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 Surgery

Surgery, Head and Neck Surgery and Communication Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1983

Northwestern University

Grants:

Hyperthermia And Perfusion Effects In Cancer Therapy

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

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

Administered By
Radiation Oncology
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

Hyperthermia And Perfusion Effects In Cancer Therapy

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

Hyperthermia And Perfusion Effects In Cancer Therapy

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

Publications:

Dynamic contrast enhanced-MRI in head and neck cancer patients: variability of the precontrast longitudinal relaxation time (T10).

PURPOSE: Calculation of the precontrast longitudinal relaxation times (T10) is an integral part of the Tofts-based pharmacokinetic (PK) analysis of dynamic contrast enhanced-magnetic resonance images. The purpose of this study was to investigate the interpatient and over time variability of T10 in head and neck primary tumors and involved nodes and to determine the median T10 for primary and nodes (T10(p,n)). The authors also looked at the implication of using voxel-based T10 values versus region of interest (ROI)-based T10 on the calculated values for vascular permeability (K(trans)) and extracellular volume fraction (v(e)). METHODS: Twenty head and neck cancer patients receiving concurrent chemoradiation and molecularly targeted agents on a prospective trial comprised the study population. Voxel-based T10's were generated using a gradient echo sequence on a 1.5 T MR scanner using the variable flip angle method with two flip angles [J. A. Brookes et al., "Measurement of spin-lattice relaxation times with FLASH for dynamic MRI of the breast," Br. J. Radiol. 69, 206-214 (1996)]. The voxel-based T10, K(trans), and v(e) were calculated using iCAD's (Nashua, NH) software. The mean T10's in muscle and fat ROIs were calculated (T10(m,f)). To assess reliability of ROI drawing, T10(p,n) values from ROIs delineated by 2 users (A and B) were calculated as the average of the T10's for 14 patients. For a subset of three patients, the T10 variability from baseline to end of treatment was also investigated. The K(trans) and v(e) from primary and node ROIs were calculated using voxel-based T10 values and T10(p,n) and differences reported. RESULTS: The calculated T10 values for fat and muscle are within the range of values reported in literature for 1.5 T, i.e., T10(m) = 0.958 s and T10(f) = 0.303 s. The average over 14 patients of the T10's based on drawings by users A and B were T10(pA) = 0.804 s, T10(nA) = 0.760 s, T10(pB) = 0.849 s, and T10(nB) = 0.810 s. The absolute percentage difference between K(trans) and v(e) calculated with voxel-based T10 versus T10(p,n) ranged from 6% to 81% and from 2% to 24%, respectively. CONCLUSIONS: There is a certain amount of variability in the median T10 values between patients, but the differences are not significant. There were also no statistically significant differences between the T10 values for primary and nodes at baseline and the subsequent time points (p = 0.94 Friedman test). Voxel-based T10 calculations are essential when quantitative Tofts-based PK analysis in heterogeneous tumors is needed. In the absence of T10 mapping capability, when a relative, qualitative analysis is deemed sufficient, a value of T10(p,n) = 0.800 s can be used as an estimate for T10 for both the primary tumor and the affected nodes in head and neck cancers at all the time points considered.
Authors
Craciunescu, O; Brizel, D; Cleland, E; Yoo, D; Muradyan, N; Carroll, M; Barboriak, D; MacFall, J
MLA Citation
Craciunescu, Oana, et al. “Dynamic contrast enhanced-MRI in head and neck cancer patients: variability of the precontrast longitudinal relaxation time (T10)..” Med Phys, vol. 37, no. 6, June 2010, pp. 2683–92. Pubmed, doi:10.1118/1.3427487.
URI
https://scholars.duke.edu/individual/pub1254812
PMID
28512937
Source
pubmed
Published In
Medical Physics
Volume
37
Published Date
Start Page
2683
End Page
2692
DOI
10.1118/1.3427487

Reduced Uninsured Rates and Racial Disparities in Insurance Coverage for Head and Neck Cancer Patients After Medicaid Expansion

MLA Citation
Mowery, Y. M., et al. “Reduced Uninsured Rates and Racial Disparities in Insurance Coverage for Head and Neck Cancer Patients After Medicaid Expansion.” International Journal of Radiation Oncology Biology Physics, vol. 100, no. 5, ELSEVIER SCIENCE INC, 2018, pp. 1349–1349.
URI
https://scholars.duke.edu/individual/pub1311348
Source
wos
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
100
Published Date
Start Page
1349
End Page
1349

