Publish Date
2008
Start Page
202
End Page
206
DOI
10.1002/jso.21102

Functional organ preservation with definitive chemoradiotherapy for T4 laryngeal squamous cell carcinoma.

BACKGROUND: Randomized trials established chemoradiotherapy as standard treatment for advanced laryngeal cancer. Patients with large-volume T4 disease (LVT4) were excluded from these trials. The purpose of this study was to report T4 laryngeal cancer patient outcome, including those with LVT4 disease, treated with chemoradiotherapy. PATIENTS AND METHODS: This study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX). RESULTS: Median follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with >or=1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03). CONCLUSIONS: Promising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.

Authors
Knab, BR; Salama, JK; Solanki, A; Stenson, KM; Cohen, EE; Witt, ME; Haraf, DJ; Vokes, EE
MLA Citation
Knab, B. R., et al. “Functional organ preservation with definitive chemoradiotherapy for T4 laryngeal squamous cell carcinoma..” Ann Oncol, vol. 19, no. 9, Sept. 2008, pp. 1650–54. Pubmed, doi:10.1093/annonc/mdn173.
PMID
18467314
Source
pubmed
Published In
Ann Oncol
Volume
19
Issue
9
Publish Date
2008
Start Page
1650
End Page
1654
DOI
10.1093/annonc/mdn173

Pathologic Predictors for Outcome in Recurrent and Second Primary Head and Neck Cancer Patients Undergoing Surgery followed by Concurrent Chemo-reirradiation

Authors
Solanki, A; Stenson, K; Haraf, D; Choe, K; Cohen, E; Seiwert, T; Blair, E; Vokes, E; Salama, JK
MLA Citation
Solanki, A., et al. “Pathologic Predictors for Outcome in Recurrent and Second Primary Head and Neck Cancer Patients Undergoing Surgery followed by Concurrent Chemo-reirradiation.” International Journal of Radiation Oncology*Biology*Physics, vol. 72, no. 1, Elsevier BV, 2008, pp. S402–03. Crossref, doi:10.1016/j.ijrobp.2008.06.1288.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S402
End Page
S403
DOI
10.1016/j.ijrobp.2008.06.1288

Factors Associated with Non-cancer Mortality in Advanced Head and Neck Cancer: A Competing Risks Analysis

Authors
Mell, LK; Dignam, JJ; Salama, JK; Cohen, EE; Polite, BN; Bhate, AD; Haraf, DJ; Mittal, BB; Vokes, EE; Weichselbaum, RR
MLA Citation
Mell, L. K., et al. “Factors Associated with Non-cancer Mortality in Advanced Head and Neck Cancer: A Competing Risks Analysis.” International Journal of Radiation Oncology*Biology*Physics, vol. 72, no. 1, Elsevier BV, 2008, pp. S42–S42. Crossref, doi:10.1016/j.ijrobp.2008.06.859.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S42
End Page
S42
DOI
10.1016/j.ijrobp.2008.06.859

Monte Carlo Evaluation of Stereotactic Body Radiotherapy (SBRT) Treatment Planning for Lung Tumors

Authors
Wu, T; Farrey, K; Salama, JK; Yenice, KM
MLA Citation
Wu, T., et al. “Monte Carlo Evaluation of Stereotactic Body Radiotherapy (SBRT) Treatment Planning for Lung Tumors.” International Journal of Radiation Oncology*Biology*Physics, vol. 72, no. 1, Elsevier BV, 2008, pp. S615–S615. Crossref, doi:10.1016/j.ijrobp.2008.06.249.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S615
End Page
S615
DOI
10.1016/j.ijrobp.2008.06.249

Previous Chemoradiotherapy Predicts for Worse Survival in Patients Undergoing Chemo-reirradiation for Recurrent and Second Primary Head and Neck Cancer

Authors
Choe, KS; Solanki, A; Haraf, DJ; Cohen, EE; Seiwert, TY; Stenson, KM; Blair, E; Witt, M; Vokes, EE; Salama, JK
MLA Citation
Choe, K. S., et al. “Previous Chemoradiotherapy Predicts for Worse Survival in Patients Undergoing Chemo-reirradiation for Recurrent and Second Primary Head and Neck Cancer.” International Journal of Radiation Oncology*Biology*Physics, vol. 72, no. 1, Elsevier BV, 2008, pp. S378–S378. Crossref, doi:10.1016/j.ijrobp.2008.06.1232.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
72
Issue
1
Publish Date
2008
Start Page
S378
End Page
S378
DOI
10.1016/j.ijrobp.2008.06.1232

An initial report of a radiation dose-escalation trial in patients with one to five sites of metastatic disease.

PURPOSE: Previous investigations have suggested that a subset of patients with metastatic cancer in a limited number of organs may benefit from local treatment. We investigated whether cancer patients with limited sites of metastatic disease (oligometastasis) who failed standard therapies could be identified and safely treated at one to five known sites of low-volume disease with radiotherapy. EXPERIMENTAL DESIGN: Patients with one to five sites of metastatic cancer with a life expectancy of >3 months and good performance status received escalating doses of radiation to all known sites of cancer with hypofractionated radiation therapy. Patients were followed radiographically with computed tomography scans of the chest, abdomen, and pelvis and metabolically with [18F]fluorodeoxyglucose-positron emission tomography 1 month following treatment and then every 3 months. Acute toxicities were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and late toxicities were scored using the Radiation Therapy Oncology Group late toxicity scoring system. RESULTS: Twenty-nine patients with 56 metastatic lesions were enrolled from November 2004 to March 2007, with a median follow-up of 14.9 months. Two patients experienced acute (radiation pneumonitis and nausea) and one experienced chronic (gastrointestinal hemorrhage) grade > or =3 toxicity. Fifty-nine percent of patients responded to protocol therapy. Twenty-one percent of patients have not progressed following protocol treatment. Fifty-seven percent of treated lesions have not progressed at last follow-up. Progression was amenable to further local therapy in 48% of patients. CONCLUSIONS: Patients with low-volume metastatic cancer can be identified, safely treated, and may benefit from radiotherapy.

