David Manfield Brizel

Image of David Manfield Brizel

Leonard Prosnitz Professor of Radiation Oncology

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



Appointments and Affiliations

  • Leonard Prosnitz Professor of Radiation Oncology
  • Professor of Radiation Oncology
  • Professor in Surgery
  • Member of the Duke Cancer Institute

Contact Information:

  • Office Location: 05135 Morris Bldg, Durham, NC 27710
  • Office Phone: (919) 668-5637
  • Email Address: david.brizel@duke.edu

Education:

  • M.D. Northwestern University, 1983

Courses Taught:

  • LINGUIST 123FS: When the Head's in Trouble: Language, Lesions and Loss
  • NEUROSCI 123FS: When the Head's in Trouble: Language, Lesions and Loss

Representative Publications:

    • Yoo, DS; Kirkpatrick, JP; Craciunescu, O; Broadwater, G; Peterson, BL; Carroll, MD; Clough, R; MacFall, JR; Hoang, J; Scher, RL; Esclamado, RM; Dunphy, FR; Ready, NE; Brizel, DM, Prospective trial of synchronous bevacizumab, erlotinib, and concurrent chemoradiation in locally advanced head and neck cancer., Clinical cancer research : an official journal of the American Association for Cancer Research, vol 18 no. 5 (2012), pp. 1404-1414 [10.1158/1078-0432.CCR-11-1982] [abs].
    • Higgins, KA; Hoang, JK; Roach, MC; Chino, J; Yoo, DS; Turkington, TG; Brizel, DM, Analysis of pretreatment FDG-PET SUV parameters in head-and-neck cancer: tumor SUVmean has superior prognostic value., International Journal of Radiation: Oncology - Biology - Physics, vol 82 no. 2 (2012), pp. 548-553 [10.1016/j.ijrobp.2010.11.050] [abs].
    • Roach, MC; Turkington, TG; Higgins, KA; Hawk, TC; Hoang, JK; Brizel, DM, FDG-PET assessment of the effect of head and neck radiotherapy on parotid gland glucose metabolism., International Journal of Radiation: Oncology - Biology - Physics, vol 82 no. 1 (2012), pp. 321-326 [10.1016/j.ijrobp.2010.08.055] [abs].
    • Brizel, DM; Lydiatt, W; Colevas, AD, Controversies in the locoregional management of head and neck cancer., Journal of the National Comprehensive Cancer Network : JNCCN, vol 9 no. 6 (2011), pp. 653-662 [abs].
    • Brizel, DM, Head and neck cancer as a model for advances in imaging prognosis, early assessment, and posttherapy evaluation., Cancer Journal, vol 17 no. 3 (2011), pp. 159-165 [10.1097/PPO.0b013e31821e8a09] [abs].
    • Murphy, BA; Beaumont, JL; Isitt, J; Garden, AS; Gwede, CK; Trotti, AM; Meredith, RF; Epstein, JB; Le, Q-T; Brizel, DM; Bellm, LA; Wells, N; Cella, D, Mucositis-related morbidity and resource utilization in head and neck cancer patients receiving radiation therapy with or without chemotherapy., Journal of Pain and Symptom Management, vol 38 no. 4 (2009), pp. 522-532 [10.1016/j.jpainsymman.2008.12.004] [abs].
    • Brizel, DM, Targeting the future in head and neck cancer., The Lancet Oncology, vol 10 no. 3 (2009), pp. 204-205 [10.1016/S1470-2045(09)70051-8] [abs].
    • Brizel, DM; Vokes, EE, Induction chemotherapy: to use or not to use? That is the question., Seminars in Radiation Oncology, vol 19 no. 1 (2009), pp. 11-16 [10.1016/j.semradonc.2008.09.003] [abs].
    • Brizel, DM; Murphy, BA; Rosenthal, DI; Pandya, KJ; Glück, S; Brizel, HE; Meredith, RF; Berger, D; Chen, M-G; Mendenhall, W, Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma., Journal of Clinical Oncology, vol 26 no. 15 (2008), pp. 2489-2496 [10.1200/JCO.2007.13.7349] [abs].
    • Vujaskovic, Z; Thrasher, BA; Jackson, IL; Brizel, MB; Brizel, DM, Radioprotective effects of amifostine on acute and chronic esophageal injury in rodents., International Journal of Radiation Oncology, Biology, Physics, vol 69 no. 2 (2007), pp. 534-540 [10.1016/j.ijrobp.2007.05.062] [abs].