Head and Neck Cancers, Version 1.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.
Authors
Pfister, DG; Spencer, S; Brizel, DM; Burtness, B; Busse, PM; Caudell, JJ; Cmelak, AJ; Colevas, AD; Dunphy, F; Eisele, DW; Foote, RL; Gilbert, J; Gillison, ML; Haddad, RI; Haughey, BH; Hicks, WL; Hitchcock, YJ; Jimeno, A; Kies, MS; Lydiatt, WM; Maghami, E; McCaffrey, T; Mell, LK; Mittal, BB; Pinto, HA; Ridge, JA; Rodriguez, CP; Samant, S; Shah, JP; Weber, RS; Wolf, GT; Worden, F; Yom, SS; McMillian, N; Hughes, M
MLA Citation
Pfister, David G., et al. “Head and Neck Cancers, Version 1.2015..” J Natl Compr Canc Netw, vol. 13, no. 7, July 2015, pp. 847–55. Pubmed, doi:10.6004/jnccn.2015.0102.
URI
https://scholars.duke.edu/individual/pub1079204
PMID
26150579
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
13
Published Date
Start Page
847
End Page
855
DOI
10.6004/jnccn.2015.0102

Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines.

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).
Authors
Pfister, DG; Ang, K-K; Brizel, DM; Burtness, BA; Busse, PM; Caudell, JJ; Cmelak, AJ; Colevas, AD; Dunphy, F; Eisele, DW; Gilbert, J; Gillison, ML; Haddad, RI; Haughey, BH; Hicks, WL; Hitchcock, YJ; Kies, MS; Lydiatt, WM; Maghami, E; Martins, R; McCaffrey, T; Mittal, BB; Pinto, HA; Ridge, JA; Samant, S; Schuller, DE; Shah, JP; Spencer, S; Weber, RS; Wolf, GT; Worden, F; Yom, SS; McMillian, NR; Hughes, M; National Comprehensive Cancer Network,
MLA Citation
Pfister, David G., et al. “Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines..” Journal of the National Comprehensive Cancer Network : Jnccn, vol. 11, no. 8, Aug. 2013, pp. 917–23. Epmc, doi:10.6004/jnccn.2013.0113.
URI
https://scholars.duke.edu/individual/pub962492
Source
epmc
Published In
Jnccn Journal of the National Comprehensive Cancer Network
Volume
11
Published Date
Start Page
917
End Page
923
DOI
10.6004/jnccn.2013.0113

Analysis of pretreatment FDG-PET SUV parameters in head-and-neck cancer: tumor SUVmean has superior prognostic value.

PURPOSE: To evaluate the prognostic significance of different descriptive parameters in head-and-neck cancer patients undergoing pretreatment [F-18] fluoro-D-glucose-positron emission tomography (FDG-PET) imaging. PATIENTS AND METHODS: Head-and-neck cancer patients who underwent FDG-PET before a course of curative intent radiotherapy were retrospectively analyzed. FDG-PET imaging parameters included maximum (SUV(max)), and mean (SUV(mean)) standard uptake values, and total lesion glycolysis (TLG). Tumors and lymph nodes were defined on co-registered axial computed tomography (CT) slices. SUV(max) and SUV(mean) were measured within these anatomic regions. The relationships between pretreatment SUV(max), SUV(mean), and TLG for the primary site and lymph nodes were assessed using a univariate analysis for disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS). Kaplan-Meier survival curves were generated and compared via the log-rank method. SUV data were analyzed as continuous variables. RESULTS: A total of 88 patients was assessed. Two-year OS, LRC, DMFS, and DFS for the entire cohort were 85%, 78%, 81%, and 70%, respectively. Median SUV(max) for the primary tumor and lymph nodes was 15.4 and 12.2, respectively. Median SUV(mean) for the primary tumor and lymph nodes was 7 and 5.2, respectively. Median TLG was 770. Increasing pretreatment SUV(mean) of the primary tumor was associated with decreased disease-free survival (p = 0.01). Neither SUV(max) in the primary tumor or lymph nodes nor TLG was prognostic for any of the clinical endpoints. Patients with pretreatment tumor SUV(mean) that exceeded the median value (7) of the cohort demonstrated inferior 2-year DFS relative to patients with SUV(mean) ≤ the median value of the cohort, 58% vs. 82%, respectively, p = 0.03. CONCLUSION: Increasing SUV(mean) in the primary tumor was associated with inferior DFS. Although not routinely reported, pretreatment SUV(mean) may be a useful prognostic FDG-PET parameter and should be further evaluated prospectively.
Authors
Higgins, KA; Hoang, JK; Roach, MC; Chino, J; Yoo, DS; Turkington, TG; Brizel, DM
MLA Citation
Higgins, Kristin A., et al. “Analysis of pretreatment FDG-PET SUV parameters in head-and-neck cancer: tumor SUVmean has superior prognostic value..” Int J Radiat Oncol Biol Phys, vol. 82, no. 2, Feb. 2012, pp. 548–53. Pubmed, doi:10.1016/j.ijrobp.2010.11.050.
URI
https://scholars.duke.edu/individual/pub745438
PMID
21277108
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
82
Published Date
Start Page
548
End Page
553
DOI
10.1016/j.ijrobp.2010.11.050