Authors
Salama, JK; Chmura, SJ; Mehta, N; Yenice, KM; Stadler, WM; Vokes, EE; Haraf, DJ; Hellman, S; Weichselbaum, RR
MLA Citation
Salama, Joseph K., et al. “An initial report of a radiation dose-escalation trial in patients with one to five sites of metastatic disease..” Clin Cancer Res, vol. 14, no. 16, Aug. 2008, pp. 5255–59. Pubmed, doi:10.1158/1078-0432.CCR-08-0358.
PMID
18698045
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
14
Issue
16
Publish Date
2008
Start Page
5255
End Page
5259
DOI
10.1158/1078-0432.CCR-08-0358

Concurrent chemotherapy and re-irradiation for locoregionally recurrent head and neck cancer.

Recurrent and second primary tumors arising within a previously radiated head and neck volume represent a difficult clinical scenario to manage. For patients who have resectable disease, surgery is the standard treatment. Chemotherapy is the standard for patients with unresectable or metastatic disease but offers no chance for cure. Re-irradiation (RRT) with concurrent chemotherapy is a potentially curative treatment option. In this article, we will review the basis for current chemoradiotherapy (CRT) regimens used in previously radiated patients, focusing on outcome and toxicity. Additionally, we will review radiotherapy techniques used in this setting and highlight the differences between definitive radiotherapy and RRT. Controversies, such as the utility of chemotherapy and RRT following surgical salvage, will be addressed. Finally, we will review investigations seeking to improve the therapeutic outcomes of patients treated with chemotherapy and RRT.

Authors
Salama, JK; Vokes, EE
MLA Citation
Salama, Joseph K., and Everett E. Vokes. “Concurrent chemotherapy and re-irradiation for locoregionally recurrent head and neck cancer..” Semin Oncol, vol. 35, no. 3, June 2008, pp. 251–61. Pubmed, doi:10.1053/j.seminoncol.2008.03.010.
PMID
18544440
Source
pubmed
Published In
Seminars in Oncology
Volume
35
Issue
3
Publish Date
2008
Start Page
251
End Page
261
DOI
10.1053/j.seminoncol.2008.03.010

Association between bone marrow dosimetric parameters and acute hematologic toxicity in anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy.

PURPOSE: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V(10) and PBM-V(20)) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. METHODS AND MATERIALS: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. RESULTS: Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V(5), V(10), V(15), and V(20) were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V(10), V(15), and V(20) (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). CONCLUSION: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.

Authors
Mell, LK; Schomas, DA; Salama, JK; Devisetty, K; Aydogan, B; Miller, RC; Jani, AB; Kindler, HL; Mundt, AJ; Roeske, JC; Chmura, SJ
MLA Citation
Mell, Loren K., et al. “Association between bone marrow dosimetric parameters and acute hematologic toxicity in anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy..” Int J Radiat Oncol Biol Phys, vol. 70, no. 5, Apr. 2008, pp. 1431–37. Pubmed, doi:10.1016/j.ijrobp.2007.08.074.
PMID
17996390
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
70
Issue
5
Publish Date
2008
Start Page
1431
End Page
1437
DOI
10.1016/j.ijrobp.2007.08.074

In reply

Authors
Salama, JK; Chmura, SJ
MLA Citation
Salama, J. K., and S. J. Chmura. “In reply.” Journal of Clinical Oncology, vol. 26, no. 4, Feb. 2008, pp. 688–89. Scopus, doi:10.1200/JCO.2007.15.0714.
Source
scopus
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
26
Issue
4
Publish Date
2008
Start Page
688
End Page
689
DOI
10.1200/JCO.2007.15.0714

Does Cetuximab Improve Control of Advanced Head and Neck Cancer? A Second Look at the Randomized Trial by Bonner, et al.

Authors
Mell, LK; Dignam, JJ; Salama, JK; Haraf, DJ; Vokes, EE; Weichselbaum, RR
MLA Citation
Mell, L. K., et al. “Does Cetuximab Improve Control of Advanced Head and Neck Cancer? A Second Look at the Randomized Trial by Bonner, et al..” International Journal of Radiation Oncology*Biology*Physics, vol. 69, no. 3, Elsevier BV, 2007, pp. S419–S419. Crossref, doi:10.1016/j.ijrobp.2007.07.1562.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
69
Issue
3
Publish Date
2007
Start Page
S419
End Page
S419
DOI
10.1016/j.ijrobp.2007.07.1562

Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience.

PURPOSE: To report a multicenter experience treating anal canal cancer patients with concurrent chemotherapy and intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: From October 2000 to June 2006, 53 patients were treated with concurrent chemotherapy and IMRT for anal squamous cell carcinoma at three tertiary-care academic medical centers. Sixty-two percent were T1-2, and 67% were N0; eight patients were HIV positive. Forty-eight patients received fluorouracil (FU)/mitomycin, one received FU/cisplatin, and four received FU alone. All patients underwent computed tomography-based treatment planning with pelvic regions and inguinal nodes receiving a median of 45 Gy. Primary sites and involved nodes were boosted to a median dose of 51.5 Gy. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. All late toxicity was scored using Radiation Therapy Oncology Group criteria. RESULTS: Median follow-up was 14.5 months (range, 5.2 to 102.8 months). Acute grade 3+ toxicity included 15.1% GI and 37.7% dermatologic toxicity; all acute grade 4 toxicities were hematologic; and acute grade 4 leukopenia and neutropenia occurred in 30.2% and 34.0% of patients, respectively. Treatment breaks occurred in 41.5% of patients, lasting a median of 4 days. Forty-nine patients (92.5%) had a complete response, one patient had a partial response, and three had stable disease. All HIV-positive patients achieved a complete response. Eighteen-month colostomy-free survival, overall survival, freedom from local failure, and freedom from distant failure were 83.7%, 93.4%, 83.9%, and 92.9%, respectively. CONCLUSION: Preliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.