    • Brizel, DM, Pharmacologic approaches to radiation protection., Journal of Clinical Oncology, vol 25 no. 26 (2007), pp. 4084-4089 [10.1200/JCO.2007.11.5816] [abs].
    • Kasibhatla, M; Kirkpatrick, JP; Brizel, DM, How much radiation is the chemotherapy worth in advanced head and neck cancer?, International Journal of Radiation Oncology, Biology, Physics, vol 68 no. 5 (2007), pp. 1491-1495 [10.1016/j.ijrobp.2007.03.025] [abs].
    • Dewhirst, MW; Navia, IC; Brizel, DM; Willett, C; Secomb, TW, Multiple etiologies of tumor hypoxia require multifaceted solutions., Clinical cancer research : an official journal of the American Association for Cancer Research, vol 13 no. 2 Pt 1 (2007), pp. 375-377 [10.1158/1078-0432.CCR-06-2629] [abs].
    • Brizel, DM; Esclamado, R, Concurrent chemoradiotherapy for locally advanced, nonmetastatic, squamous carcinoma of the head and neck: consensus, controversy, and conundrum., Journal of Clinical Oncology, vol 24 no. 17 (2006), pp. 2612-2617 [10.1200/JCO.2005.05.2829] [abs].
    • Prosnitz, RG; Yao, B; Farrell, CL; Clough, R; Brizel, DM, Pretreatment anemia is correlated with the reduced effectiveness of radiation and concurrent chemotherapy in advanced head and neck cancer., International Journal of Radiation Oncology, Biology, Physics, vol 61 no. 4 (2005), pp. 1087-1095 [10.1016/j.ijrobp.2004.07.710] [abs].
    • Chen, L; Brizel, DM; Rabbani, ZN; Samulski, TV; Farrell, CL; Larrier, N; Anscher, MS; Vujaskovic, Z, The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats., International Journal of Radiation Oncology, Biology, Physics, vol 60 no. 5 (2004), pp. 1520-1529 [10.1016/j.ijrobp.2004.07.729] [abs].
    • Brizel, DM; Prosnitz, RG; Hunter, S; Fisher, SR; Clough, RL; Downey, MA; Scher, RL, Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer., International Journal of Radiation Oncology, Biology, Physics, vol 58 no. 5 (2004), pp. 1418-1423 [10.1016/j.ijrobp.2003.09.004] [abs].
    • Brizel, DM; Overgaard, J, Does amifostine have a role in chemoradiation treatment?, The Lancet Oncology, vol 4 no. 6 (2003), pp. 378-381 [abs].
    • Vujaskovic, Z; Feng, QF; Rabbani, ZN; Samulski, TV; Anscher, MS; Brizel, DM, Assessment of the protective effect of amifostine on radiation-induced pulmonary toxicity., Experimental Lung Research (Informa), vol 28 no. 7 (2002), pp. 577-590 [10.1080/01902140290096791] [abs].
    • Brizel, DM; Schroeder, T; Scher, RL; Walenta, S; Clough, RW; Dewhirst, MW; Mueller-Klieser, W, Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer., International Journal of Radiation Oncology, Biology, Physics, vol 51 no. 2 (2001), pp. 349-353 [abs].
    • Wasserman, T; Mackowiak, JI; Brizel, DM; Oster, W; Zhang, J; Peeples, PJ; Sauer, R, Effect of amifostine on patient assessed clinical benefit in irradiated head and neck cancer., International Journal of Radiation Oncology, Biology, Physics, vol 48 no. 4 (2000), pp. 1035-1039 [abs].
    • Brizel, DM; Wasserman, TH; Henke, M; Strnad, V; Rudat, V; Monnier, A; Eschwege, F; Zhang, J; Russell, L; Oster, W; Sauer, R, Phase III randomized trial of amifostine as a radioprotector in head and neck cancer., Journal of Clinical Oncology, vol 18 no. 19 (2000), pp. 3339-3345 [10.1200/JCO.2000.18.19.3339] [abs].
    • Carter, DL; Hebert, ME; Smink, K; Leopold, KA; Clough, RL; Brizel, DM, Double blind randomized trial of sucralfate vs placebo during radical radiotherapy for head and neck cancers., Head & Neck: Journal for the Sciences & Specialties of the Head and Neck, vol 21 no. 8 (1999), pp. 760-766 [abs].
