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:

Practice Recommendations for Risk-Adapted Head and Neck Cancer Radiation Therapy During the COVID-19 Pandemic: An ASTRO-ESTRO Consensus Statement.

PURPOSE: Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff. METHODS AND MATERIALS: A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases. RESULTS: In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care. CONCLUSIONS: This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.
Authors
Thomson, DJ; Palma, D; Guckenberger, M; Balermpas, P; Beitler, JJ; Blanchard, P; Brizel, D; Budach, W; Caudell, J; Corry, J; Corvo, R; Evans, M; Garden, AS; Giralt, J; Gregoire, V; Harari, PM; Harrington, K; Hitchcock, YJ; Johansen, J; Kaanders, J; Koyfman, S; Langendijk, JA; Le, Q-T; Lee, N; Margalit, D; Mierzwa, M; Porceddu, S; Soong, YL; Sun, Y; Thariat, J; Waldron, J; Yom, SS
MLA Citation
Thomson, David J., et al. “Practice Recommendations for Risk-Adapted Head and Neck Cancer Radiation Therapy During the COVID-19 Pandemic: An ASTRO-ESTRO Consensus Statement.Int J Radiat Oncol Biol Phys, vol. 107, no. 4, July 2020, pp. 618–27. Pubmed, doi:10.1016/j.ijrobp.2020.04.016.
URI
https://scholars.duke.edu/individual/pub1438213
PMID
32302681
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
107
Published Date
Start Page
618
End Page
627
DOI
10.1016/j.ijrobp.2020.04.016

Development and Implementation of an Educational Simulation Workshop in Fiberoptic Laryngoscopy for Radiation Oncology Residents.

PURPOSE: Fiberoptic laryngoscopy (FOL) is a critical tool for the diagnosis, staging, assessment of treatment response, and detection of recurrence for head and neck (H&N) malignancies. No standardized recommendations exist for procedural FOL education in radiation oncology. We therefore implemented a pilot simulation workshop to train radiation oncology residents in pertinent H&N anatomy and FOL technique. METHODS AND MATERIALS: A 2-phase workshop and simulation session was designed. Residents initially received a lecture on H&N anatomy and the logistics of the FOL examination. Subsequently, residents had a practical session in which they performed FOL in 2 simulated environments: a computerized FOL program and mannequin-based practice. Site-specific attending physicians were present to provide real-time guidance and education. Pre- and postworkshop surveys were administered to the participants to determine the impact of the workshop. Subsequently, postgraduate year (PGY)-2 residents were required to complete 6 supervised FOL examinations in clinic and were provided immediate feedback. RESULTS: Annual workshops were performed in 2017 to 2019. The survey completion rate was 14 of 18 (78%). Participants ranged from fourth-year medical students to PGY-2 to PGY-5 residents. All PGY-2 residents completed their 6 supervised FOL examinations. On a 5-point Likert scale, mean H&N anatomy knowledge increased from 2.4 to 3.7 (standard deviation = 0.6, P < .0001). Similarly, mean FOL procedural skill confidence increased from 2.2 to 3.3 (standard deviation = 0.7, P < .0001). These effects were limited to novice (fourth-year medical students to PGY-2) participants. All participants found the exercise clinically informative. CONCLUSIONS: A simulation-based workshop for teaching FOL procedural skills increased confidence and procedural expertise of new radiation oncology residents and translated directly to supervised clinical encounters. Adoption of this type of program may help to improve resident training in H&N cancer.
Authors
Price, JG; Spiegel, DY; Yoo, DS; Moravan, MJ; Mowery, YM; Niedzwiecki, D; Brizel, DM; Salama, JK
MLA Citation
Price, Jeremy G., et al. “Development and Implementation of an Educational Simulation Workshop in Fiberoptic Laryngoscopy for Radiation Oncology Residents.Int J Radiat Oncol Biol Phys, May 2020. Pubmed, doi:10.1016/j.ijrobp.2020.05.009.
URI
https://scholars.duke.edu/individual/pub1441495
PMID
32417408
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Published Date
DOI
10.1016/j.ijrobp.2020.05.009