Authors
Salama, JK; Mell, LK; Schomas, DA; Miller, RC; Devisetty, K; Jani, AB; Mundt, AJ; Roeske, JC; Liauw, SL; Chmura, SJ
MLA Citation
Salama, Joseph K., et al. “Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience..” J Clin Oncol, vol. 25, no. 29, Oct. 2007, pp. 4581–86. Pubmed, doi:10.1200/JCO.2007.12.0170.
PMID
17925552
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
29
Publish Date
2007
Start Page
4581
End Page
4586
DOI
10.1200/JCO.2007.12.0170

Chemoradiotherapy for locally advanced head and neck cancer.

Authors
Salama, JK; Seiwert, TY; Vokes, EE
MLA Citation
Salama, Joseph K., et al. “Chemoradiotherapy for locally advanced head and neck cancer..” J Clin Oncol, vol. 25, no. 26, Sept. 2007, pp. 4118–26. Pubmed, doi:10.1200/JCO.2007.12.2697.
PMID
17827462
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
26
Publish Date
2007
Start Page
4118
End Page
4126
DOI
10.1200/JCO.2007.12.2697

Chemotherapy and high dose radiotherapy followed by resection for locally advanced nonsmall cell lung cancers.

OBJECTIVES: For locally advanced but technically operable nonsmall cell lung cancer (NSCLC), neoadjuvant chemoradiotherapy is frequently used. Ideal radiotherapy dose in this context is unclear. MATERIALS AND METHODS: Twenty-six NSCLC patients with N2 disease were retrospectively reviewed. All received preoperative concurrent platinum-based chemoradiotherapy. Gross tumor volumes received a median of 58 Gy (range, 50-60 Gy). RESULTS: Two patients experienced major complications and died, resulting in a postoperative mortality rate of 7.7%. Three patients (11.5%) had minor complications. Pathologic specimens revealed downstaging in 76.9% of patients. The pathologic complete response (CR) rate was 34.6%. Downstaging of nodes was observed in 20 of 26 patients. With a median follow-up of 18.3 months, the 1- and 3-year actuarial survival rates were 80.2% and 45.7%, respectively. The 1- and 3-year actuarial disease-free survival (DFS) rates were 76.9% and 37.3%, respectively. Patients experiencing mediastinal downstaging had better DFS rates, relative to patients that did not (18-month DFS = 79.2% vs. 0%; P = 0.0001). Differences in RT dose (50-60 Gy) and types of chemotherapeutic regimens did not significantly impact pathologic downstaging rates, CR rates, DFS, or survival. DISCUSSION: Neoadjuvant chemotherapy with high-dose concurrent RT is well tolerated and results in favorable outcomes.

Authors
Shaikh, AY; Haraf, DJ; Salama, JK; Salgia, R; Hoffman, PC; Ferguson, MK; Connell, PP
MLA Citation
Shaikh, Arif Y., et al. “Chemotherapy and high dose radiotherapy followed by resection for locally advanced nonsmall cell lung cancers..” Am J Clin Oncol, vol. 30, no. 3, June 2007, pp. 258–63. Pubmed, doi:10.1097/01.coc.0000258109.83083.78.
PMID
17551302
Source
pubmed
Published In
American Journal of Clinical Oncology
Volume
30
Issue
3
Publish Date
2007
Start Page
258
End Page
263
DOI
10.1097/01.coc.0000258109.83083.78

The chemoradiation paradigm in head and neck cancer.

In this article, we use the example of head and neck cancer to show how concurrent chemoradiotherapy is used to treat a cancer where locoregional control is central for treatment success. The advent of concurrent chemoradiation has significantly contributed to the curability of head and neck cancer, including locoregionally advanced disease. Preserving organ function and reducing toxic effects are increasingly the focus of clinical trials. We review the available chemoradiotherapy platforms used for head and neck cancer, with initial discussions focused on single-agent cytotoxic-based regimens. We then assess the literature on multiagent-based regimens and include a discussion of the integration of novel agents, such as EGFR inhibitors, and antiangiogenic drugs into treatment platforms. Although single-agent cisplatin-based chemoradiotherapy is still widely used as a standard therapy, we propose that evidence increasingly shows that multiagent-based chemoradiotherapy, and EGFR-inhibitor-based treatments, offer distinct advantages. We provide guidance for clinicians based on current clinical trial evidence on how to choose appropriate treatment platforms for their patients.

Authors
Seiwert, TY; Salama, JK; Vokes, EE
MLA Citation
Seiwert, Tanguy Y., et al. “The chemoradiation paradigm in head and neck cancer..” Nat Clin Pract Oncol, vol. 4, no. 3, Mar. 2007, pp. 156–71. Pubmed, doi:10.1038/ncponc0750.
PMID
17327856
Source
pubmed
Published In
Nat Clin Pract Oncol
Volume
4
Issue
3
Publish Date
2007
Start Page
156
End Page
171
DOI
10.1038/ncponc0750

The concurrent chemoradiation paradigm--general principles.

During the past 20 years, the advent of neoadjuvant, primary, and adjuvant concurrent chemoradiotherapy has improved cancer care dramatically. Significant contributions have been made by technological improvements in radiotherapy, as well as by the introduction of novel chemotherapy agents and dosing schedules. This article will review the rationale for the use of concurrent chemoradiotherapy for treating malignancies. The molecular basis and mechanisms of action of combining classic cytotoxic agents (e.g. platinum-containing drugs, taxanes, etc.) and novel agents (e.g. tirapazamine, EGFR inhibitors and other targeted agents) with radiotherapy will be examined. This article is part one of two articles. In the subsequent article, the general principles outlined here will be applied to head and neck cancer, in which the impact of concurrent chemoradiotherapy is particularly evident.

