David M. Brizel, MD

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• Bone and Soft Tissue Cancer
• Breast Cancer
• Gastrointestinal Cancer
• Head and Neck Cancer
• Lung Cancer
• Skin Cancer

Department / Division:
Radiation Oncology / Radiation Oncology

Address:
DUMC 3085
Durham, NC 27710

Appointment Telephone:
919-660-2100

Office Telephone:
919-668-5637

Fax Telephone:
919-668-7345

• MD, Northwestern University Feinberg School of Medicine (Illinois), 1983

• Radiation Oncology, Harvard Joint Center for Radiation Therapy (Massachusetts), 1983-1987

Clinical Interests:
Head and neck cancer, non-melanoma skin cancer, targeted therapy, tumor physiology

Research Interests:
The treatment of head and neck cancer has constituted both my principal clinical focus and the framework for my research efforts since my arrival at Duke in 1987.  I led an in house randomized trial which was one of the first to demonstrate that concurrent chemoradiation was more efficacious than radiotherapy alone for locally advanced head and neck cancer. Two aspects of this trial were unique: a) the RT alone control arm utilized accelerated hyperfractionation with doses >70 Gy many years before other clinical trials confirmed the validity of this type of fractionation as optimal single modality treatment, and b) the more effective chemoradiation arm employed lower total RT doses than the control arm. Subsequent analyses of this trial showed that loss of heterozygosity (LOH) of the M6P-IGF2R tumor suppressor gene was associated with a greater risk of recurrence after RT alone whereas patients without LOH who received RT alone recurred no more frequently than patients receiving chemoradiation. These findings suggest that this parameter could identify a favorable subset of patients with advanced disease who could be adequately treated with RT alone thus avoiding the added morbidity of chemoradiation.

Reduction of treatment induced morbidity has been a major interest of mine.  I served as the principal investigator of the pivotal randomized trial of amifostine in head and neck cancer.  This study established proof of priniciple for the feasibility of pharmacologic radioprotection.  The FDA approved this drug for protection against radiation induced xerostomia based on this trial.  Presently, I am involved in preclinical and clinical studies that are evaluating the potential role of keratinocyte growth factor for protection against radiation induced mucositis and pneumonitis. One of these is a multi-center clinical trial that is evaluating the ability of keratinocyte growth factor to diminish the severity of mouth and throat soreness that develops during chemoradiation for head and neck cancer.

I have a long term commitment to the study of tumor physiology and biology in my patients. This work has demonstrated the association between tumor hypoxia and local-regional failure in head and neck cancer and distant failure in soft-tissue sarcoma. It has also shown that elevated tumor lactate concentrations at diagnosis in patients with head and neck cancer are associated with an increased risk of metastatic failure after treatment.

I have served as co-Principal Investigator of a multinational randomized trial that tested the benefit of adding the hypoxic cell cytotoxin, tirapazamine, to concurrent chemoradiation in advanced head and neck cancer. I am conducting a unique clinical trial that combines both EGFR blockade (Tarceva) and VEGF blockade (Avastin) simultaneously with our standard regimen of hyperfractionated irradiation and concurrent cisplatin in advanced head and neck cancer.

The translational nature of my work has allowed me to become proficient in clinical care, the design and execution of clinical trials, and the conduct of laboratory investigation. It provides me with ideal opportunities to try to improve the therapeutic index of the treatments that we offer to our patients.

Representative Publications:
Brizel DM, Murphy BA, Rosenthal DI, Pandya KJ, Glück S, Brizel HE, Meredith RF, Berger D, Chen MG, Mendenhall W. Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma. J Clin Oncol. 2008 May 20;26(15):2489-96. (2008) Abstract

Vujaskovic Z, Thrasher BA, Jackson IL, Brizel MB, Brizel DM. Radioprotective effects of amifostine on acute and chronic esophageal injury in rodents. Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):534-40. (2007) Abstract

Kasibhatla M, Kirkpatrick JP, Brizel DM. How much radiation is the chemotherapy worth in advanced head and neck cancer? Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1491-5. (2007) Abstract