    • Brizel, DM; Dodge, RK; Clough, RW; Dewhirst, MW, Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome., Radiotherapy & Oncology, vol 53 no. 2 (1999), pp. 113-117 [abs].
    • Brizel, DM; Albers, ME; Fisher, SR; Scher, RL; Richtsmeier, WJ; Hars, V; George, SL; Huang, AT; Prosnitz, LR, Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer., The New England journal of medicine, vol 338 no. 25 (1998), pp. 1798-1804 [10.1056/NEJM199806183382503] [abs].
    • Prosnitz, LR; Brizel, DM; Light, KL, Radiation techniques for the treatment of Hodgkin's disease with combined modality therapy or radiation alone., International Journal of Radiation Oncology, Biology, Physics, vol 39 no. 4 (1997), pp. 885-895 [abs].
    • Brizel, DM; Hage, WD; Dodge, RK; Munley, MT; Piantadosi, CA; Dewhirst, MW, Hyperbaric oxygen improves tumor radiation response significantly more than carbogen/nicotinamide., Radiation Research, vol 147 no. 6 (1997), pp. 715-720 [abs].
    • Brizel, DM; Sibley, GS; Prosnitz, LR; Scher, RL; Dewhirst, MW, Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck., International Journal of Radiation Oncology, Biology, Physics, vol 38 no. 2 (1997), pp. 285-289 [abs].
    • Brizel, DM; Scully, SP; Harrelson, JM; Layfield, LJ; Dodge, RK; Charles, HC; Samulski, TV; Prosnitz, LR; Dewhirst, MW, Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas., Cancer Research, vol 56 no. 23 (1996), pp. 5347-5350 [abs].
    • Brizel, DM; Scully, SP; Harrelson, JM; Layfield, LJ; Bean, JM; Prosnitz, LR; Dewhirst, MW, Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma., Cancer Research, vol 56 no. 5 (1996), pp. 941-943 [abs].
    • Brizel, DM; Lin, S; Johnson, JL; Brooks, J; Dewhirst, MW; Piantadosi, CA, The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation., British Journal of Cancer, vol 72 no. 5 (1995), pp. 1120-1124 [abs].
    • Brizel, DM; Rosner, GL; Prosnitz, LR; Dewhirst, MW, Patterns and variability of tumor oxygenation in human soft tissue sarcomas, cervical carcinomas, and lymph node metastases., International Journal of Radiation Oncology, Biology, Physics, vol 32 no. 4 (1995), pp. 1121-1125 [abs].
    • Brizel, DM; Rosner, GL; Harrelson, J; Prosnitz, LR; Dewhirst, MW, Pretreatment oxygenation profiles of human soft tissue sarcomas., International Journal of Radiation Oncology, Biology, Physics, vol 30 no. 3 (1994), pp. 635-642 [abs].
    • Berlangieri, SU; Brizel, DM; Scher, RL; Schifter, T; Hawk, TC; Hamblen, S; Coleman, RE; Hoffman, JM, Pilot study of positron emission tomography in patients with advanced head and neck cancer receiving radiotherapy and chemotherapy., Head & Neck: Journal for the Sciences & Specialties of the Head and Neck, vol 16 no. 4 (1994), pp. 340-346 [abs].
    • Brizel, DM; Leopold, KA; Fisher, SR; Panella, TJ; Fine, RL; Bedrosian, CL; Kenan, PD; Huang, A; Womack, T; Bjurstrom, T, A phase I/II trial of twice daily irradiation and concurrent chemotherapy for locally advanced squamous cell carcinoma of the head and neck., International Journal of Radiation Oncology, Biology, Physics, vol 28 no. 1 (1994), pp. 213-220 [abs].
    • Brizel, DM; Klitzman, B; Cook, JM; Edwards, J; Rosner, G; Dewhirst, MW, A comparison of tumor and normal tissue microvascular hematocrits and red cell fluxes in a rat window chamber model., International Journal of Radiation Oncology, Biology, Physics, vol 25 no. 2 (1993), pp. 269-276 [abs].