David Brizel

Overview:

Head and neck cancer has constituted both my principal clinical and research foci since I came to Duke University in 1987. I designed and led a single institution phase 3 randomized clinical trial, initiated in 1989, which was one of the first in the world to demonstrate that radiotherapy and concurrent chemotherapy (CRT) was more efficacious than radiotherapy alone (RT) for treating locally advanced head and neck cancer. CRT has since been established as the non-surgical standard of care for locally advanced head and neck cancer. Reduction of treatment-induced toxicity has also been a major interest of mine because more intensive therapeutic regimens improve efficacy but also increase morbidity. I was the principal investigator of the pivotal multinational randomized trial of amifostine in head and neck cancer, which established proof of principle for pharmacologic radioprotection and led to FDA approval of this drug for protection against radiation induced xerostomia in the treatment of head and neck cancer in 1999. I have also investigated role of recombinant human keratinocyte growth factor KGF in the amelioration of mucositis in both preclinical and clinical settings.
I have an ongoing commitment to the study of in situ tumor physiology and biology. I was one of the initial investigators to initiate direct measurement of tumor oxygenation in humans on a systematic basis. This work revealed a prognostic relationship between tumor hypoxia and local-regional failure and survival in head and neck. Parallel studies of tumor oxygenation in soft tissue sarcomas resulted in the first published literature to demonstrate that hypoxia at a primary tumor site was associated with a significant increase in the risk of subsequent distant metastatic recurrence after completion of treatment. We have also demonstrated that elevated lactate concentrations in head and neck cancer primary tumors is associated with an increased risk of metastatic failure in patients undergoing primary surgical therapy for head and neck cancer.
These interests and accomplishments provide the foundation for my present efforts, which are devoted to the development of functional metabolic imaging, both MRI and PET. We are using imaging to characterize the inherent, non-treatment induced variability of several physiologic and metabolic parameters in both tumors and normal tissues and to measure treatment induced changes in them. The long- term intent is to improve our abilities to predict treatment outcome, to better understand the relationships between physical dose delivery and the risk of toxicity, and to choose more customized treatment strategies for our patients that will increase the chances of cure and decrease the risks of serious side effects



Positions:

Leonard Prosnitz Distinguished Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Professor in Head and Neck Surgery and Communication Sciences

Head and Neck Surgery & Communication Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1983

Northwestern University

Grants:

BMX-001 as a Radio-Protector in Head and Neck Cancer Therapy Phase I and Phase II

Administered By
Radiation Oncology
Awarded By
BioMimetix Pharmaceutical, Inc.
Role
Principal Investigator
Start Date
End Date

Hyperglycemia and Oxygen Breathing in Head & Neck Cancer

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Heat & Radiation Effects On Tumor Microcirculation

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Effects Of Heat And Radiation On Tumor

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Publications:

A systematic review on sinonasal mixed adenoneuroendocrine carcinoma.

Authors
Issa, K; Smith, BD; Kaplan, SJ; Madden, J; Jang, DW; Zomorodi, A; Brizel, D; Abi Hachem, R
MLA Citation
Issa, Khalil, et al. “A systematic review on sinonasal mixed adenoneuroendocrine carcinoma.Int Forum Allergy Rhinol, vol. 11, no. 9, Sept. 2021, pp. 1391–94. Pubmed, doi:10.1002/alr.22811.
URI
https://scholars.duke.edu/individual/pub1483114
PMID
34013656
Source
pubmed
Published In
Int Forum Allergy Rhinol
Volume
11
Published Date
Start Page
1391
End Page
1394
DOI
10.1002/alr.22811

Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis.

BACKGROUND: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other. METHODS: We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies). FINDINGS: 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRTP) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRTP (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and ICTaxPF followed by CLRT (80%). INTERPRETATION: The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or ICTaxPF-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.
Authors
Petit, C; Lacas, B; Pignon, J-P; Le, QT; Grégoire, V; Grau, C; Hackshaw, A; Zackrisson, B; Parmar, MKB; Lee, J-W; Ghi, MG; Sanguineti, G; Temam, S; Cheugoua-Zanetsie, M; O'Sullivan, B; Posner, MR; Vokes, EE; Cruz Hernandez, JJ; Szutkowski, Z; Lartigau, E; Budach, V; Suwiński, R; Poulsen, M; Kumar, S; Ghosh Laskar, S; Mazeron, J-J; Jeremic, B; Simes, J; Zhong, L-P; Overgaard, J; Fortpied, C; Torres-Saavedra, P; Bourhis, J; Aupérin, A; Blanchard, P; MACH-NC and MARCH Collaborative Groups,
MLA Citation
Petit, Claire, et al. “Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis.Lancet Oncol, vol. 22, no. 5, May 2021, pp. 727–36. Pubmed, doi:10.1016/S1470-2045(21)00076-0.
URI
https://scholars.duke.edu/individual/pub1483637
PMID
33862002
Source
pubmed
Published In
Lancet Oncol
Volume
22
Published Date
Start Page
727
End Page
736
DOI
10.1016/S1470-2045(21)00076-0

Adjuvant Radiation Therapy for Clinical Stage III Melanoma in the Modern Therapeutic Era.