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 (T10p,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 (Ktrans) and extracellular volume fraction (ve). 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, Ktrans, and ve were calculated using iCAD's(®) (Nashua, NH) software. The mean T10's in muscle and fat ROIs were calculated (T10m,f). To assess reliability of ROI drawing, T10p,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 Ktrans and ve from primary and node ROIs were calculated using voxel-based T10 values and T10p,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., T10m=0.958s and T10f=0.303s. The average over 14 patients of the T10's based on drawings by users A and B were T10pA=0.804s, T10nA=0.760s, T10pB=0.849s, and T10nB=0.810s. The absolute percentage difference between Ktrans and ve calculated with voxel-based T10 versus T10p,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 T10p,n=0.800s 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. 6Part1, June 2010, pp. 2683–92. Pubmed, doi:10.1118/1.3427487.
URI
https://scholars.duke.edu/individual/pub1254812
PMID
28512937
Source
pubmed
Published In
Med Phys
Volume
37
Published Date
Start Page
2683
End Page
2692
DOI
10.1118/1.3427487

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.
URI
https://scholars.duke.edu/individual/pub1143722
PMID
27598811
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
96
Published Date
Start Page
462
End Page
469
DOI
10.1016/j.ijrobp.2016.06.007

Comprehensive population-averaged arterial input function for dynamic contrast-enhanced vmagnetic resonance imaging of head and neck cancer.

PURPOSE: To generate a population-averaged arterial input function (PA-AIF) for quantitative analysis of dynamic contrast-enhanced MRI data in head and neck cancer patients. METHODS AND MATERIALS: Twenty patients underwent dynamic contrast-enhanced MRI during concurrent chemoradiation therapy. Imaging consisted of 2 baseline scans 1 week apart (B1/B2) and 1 scan after 1 week of chemoradiation therapy (Wk1). Regions of interest (ROIs) in the right and left carotid arteries were drawn on coronal images. Plasma concentration curves of all ROIs were averaged and fit to a biexponential decay function to obtain the final PA-AIF (AvgAll). Right-sided and left-sided ROI plasma concentration curves were averaged separately to obtain side-specific AIFs (AvgRight/AvgLeft). Regions of interest were divided by time point to obtain time-point-specific AIFs (AvgB1/AvgB2/AvgWk1). The vascular transfer constant (Ktrans) and the fractional extravascular, extracellular space volume (Ve) for primaries and nodes were calculated using the AvgAll AIF, the appropriate side-specific AIF, and the appropriate time-point-specific AIF. Median Ktrans and Ve values derived from AvgAll were compared with those obtained from the side-specific and time-point-specific AIFs. The effect of using individual AIFs was also investigated. RESULTS: The plasma parameters for AvgAll were a1,2 = 27.11/17.65 kg/L, m1,2 = 11.75/0.21 min(-1). The coefficients of repeatability (CRs) for AvgAll versus AvgLeft were 0.04 min(-1) for Ktrans and 0.02 for Ve. For AvgAll versus AvgRight, the CRs were 0.08 min(-1) for Ktrans and 0.02 for Ve. When AvgAll was compared with AvgB1/AvgB2/AvgWk1, the CRs were slightly higher: 0.32/0.19/0.78 min(-1), respectively, for Ktrans; and 0.07/0.08/0.09 for Ve. Use of a PA-AIF was not significantly different from use of individual AIFs. CONCLUSION: A PA-AIF for head and neck cancer was generated that accounts for differences in right carotid artery versus left carotid artery, day-to-day fluctuations, and early treatment-induced changes. The small CRs obtained for Ktrans and Ve indicate that side-specific AIFs are not necessary. However, a time-point-specific AIF may improve pharmacokinetic accuracy.
Authors
Onxley, JD; Yoo, DS; Muradyan, N; MacFall, JR; Brizel, DM; Craciunescu, OI
MLA Citation
Onxley, Jennifer D., et al. “Comprehensive population-averaged arterial input function for dynamic contrast-enhanced vmagnetic resonance imaging of head and neck cancer.Int J Radiat Oncol Biol Phys, vol. 89, no. 3, July 2014, pp. 658–65. Pubmed, doi:10.1016/j.ijrobp.2014.03.006.
URI
https://scholars.duke.edu/individual/pub1033331
PMID
24929169
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
89
Published Date
Start Page
658
End Page
665
DOI
10.1016/j.ijrobp.2014.03.006