Authors
Seiwert, TY; Salama, JK; Vokes, EE
MLA Citation
Seiwert, Tanguy Y., et al. “The concurrent chemoradiation paradigm--general principles..” Nat Clin Pract Oncol, vol. 4, no. 2, Feb. 2007, pp. 86–100. Pubmed, doi:10.1038/ncponc0714.
PMID
17259930
Source
pubmed
Published In
Nat Clin Pract Oncol
Volume
4
Issue
2
Publish Date
2007
Start Page
86
End Page
100
DOI
10.1038/ncponc0714

Induced sensitization of tumor stroma leads to eradication of established cancer by T cells.

Targeting cancer cells, as well as the nonmalignant stromal cells cross-presenting the tumor antigen (Ag), can lead to the complete destruction of well-established solid tumors by adoptively transferred Ag-specific cytotoxic T lymphocytes (CTLs). If, however, cancer cells express only low levels of the Ag, then stromal cells are not destroyed, and the tumor escapes as Ag loss variants. We show that treating well-established tumors expressing low levels of Ag with local irradiation or a chemotherapeutic drug causes sufficient release of Ag to sensitize stromal cells for destruction by CTLs. This was shown directly using high affinity T cell receptor tetramers for visualizing the transient appearance of tumor-specific peptide-MHC complexes on stromal cells. Maximum loading of tumor stroma with cancer Ag occurred 2 d after treatment and coincided with the optimal time for T cell transfer. Under these conditions, tumor rejection was complete. These findings may set the stage for developing rational clinical protocols for combining irradiation or chemotherapy with CTL therapy.

Authors
Zhang, B; Bowerman, NA; Salama, JK; Schmidt, H; Spiotto, MT; Schietinger, A; Yu, P; Fu, Y-X; Weichselbaum, RR; Rowley, DA; Kranz, DM; Schreiber, H
MLA Citation
Zhang, Bin, et al. “Induced sensitization of tumor stroma leads to eradication of established cancer by T cells..” J Exp Med, vol. 204, no. 1, Jan. 2007, pp. 49–55. Pubmed, doi:10.1084/jem.20062056.
PMID
17210731
Source
pubmed
Published In
The Journal of Experimental Medicine
Volume
204
Issue
1
Publish Date
2007
Start Page
49
End Page
55
DOI
10.1084/jem.20062056

Induced sensitization of tumor stroma leads to eradication of established cancer by T cells

Authors
Zhang, B; Bowerman, NA; Salama, JK; Schmidt, H; Spiotto, MT; Schietinger, A; Yu, P; Fu, Y-X; Weichselbaum, RR; Rowley, DA; Kranz, DM; Schreiber, H
MLA Citation
Zhang, Bin, et al. “Induced sensitization of tumor stroma leads to eradication of established cancer by T cells.” Journal of Experimental Medicine, vol. 204, no. 1, ROCKEFELLER UNIV PRESS, Jan. 2007, pp. 49–55. Wos, doi:10.1084/jem.20062056.
Source
wos
Published In
The Journal of Experimental Medicine
Volume
204
Issue
1
Publish Date
2007
Start Page
49
End Page
55
DOI
10.1084/jem.20062056

SU‐FF‐T‐11: A Dosimetric Study of the Effect of Respiratory Motion On Whole Breast Radiation Therapy

Purpose: Study the effect of respiratory motion on whole breast radiotherapy for three treatment planning techniques: conventional wedged technique (CWT), segment IMRT (SIMRT) and beamlet IMRT (BIMRT). Investigate the relationship between the dosimetric coverage difference introduced by respiration and breast motion. Method and Materials: Eight patients with early stage breast cancer underwent free breathing (FB) CT simulation for whole breast radiotherapy. Two additional CT scans were obtained at the end of inspiration (EI) and end of expiration (EE). The FB scan was used to develop three plans using CWT, SIMRT and BIMRT. Each plan was copied and applied to EI and EE scans. The dose volume histograms were compared and statistical methods were used to investigate the relationship between dosimetric coverage and breast motion. Results: Medial and lateral markers of EI scans moved an average of 8 mm and 3mm, respectively. Both medial and lateral radiopaque markers of EE scans moved an average of 2 mm. For CWT and SIMRT, the percentage of CTV volume receiving 95% of the prescription dose V95%remained almost constant. BIMRT was relatively sensitive to respiratory motion. The average difference comparing FB and EI for the eight patients was 4.3% (V95%) and 7.4% (V100%). FB dose coverage remained almost the same as EE. A linear relationship with marker motion was found in the V100%difference between FB and EI. Conclusion: This study shows CWT and SIMRT are less sensitive to respiratory motion than the BIMRT. A linear model was found to relate the dosimetric coverage difference introduced by respiration with the breast motion. With this model, the dosimetric coverage difference could be evaluated during CT simulation. Based on the studies, we recommend BIMRT is not used for whole breast radiotherapy unless respiration control is used and SIMRT could be used without control. © 2007, American Association of Physicists in Medicine. All rights reserved.

Authors
Cao, J; Roeske, J; Schumra, S; Salama, J; Shoushtari, A; Boyer, A; Martel, M
MLA Citation
Cao, J., et al. “SU‐FF‐T‐11: A Dosimetric Study of the Effect of Respiratory Motion On Whole Breast Radiation Therapy.” Medical Physics, vol. 34, no. 6, Jan. 2007. Scopus, doi:10.1118/1.2760656.
Source
scopus
Published In
Medical Physics
Volume
34
Issue
6
Publish Date
2007
Start Page
2403
DOI
10.1118/1.2760656

2138

Authors
Devisetty, K; Mell, LK; Salama, JK; Jani, AB; Mundt, AJ; Roeske, J; Aydogan, B; Chmura, SJ
MLA Citation
Devisetty, K., et al. “2138.” International Journal of Radiation Oncology*Biology*Physics, vol. 66, no. 3, Elsevier BV, 2006, pp. S287–88. Crossref, doi:10.1016/j.ijrobp.2006.07.542.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S287
End Page
S288
DOI
10.1016/j.ijrobp.2006.07.542

