Avraham Eisbruch

Concordia University–Ann Arbor, Ann Arbor, Michigan, United States

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Publications (318)1255.1 Total impact

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    ABSTRACT: Tumor staging systems for laryngeal cancer (LC) have been developed to assist in estimating prognosis after treatment and comparing treatment results across institutions. While the laryngeal TNM system has been shown to have prognostic information, varying cure rates in the literature have suggested concern about the accuracy and effectiveness of the T-classification in particular. To test the hypothesis that tumor volumes are more useful than T classification, we conducted a retrospective review of 78 patients with laryngeal cancer treated with radiation therapy at our institution. Using multivariable analysis, we demonstrate the significant prognostic value of anatomic volumes in patients with previously untreated laryngeal cancer. In this cohort, primary tumor volume (GTVP), composite nodal volumes (GTVN) and composite total volume (GTVP + GTVN = GTVC) had prognostic value in both univariate and multivariate cox model analysis. Interestingly, when anatomic volumes were measured from CT scans after a single cycle of induction chemotherapy, all significant prognosticating value for measured anatomic volumes was lost. Given the literature findings and the results of this study, the authors advocate the use of tumor anatomic volumes calculated from pretreatment scans to supplement the TNM staging system in subjects with untreated laryngeal cancer. The study found that tumor volume assessment after induction chemotherapy is not of prognostic significance.
    Cancers 11/2015; 7(4):2236-2261. DOI:10.3390/cancers7040888

  • Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 11/2015; DOI:10.1007/s00405-015-3799-y · 1.55 Impact Factor

  • International journal of radiation oncology, biology, physics 11/2015; 93(3):S77. DOI:10.1016/j.ijrobp.2015.07.185 · 4.26 Impact Factor

  • International journal of radiation oncology, biology, physics 11/2015; 93(3):E614. DOI:10.1016/j.ijrobp.2015.07.2115 · 4.26 Impact Factor
  • E. Sapir · S. Samuels · M. Ibrahim · E. Elalfy · J.B. McHugh · A. Eisbruch ·
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    ABSTRACT: Purpose/Objective(s): To analyze patterns of failure of patients with head-and-neck cutaneous squamous cell carcinoma (HNCSCC) with radiological or clinical cranial nerve involvement (CNI) or microscopic extensive perineural invasion (PNI) treated with radiation. Materials/Methods: Review of clinical charts, radiation therapy (RT) plans, and radiologic studies of 58 patients (pts) with HNCSCC with PNI or CNI treated from 2000 through 2013 with intensity modulated RT. The pathology specimens were prospectively reviewed by the study’s pathologist (JM). Results: All patients underwent ipsilateral neck radiation: 85% postoperative RT and 15% definitive RT. Thirty-one pts had CNI: 23 pts had both radiological and clinical evidence of CNI, seven had radiological CNI without clinical symptoms, and 1 pt had focal neurological symptoms suggesting CNI without supporting MRI findings. The most commonly involved nerves were the facial nerve (VII) and the branches of the Trigeminal nerve (V1-3). CNI distribution was as follows: 1) single nerve involvement: V1 - four pts, V2 - four pts, V3- 0, VII- 10; 2) >1 nerve CNI: 13 pts, 10 of whom had involvement of V3. Twenty-three of 31 pts were treated with chemoradiation (CRT). Clinical target volume (CTV) included the involved CNs, and 16 pts had additional high-risk nerves (CN VII and V1-V3) treated electively. Median RT dose was 66 Gy (59.4-71.6 Gy). Fifteen of 31 (48%) pts with CNI had either local (N=14; 9 infield) or distant failure (N=2). Three failures were observed outside of the radiated field at the skull base ganglions (SBG). Two pts failed along nerves not electively treated that communicate with involved nerves: 1 pt had involvement of the VII nerve at presentation and failed along V2 and V3; another pt had V2 and VII involvement and failed at V1. All 8 pts with radiological involvement of SBG relapsed locally infield. Twenty-seven pts had PNI in the skin specimens without evidence of CNI. CTV in these cases included nerves innervating the involved skin dermatome but not SBG. Median dose was 60 Gy. There were 6 recurrences (22%), only 1 along the treated nerve. All local recurrences were infield. Ten of 13 (77%) pts with skip lesions failed along the involved CNs compared with 5 of 34 (15%) without skip lesions (P=.0116). On Kaplan-Meier analysis radiological CNI, clinical CNI, ≥2 nerves involved and skip lesions along the involved nerves were predictive of failure, but only clinical CNI was statistically significant on multivariate analysis (P=.0017, HR 7.9 CI 2.2 to 28.3). Conclusion: Based on these data, in cases of CNI, CTVs should include all involved and communicating nerves as well as SBG. We recommend 1) to include VII if V2 or V3 are involved and vice versa 2) to include all branches of CN V if one is involved. In cases of PNI, CTVs should include nerves supplying the involved dermatomes.
    International journal of radiation oncology, biology, physics 11/2015; 93(3):E302. DOI:10.1016/j.ijrobp.2015.07.1319 · 4.26 Impact Factor
  • E. Sapir · J. Bredfeldt · M. Schipper · K. Masi · M.M. Matuszak · A. Eisbruch ·