BACKGROUND: Adjuvant radiation therapy (RT) can decrease lymph node basin (LNB) recurrences in patients with clinically evident melanoma lymph node (LN) metastases following lymphadenectomy, but its role in the era of modern systemic therapies (ST), immune checkpoint or BRAF/MEK inhibitors, is unclear. PATIENTS AND METHODS: Patients at four institutions who underwent lymphadenectomy (1/1/2010-12/31/2019) for clinically evident melanoma LN metastases and received neoadjuvant and/or adjuvant ST with RT, or ST alone, but met indications for RT, were identified. Comparisons were made between ST alone and ST/RT groups. The primary outcome was 3-year cumulative incidence (CI) of LNB recurrence. Secondary outcomes included 3-year incidences of in-transit/distant recurrence and survival estimates. RESULTS: Of 98 patients, 76 received ST alone and 22 received ST/RT. Median follow-up time for patients alive at last follow-up was 44.6 months. The ST/RT group had fewer inguinal node metastases (ST 36.8% versus ST/RT 9.1%; P = 0.04), and more extranodal extension (ST 50% versus ST/RT 77.3%; P = 0.02) and positive lymphadenectomy margins (ST 2.6% versus ST/RT 13.6%; P = 0.04). The 3-year CI of LNB recurrences was lower for the ST/RT group compared with the ST group (13.9% versus 25.2%), but this reduction was not statistically significant (P = 0.36). Groups did not differ significantly in in-transit/distant recurrences (P = 0.24), disease-free survival (P = 0.14), or melanoma-specific survival (P = 0.20). CONCLUSIONS: In the era of modern ST, RT may still have value in reducing LNB recurrences in melanoma with clinical LN metastases. Further research should focus on whether select patient populations derive benefit from combination therapy, and optimizing indications for RT following neoadjuvant ST.
Authors
Straker, RJ; Song, Y; Sun, J; Shannon, AB; Cohen, LS; Muradova, E; Daou, H; Krause, K; Li, S; Frederick, DT; Rhodin, KE; Brizel, DM; Boland, GM; Beasley, GM; Wuthrick, EJ; Sondak, VK; Zager, JS; Lin, A; Lukens, JN; Karakousis, GC
MLA Citation
Straker, Richard J., et al. “Adjuvant Radiation Therapy for Clinical Stage III Melanoma in the Modern Therapeutic Era.Ann Surg Oncol, vol. 28, no. 7, July 2021, pp. 3512–21. Pubmed, doi:10.1245/s10434-020-09384-8.
URI
https://scholars.duke.edu/individual/pub1465205
PMID
33230747
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
28
Published Date
Start Page
3512
End Page
3521
DOI
10.1245/s10434-020-09384-8

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group.

BACKGROUND AND PURPOSE: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results. MATERIALS AND METHODS: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint. RESULTS: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005). CONCLUSION: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer.
Authors
Lacas, B; Carmel, A; Landais, C; Wong, SJ; Licitra, L; Tobias, JS; Burtness, B; Ghi, MG; Cohen, EEW; Grau, C; Wolf, G; Hitt, R; Corvò, R; Budach, V; Kumar, S; Laskar, SG; Mazeron, J-J; Zhong, L-P; Dobrowsky, W; Ghadjar, P; Fallai, C; Zakotnik, B; Sharma, A; Bensadoun, R-J; Ruo Redda, MG; Racadot, S; Fountzilas, G; Brizel, D; Rovea, P; Argiris, A; Nagy, ZT; Lee, J-W; Fortpied, C; Harris, J; Bourhis, J; Aupérin, A; Blanchard, P; Pignon, J-P; MACH-NC Collaborative Group,
MLA Citation
Lacas, Benjamin, et al. “Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group.Radiother Oncol, vol. 156, Mar. 2021, pp. 281–93. Pubmed, doi:10.1016/j.radonc.2021.01.013.
URI
https://scholars.duke.edu/individual/pub1474141
PMID
33515668
Source
pubmed
Published In
Radiother Oncol
Volume
156
Published Date
Start Page
281
End Page
293
DOI
10.1016/j.radonc.2021.01.013

Early 18F-FDG-PET Response During Radiation Therapy for HPV-Related Oropharyngeal Cancer May Predict Disease Recurrence.

PURPOSE: Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes. METHODS AND MATERIALS: Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of ∼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs). RESULTS: From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVmax (normalized to blood pool SUVmean) <6.7 or SUVmax (normalized to blood pool SUVmean) ≥6.7 with intratreatment SUV40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively. CONCLUSIONS: PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.
Authors
Mowery, YM; Vergalasova, I; Rushing, CN; Choudhury, KR; Niedzwiecki, D; Wu, Q; Yoo, DS; Das, S; Wong, TZ; Brizel, DM
MLA Citation
Mowery, Yvonne M., et al. “Early 18F-FDG-PET Response During Radiation Therapy for HPV-Related Oropharyngeal Cancer May Predict Disease Recurrence.Int J Radiat Oncol Biol Phys, vol. 108, no. 4, Nov. 2020, pp. 969–76. Pubmed, doi:10.1016/j.ijrobp.2020.08.029.
URI
https://scholars.duke.edu/individual/pub1456303
PMID
32800802
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
108
Published Date
Start Page
969
End Page
976
DOI
10.1016/j.ijrobp.2020.08.029