2121

Authors
Mell, LK; Salama, JK; Roeske, JC; Devisetty, K; Jani, AB; Mundt, AJ; Chmura, SJ
MLA Citation
Mell, L. K., et al. “2121.” International Journal of Radiation Oncology*Biology*Physics, vol. 66, no. 3, Elsevier BV, 2006, pp. S277–78. Crossref, doi:10.1016/j.ijrobp.2006.07.525.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S277
End Page
S278
DOI
10.1016/j.ijrobp.2006.07.525

2114

Authors
Salama, JK; Mell, LK; Devisetty, K; Jani, AB; Mundt, AJ; Roeske, JC; Chmura, SJ
MLA Citation
Salama, J. K., et al. “2114.” International Journal of Radiation Oncology*Biology*Physics, vol. 66, no. 3, Elsevier BV, 2006, pp. S273–74. Crossref, doi:10.1016/j.ijrobp.2006.07.518.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S273
End Page
S274
DOI
10.1016/j.ijrobp.2006.07.518

24

Authors
Knab, BR; Salama, JK; Stenson, KM; Cohen, EE; List, MA; Witt, ME; Dekker, A; Vokes, EE; Haraf, DJ
MLA Citation
Knab, B. R., et al. “24.” International Journal of Radiation Oncology*Biology*Physics, vol. 66, no. 3, Elsevier BV, 2006, pp. S14–S14. Crossref, doi:10.1016/j.ijrobp.2006.07.048.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S14
End Page
S14
DOI
10.1016/j.ijrobp.2006.07.048

2425

Authors
Kochanski, JD; Salama, JK; Mell, LK; Stenson, K; Cohen, E; List, M; Witt, M; Dekker, A; Vokes, E; Haraf, DJ
MLA Citation
Kochanski, J. D., et al. “2425.” International Journal of Radiation Oncology*Biology*Physics, vol. 66, no. 3, Elsevier BV, 2006, pp. S446–S446. Crossref, doi:10.1016/j.ijrobp.2006.07.835.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S446
End Page
S446
DOI
10.1016/j.ijrobp.2006.07.835

2564

Authors
Weichselbaum, RR; Salama, JK; Mehta, N; Yenice, KM; Martel, MK; Connell, PP; Haraf, DJ; Chmura, SJ; Hellman, S
MLA Citation
Weichselbaum, R. R., et al. “2564.” International Journal of Radiation Oncology*Biology*Physics, vol. 66, no. 3, Elsevier BV, 2006, pp. S523–S523. Crossref, doi:10.1016/j.ijrobp.2006.07.977.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S523
End Page
S523
DOI
10.1016/j.ijrobp.2006.07.977

Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies.

PURPOSE: The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. METHODS AND MATERIALS: Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aortic lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. RESULTS: The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. CONCLUSIONS: Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising.

Authors
Salama, JK; Mundt, AJ; Roeske, J; Mehta, N
MLA Citation
Salama, Joseph K., et al. “Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies..” Int J Radiat Oncol Biol Phys, vol. 65, no. 4, July 2006, pp. 1170–76. Pubmed, doi:10.1016/j.ijrobp.2006.02.041.
PMID
16730136
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
65
Issue
4
Publish Date
2006
Start Page
1170
End Page
1176
DOI
10.1016/j.ijrobp.2006.02.041

Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma.

PURPOSE: To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation. METHODS AND MATERIALS: Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n=14), cisplatin plus FHX (n=23), paclitaxel plus FHX (n=42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n=26), and irinotecan plus FHX (n=10). RESULTS: The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%, respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage. CONCLUSION: For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for long-term survival. Owing to the substantial toxicity and lack of an optimal regimen, reirradiation of recurrent head-and-neck cancer should be limited to clinical trials.

Authors
Salama, JK; Vokes, EE; Chmura, SJ; Milano, MT; Kao, J; Stenson, KM; Witt, ME; Haraf, DJ
MLA Citation
Salama, Joseph K., et al. “Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma..” Int J Radiat Oncol Biol Phys, vol. 64, no. 2, Feb. 2006, pp. 382–91. Pubmed, doi:10.1016/j.ijrobp.2005.07.005.
PMID
16213104
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
64
Issue
2
Publish Date
2006
Start Page
382
End Page
391
DOI
10.1016/j.ijrobp.2005.07.005

Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy.

PURPOSE: We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX(2)) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX(2) in a subset of patients previously irradiated to the head and neck. METHODS AND MATERIALS: Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX(2). Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). RESULTS: The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. CONCLUSION: Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival.

Authors
Milano, MT; Vokes, EE; Salama, JK; Stenson, KM; Kao, J; Witt, M-E; Mittal, BB; Argiris, A; Weichselbaum, RR; Haraf, DJ
MLA Citation
Milano, Michael T., et al. “Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy..” Int J Radiat Oncol Biol Phys, vol. 61, no. 4, Mar. 2005, pp. 1096–106. Pubmed, doi:10.1016/j.ijrobp.2004.08.029.
PMID
15752889
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
61
Issue
4
Publish Date
2005
Start Page
1096
End Page
1106
DOI
10.1016/j.ijrobp.2004.08.029

Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer.

PURPOSE: We sought to investigate CPT-11 as a promising agent to our established regimen of 5-fluorouracil (5-FU), hydroxyurea, and hyperfractionated radiation therapy. A phase I study was conducted to determine the maximum tolerated dose and dose-limiting toxicities of this regimen. PATIENTS AND METHODS: Eligible patients included patients with poor prognosis advanced head and neck cancer who required radiation therapy. All patients were treated on a 14-day cycle. Each patient received 5-FU (600 mg/m(2)/d), hydroxyurea (500 mg orally every 12 hours), radiation therapy twice daily (150 cGy each fraction), and CPT-11 at a starting dose of 5 mg/m(2)/d for 5 consecutive days followed by a 9-day break. CPT-11 was escalated in five mg/m(2)/d increments. Dose-limiting toxicity was defined as grade 4 hematologic toxicity, persistent grade 4 dermatitis and mucositis, grade 4 diarrhea despite maximal pharmacologic intervention, and inability to receive full-dose chemotherapy with the next cycle of treatment. Fourteen patients were treated at maximum tolerated dose to verify the recommended phase II dose. RESULTS: Between August 1998 and August 2001, 31 patients with advanced and/or recurrent head and neck cancer were enrolled. Cohorts of nine, four, three, and 14 patients were treated at 5-, 10-, 15-, and 10-mg/m(2)/d dose levels of CPT-11. The 5- and 10-mg/m(2)/d dose levels were well tolerated All three patients treated at 15 mg/m(2)/d experienced neutropenic dose-limiting toxicity during cycles 1-2. DISCUSSION: The maximum tolerated dose and recommended phase II dose of CPT-11 with hyperfractionated radiation therapy is 10 mg/m(2)/d.