Dewhirst MW, Navia IC, Brizel DM, Willett C, Secomb TW. Multiple etiologies of tumor hypoxia require multifaceted solutions. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):375-7. (2007) Abstract

Brizel DM. Pharmacologic approaches to radiation protection. J Clin Oncol. 2007 Sep 10;25(26):4084-9. (2007) Abstract

Brizel DM, Esclamado R. Concurrent chemoradiotherapy for locally advanced, nonmetastatic, squamous carcinoma of the head and neck: consensus, controversy, and conundrum. J Clin Oncol. 2006 Jun 10;24(17):2612-7. (2006) Abstract

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. Int J Radiat Oncol Biol Phys. 2005 Mar 15;61(4):1087-95. (2005) Abstract

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. Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1520-9. (2004) Abstract

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. Int J Radiat Oncol Biol Phys. 2004 Apr 1;58(5):1418-23. (2004) Abstract

Brizel DM, Overgaard J. Does amifostine have a role in chemoradiation treatment? Lancet Oncol. 2003 Jun;4(6):378-81. (2003) Abstract

Vujaskovic Z, Feng QF, Rabbani ZN, Samulski TV, Anscher MS, Brizel DM. Assessment of the protective effect of amifostine on radiation-induced pulmonary toxicity. Exp Lung Res. 2002 Oct-Nov;28(7):577-90. (2002) Abstract

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. Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):349-53. (2001) Abstract

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. Int J Radiat Oncol Biol Phys. 2000 Nov 1;48(4):1035-9. (2000) Abstract

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. J Clin Oncol. 2000 Oct 1;18(19):3339-45. (2000) Abstract

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. 1999 Dec;21(8):760-6. (1999) Abstract

Brizel DM, Light K, Zhou SM, Marks LB. Conformal radiation therapy treatment planning reduces the dose to the optic structures for patients with tumors of the paranasal sinuses. Radiother Oncol. 1999 Jun;51(3):215-8. (1999) Abstract

Brizel DM, Dodge RK, Clough RW, Dewhirst MW. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol. 1999 Nov;53(2):113-7. (1999) Abstract

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. N Engl J Med. 1998 Jun 18;338(25):1798-804. (1998) Abstract

Prosnitz LR, Brizel DM, Light KL. Radiation techniques for the treatment of Hodgkin's disease with combined modality therapy or radiation alone. Int J Radiat Oncol Biol Phys. 1997 Nov 1;39(4):885-95. (1997) Abstract

Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):285-9. (1997) Abstract

Brizel DM, Hage WD, Munley, M, Dodge R, Piantadosi CA, Dewhirst, MW. Hyperbaric Oxygen Improves Tumor Radiation Response Significantly More Than Carbogen/Nicotinamide. Radiation Research. In press, 1997. (1997)

Brizel DM, Hage WD, Dodge RK, Munley MT, Piantadosi CA, Dewhirst MW. Hyperbaric oxygen improves tumor radiation response significantly more than carbogen/nicotinamide. Radiat Res. 1997 Jun;147(6):715-20. (1997) Abstract

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 Res. 1996 Dec 1;56(23):5347-50. (1996) Abstract

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 Res. 1996 Mar 1;56(5):941-3. (1996) Abstract

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. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1121-5. (1995) Abstract

Brizel DM, Lin S, Johnson JL, Brooks J, Dewhirst MW, Piantadosi CA. The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation. Br J Cancer. 1995 Nov;72(5):1120-4. (1995) Abstract

Brizel DM, Rosner GL, Harrelson J, Prosnitz LR, Dewhirst MW. Pretreatment oxygenation profiles of human soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 1994 Oct 15;30(3):635-42. (1994) Abstract

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. Int J Radiat Oncol Biol Phys. 1994 Jan 1;28(1):213-20. (1994) Abstract

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. 1994 Jul-Aug;16(4):340-6. (1994) Abstract

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. Int J Radiat Oncol Biol Phys. 1993 Jan 15;25(2):269-76. (1993) Abstract