Authors
Salama, JK; Haraf, DJ; Stenson, K; Milano, MT; Witt, ME; Vokes, EE
MLA Citation
Salama, Joseph K., et al. “Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer..” Cancer J, vol. 11, no. 2, Mar. 2005, pp. 140–46.
PMID
15969989
Source
pubmed
Published In
Cancer Journal (Sudbury, Mass.)
Volume
11
Issue
2
Publish Date
2005
Start Page
140
End Page
146

Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?

BACKGROUND: There are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor-free axillary lymph nodes on disease-free survival (DFS) in two distinct patient populations. METHODS: Eight hundred thirty-three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast-conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1-3 lymph nodes examined, Group 2 had 4-9 lymph nodes examined, Group 3 had 10-20 lymph nodes examined, and Group 4 had >20 lymph nodes examined. RESULTS: In the mastectomy cohort, with a median follow-up of 153 months, the 10-year DFS rate was 70%, 65%, 79%, and 81% for Groups 1-4, respectively. On multivariate analysis, pathologic tumor size (P<0.001) and the number of lymph nodes examined (P=0.010) were significant predictors for long-term DFS. In the breast-conservation cohort, with a median follow-up of 53 months, the 5-year DFS rate was 90%, 91%, 92%, and 95% for Groups 1-4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P=0.003) and tumor size (P=0.035). CONCLUSIONS: The recovery of <10 lymph nodes in lymph node-negative patients who underwent mastectomy resulted in a 10-15% decreased long-term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast-conservation therapy, which included radiation.

Authors
Salama, JK; Heimann, R; Lin, F; Mehta, N; Chmura, SJ; Singh, R; Kao, J
MLA Citation
Salama, Joseph K., et al. “Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?.” Cancer, vol. 103, no. 4, Feb. 2005, pp. 664–71. Pubmed, doi:10.1002/cncr.20830.
PMID
15641038
Source
pubmed
Published In
Cancer
Volume
103
Issue
4
Publish Date
2005
Start Page
664
End Page
671
DOI
10.1002/cncr.20830

Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer: Toxicity and outcome results.

5561 Background: At University of Chicago, concomitant chemoRT for advanced and recurrent head and neck cancer has been studied for 2 decades. We investigated the addition of CPT-11 as a promising new agent to our established regimen of 5-FU, hydroxyurea (HU), and hyperfractionated RT (HF2X). The goal was to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of this regimen. Time to progression, patterns of failure, and survival were secondary endpoints. METHODS: Between 8/98 and 8/01, 31 pts with advanced and recurrent H&N cancer were enrolled. Previously untreated pts were eligible if unressectable or had an expected 2 year survival <20%. Pts with metastatic disease were included if local radiotherapy to the H&N was required. 19 previously radiated pts were included. The median prior RT dose was 66.4 Gy (range: 45-88.4 Gy). The starting dose of CPT-11 was 5 mg/m(2)/d delivered with continuous infusion 5-FU (600 mg/m(2)/d), HU (500 mg PO q 12 hours) and BID RT (1.5 Gy/fraction). All pts were treated on a 14 d cycle with 5 consecutive days of therapy and a 9 day break. Subsequent cohorts had CPT-11 escalated by 5 mg/m(2)/d. Subsequently, 14 pts were treated at the MTD. RESULTS: CPT-11 was well tolerated at the 5 mg/m(2)/d and 10 mg/m(2)/d dose levels. 3/3 pts treated at the 15 mg/m(2)/d level, experienced neutropenic DLT during cycles 1-2. 8/18 (44%) evaluable pts had a response; 5 (28%) had a CR, 3 (17%) had a PR, 5 had stable disease (28%) and 5 pts progressed. At a median f/u of 24 mos for surviving pts, (range, 16.5-51), 4 pts (13%) are alive and NED. 2 yr overall survival (OS) and disease free survival (DFS) was 31.3% and 24.4%. Re-irradiated pts had a median survival of 9.5 mos (range: 0.7-50.5) and a 2 yr OS of 24.5%. 2 yr DFS of squamous histology re-irradiation pts was 23%. CONCLUSIONS: The MTD and recommended phase II dose of CPT-11/ HF2X was 10 mg/m(2)/d. Neutropenia was dose limiting. Response rates were reasonable. Further investigation of this regimen may be worth additional study. Re-irradiation with concurrent chemotherapy resulted in the survival of a significant fraction of pts. No significant financial relationships to disclose.

Authors
Salama, JK; Haraf, DJ; Stenson, K; Vokes, EE
MLA Citation
Salama, J. K., et al. “Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer: Toxicity and outcome results..” J Clin Oncol, vol. 22, no. 14_suppl, July 2004.
PMID
28014027
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
14_suppl
Publish Date
2004
Start Page
5561

Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer: Toxicity and outcome results.

Authors
Salama, JK; Haraf, DJ; Stenson, K; Vokes, EE
MLA Citation
Salama, J. K., et al. “Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer: Toxicity and outcome results..” Journal of Clinical Oncology, vol. 22, no. 14, AMER SOC CLINICAL ONCOLOGY, 2004, pp. 503S-503S.
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
22
Issue
14
Publish Date
2004
Start Page
503S
End Page
503S

Intensity-modulated radiation therapy in gynecologic malignancies.

Radiation therapy occupies an important role in the treatment of gynecologic malignancies. Unfortunately, traditional approaches result in the irradiation of large volumes of normal tissues exposing patients to many toxicities and precluding dose escalation in select patients. A novel approach to the planning and delivery of radiation therapy, known as intensity-modulated radiation therapy (IMRT), has been introduced. Unlike conventional approaches, IMRT conforms the prescription dose to the shape of the target in three dimensions, thus sparing the surrounding normal tissues. Multiple studies have demonstrated the clear superiority of IMRT planning in these patients in terms of normal tissue sparing. Promising clinical results have also been published, suggesting that IMRT reduces the incidence of acute and chronic toxicity in these women. Ongoing studies are focusing on tumor control and patient outcome. Although further work is needed, these results suggest that IMRT may represent a major advancement in the planning and delivery of radiation therapy in patients with gynecologic malignancies.

Authors
Salama, JK; Roeske, JC; Mehta, N; Mundt, AJ
MLA Citation
Salama, Joseph K., et al. “Intensity-modulated radiation therapy in gynecologic malignancies..” Curr Treat Options Oncol, vol. 5, no. 2, Apr. 2004, pp. 97–108.
PMID
14990204
Source
pubmed
Published In
Current Treatment Options in Oncology
Volume
5
Issue
2
Publish Date
2004
Start Page
97
End Page
108

Evaluation of patients after extraperitoneal lymph node dissection and subsequent radiotherapy for cervical cancer.

OBJECTIVE: The presence of nodal metastases is the most important prognostic factor in cervical cancer. To adjust our therapy based on the true extent of the patient's disease, we performed an extraperitoneal lymph node dissection (EPLND) in all patients with cervical cancer prior to radiotherapy (RT) or radical hysterectomy. METHODS: Thirty-three patients with carcinoma of the cervix underwent EPLND. The value of this procedure as a diagnostic tool for monitoring the extension of the disease was determined. Additionally, EPLND/RT-associated treatment complications were monitored. RESULTS: The combined treatment approach of EPLND with RT or chemotherapy/RT was without major complications. Nineteen patients showed a temperature elevation, but only one patient had a fever of greater than 39.0 degrees C. Fourteen (48.3%) of 29 patients experienced some degree of proctitis or diarrhea and 3 (10.3%) experienced cystitis during the course of RT. No grade 3 or 4 acute or late genitourinary or gastrointestinal toxicities were noted. EPLND changed the clinical management for 6 patients from a radical hysterectomy to RT and for 7 patients from standard-field RT to extended-field RT. Without EPLND these 7 patients would have received RT with standard pelvic fields that would not have treated involved lymph node areas at high risk for subsequent failure. CONCLUSION: Thirteen (44.8%) of 29 patients received a different treatment than would otherwise have been administered with standard treatment planning. Therefore, we suggest that EPLND should be performed in all patients with cervical cancer prior to radical surgery or RT.

Authors
Hasenburg, A; Salama, JK; Van, TJ; Amosson, C; Chiu, JK; Kieback, DG
MLA Citation
Hasenburg, Annette, et al. “Evaluation of patients after extraperitoneal lymph node dissection and subsequent radiotherapy for cervical cancer..” Gynecol Oncol, vol. 84, no. 2, Feb. 2002, pp. 321–26. Pubmed, doi:10.1006/gyno.2001.6528.
PMID
11812094
Source
pubmed
Published In
Gynecologic Oncology
Volume
84
Issue
2
Publish Date
2002
Start Page
321
End Page
326
DOI
10.1006/gyno.2001.6528

Phase I Study of Concomitant Chemoradiotherapy with Irinotecan, 5-FU, and Hydroxyurea fot Patients with Advanced and/or Recurrent Head and Neck Cancer

PURPOSE We sought to investigate CPT-11 as a promising agent to our established regimen of 5-fluorouracil (5-FU), hydroxyurea, and hyperfractionated radiation therapy. A phase I study was conducted to determine the maximum tolerated dose and dose-limiting toxicities of this regimen. PATIENTS AND METHODS Eligible patients included patients with poor prognosis advanced head and neck cancer who required radiation therapy. All patients were treated on a 14-day cycle. Each patient received 5-FU (600 mg/m2/d), hydroxyurea (500 mg orally every 12 hours), radiation therapy twice daily (150 cGy each fraction), and CPT-11 at a starting dose of 5 mg/m2/d for 5 consecutive days followed by a 9-day break. CPT-11 was escalated in five mg/m2/d increments. Dose-limiting toxicity was defined as grade 4 hematologie toxicity, persistent grade 4 dermatitis and mucositis, grade 4 diarrhea despite maximal pharmacologie intervention, and inability to receive full-dose chemotherapy with the next cycle of treatment. Fourteen patients were treated at maximum tolerated dose to verify the recommended phase II dose. RESULTS Between August 1998 and August 2001, 31 patients with advanced and/or recurrent head and neck cancer were enrolled. Cohorts of nine, four, three, and 14 patients were treated at 5-, 10-, 15-, and 10-mg/m2/d dose levels of CPT-11. The 5- and 10-mg/m2/d dose levels were well tolerated. All three patients treated at 15 mg/m2/d experienced neutropenic dose-limiting toxicity during cycles 1-2. DISCUSSION The maximum tolerated dose and recommended phase II dose of CPT-11 with hyperfractionated radiation therapy is 10 mg/m2/d. Copyright © 2005 Jones and Bartlett Publishers, Inc.

Authors
Salama, JK; Haraf, DJ; Stenson, K; Milano, MT; Witt, ME; Vokes, EE
MLA Citation
Salama, J. K., et al. “Phase I Study of Concomitant Chemoradiotherapy with Irinotecan, 5-FU, and Hydroxyurea fot Patients with Advanced and/or Recurrent Head and Neck Cancer.” Cancer Journal, vol. 11, no. 2, Dec. 1998, pp. 140–46.
Source
scopus
Published In
Cancer Journal (Sudbury, Mass.)
Volume
11
Issue
2
Publish Date
1998
Start Page
140
End Page
146

The morphology of the femur in developmental dysplasia of the hip.

We studied the morphometry of 35 femora from 31 female patients with developmental dysplasia of the hip (DDH) and another 15 from 15 age- and sex-matched control patients using CT and three-dimensional computer reconstruction models. According to the classification of Crowe et al 15 of the dysplastic hips were graded as class I (less than 50% subluxation), ten as class I/III (50% to 100% subluxation) and ten as class IV (more than 100% subluxation). The femora with DDH had 10 to 14 degrees more anteversion than the control group independent of the degree of subluxation of the hip. In even the most mildly dysplastic joints, the femur had a smaller and more anteverted canal than the normal control. With increased subluxation, additional abnormalities were observed in the size and position of the femoral head. Femora from dislocated joints had a short, anteverted neck associated with a smaller, narrower, and straighter canal than femora of classes I and II/III or the normal control group. We suggest that when total hip replacement is performed in the patient with DDH, the femoral prosthesis should be chosen on the basis of the severity of the subluxation and the degree of anteversion of each individual femur.

Authors
Sugano, N; Noble, PC; Kamaric, E; Salama, JK; Ochi, T; Tullos, HS
MLA Citation
Sugano, N., et al. “The morphology of the femur in developmental dysplasia of the hip..” J Bone Joint Surg Br, vol. 80, no. 4, July 1998, pp. 711–19.
PMID
9699842
Source
pubmed
Published In
The Journal of Bone and Joint Surgery. British Volume
Volume
80
Issue
4
Publish Date
1998
Start Page
711
End Page
719

TEM studies of dislocations in deformed melt-textured YBa2Cu30x superconductors

TEM studies have been conducted on melt-textured YBa2Cu3Ox, samples that were uniaxially and isostatically deformed at high temperatures and compared with those of undeformed samples. Dislocation pile-ups along [100] and [010] are found to be the common feature between undeformed samples with the best Jcand the uniaxially deformed samples, and are suggested to be responsible for enhanced pinning when the magnetic field (H) is applied parallel to the a-b plane. Dislocation loops, tangles, and arrays are also observed, and are considered to contribute to pinning in field orientations other than H∥a-b. In addition to these dislocations, (301) type partial dislocations are found to be present in isostatically deformed samples. The strain field around these dislocations is considered to be an additional source of pinning in the intermediate field orientations. © 1993, Materials Research Society. All rights reserved.

Authors
Mironova, M; Selvamanickam, V; Lee, DF; Salama, K
MLA Citation
Mironova, M., et al. “TEM studies of dislocations in deformed melt-textured YBa2Cu30x superconductors.” Journal of Materials Research, vol. 8, no. 11, Jan. 1993, pp. 2767–73. Scopus, doi:10.1557/JMR.1993.2767.
Source
scopus
Published In
Journal of Materials Research
Volume
8
Issue
11
Publish Date
1993
Start Page
2767
End Page
2773
DOI
10.1557/JMR.1993.2767

Hippocampal dose from stereotactic radiosurgery for 4 to 10 brain metastases: Risk factors, feasibility of dose reduction via re-optimization, and patient outcomes.

This study aimed to report hippocampal dose from single-fraction stereotactic radiosurgery (SRS) for 4 to 10 brain metastases and determine feasibility of hippocampal-sparing SRS. Patients with 4 to 10 brain metastases receiving single-isocenter, multi-target single-fraction SRS were identified. Hippocampi were contoured using the Radiation Therapy Oncology Group (RTOG) 0933 atlas. RTOG 0933 dose constraints were converted to a biologically effective dose using an alpha/beta of 2 (D100 421 cGy, Dmax 665 cGy). Number of metastases, total target volume, prescribed dose, and distance of nearest metastasis (dmin) were analyzed as risk factors for exceeding hippocampal constraints. If hippocampi exceeded constraints, the SRS plan was re-optimized. Key dosimetric parameters were compared between original and re-optimized plans. To determine if a single target can exceed constraints, all targets but the closest metastasis were removed from the plan, and dosimetry was compared. Forty plans were identified. Fifteen hippocampi (19%) exceeded constraints in 12 SRS plans. Hippocampal sparing was achieved in 10 of 12 replanned cases (83%). Risk factors associated with exceeding hippocampal constraints were decreasing dmin (24.0 vs 8.0 mm, p = 0.002; odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04 to 1.26) and total target volume (5.46 cm3vs 1.98 cm3, p = 0.03; OR 1.14, 95% CI 1.00 to 1.32). There was no difference in exceeding constraints for 4 to 5 vs 6 to 10 metastases (27% vs 21%, p = 0.409) or prescribed dose (18 Gy, p = 0.58). For re-optimized plans, there were no significant differences in planning target volume (PTV) coverage (99.6% vs 99.0%, p = 0.17) or conformality index (1.47 vs 1.4, p = 0.78). Six (50%) plans exceeded constraints with a single target. A substantial minority of hippocampi receive high radiation dose from SRS for 4 to 10 brain metastases. Decreasing distance of the closest metastasis and total target volume are associated with exceeding hippocampal constraints. Re-optimizing these plans yielded hippocampal-sparing SRS plans with acceptable dosimetry. Prospective evaluation of the impact of hippocampal dose from SRS on neurocognition merits consideration.

Authors
Birer, SR; Olson, AC; Adamson, J; Hood, R; Susen, M; Kim, G; Salama, JK; Kirkpatrick, JP
MLA Citation
Birer, Samuel R., et al. “Hippocampal dose from stereotactic radiosurgery for 4 to 10 brain metastases: Risk factors, feasibility of dose reduction via re-optimization, and patient outcomes..” Med Dosim, vol. 42, no. 4, pp. 310–16. Pubmed, doi:10.1016/j.meddos.2017.06.007.
PMID
28760560
Source
pubmed
Published In
Med Dosim
Volume
42
Issue
4
Start Page
310
End Page
316
DOI
10.1016/j.meddos.2017.06.007
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