    International journal of radiation oncology, biology, physics 11/2015; 93(3):E617. DOI:10.1016/j.ijrobp.2015.07.2122 · 4.26 Impact Factor
  • Y. Mao · S. Samuels · E. Sapir · A. Eisbruch ·

    International journal of radiation oncology, biology, physics 11/2015; 93(3):S172. DOI:10.1016/j.ijrobp.2015.07.414 · 4.26 Impact Factor
  • S. Samuels · T. Lyden · M. Haxer · M.E. Spector · Y. Tao · M. Schipper · F. Worden · A. Eisbruch ·

    International journal of radiation oncology, biology, physics 11/2015; 93(3):E301. DOI:10.1016/j.ijrobp.2015.07.1306 · 4.26 Impact Factor
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    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 10/2015; DOI:10.1007/s00405-015-3771-x · 1.55 Impact Factor
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    ABSTRACT: Background Axitinib is an oral, potent, small molecule tyrosine kinase inhibitor with selective inhibition of VEGFR 1,2, 3, as well as inhibition of potential downstream effectors of the EGFR pathway. Given the upregulation of EGFR and VEGFR in head and neck squamous cell carcinoma, treatment with axitinib holds promise as a rational targeted therapy. Patients and Methods Patients with unresectable, recurrent or metastatic head and neck squamous cell carcinoma were included in this open label, single arm, phase II trial. Primary endpoint was 6 month progression free survival. All patients received single agent axitinib with planned dose escalation based on tolerability. A planned interim efficacy analysis was performed after enrollment of 30 patients. Results Forty-two patients were registered, 30 were evaluable. While treatment was well-tolerated with no severe bleeding events, only 19 patients were able to achieve full planned dose. The best overall response rate was 6.7 % (two partial responses) with a disease control rate of 76.7 %. Median progression free survival was 3.7 months (95 % Confidence Interval (CI): 3.5-5.7) and overall survival was 10.9 months (95 % CI: 6.4-17.8). Exploratory analysis demonstrated that patients with a smaller sum of diameter of target lesions experienced improved response rates, and better progression-free and overall survival. Conclusion Treatment with single agent axitinib should be considered due to acceptable toxicity profile and favorable median overall survival compared to standard therapies.
    Investigational New Drugs 10/2015; 33(6). DOI:10.1007/s10637-015-0293-8 · 2.92 Impact Factor
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    ABSTRACT: Background: Concurrent chemoradiotherapy (concurrent CRT) to treat head and neck cancer is associated with significant reductions of weight, mobility, and quality of life (QOL). An intervention focusing on functional exercise may attenuate these losses. Methods: We allocated patients to a 14-week functional resistance and walking program designed to maintain physical activity during cancer treatment (MPACT group; n = 11), or to usual care (control group; n = 9). Outcomes were assessed at baseline, and 7 and 14 weeks. Results: Compared to controls, the MPACT participants had attenuated decline or improvement in several strength, mobility, physical activity, diet, and QOL endpoints. These trends were statistically significant (p < .05) in knee strength, mental health, head and neck QOL, and barriers to exercise. Conclusion: In this pilot study of patients with head and neck cancer undergoing concurrent CRT, MPACT training was feasible and maintained or improved function and QOL, thereby providing the basis for larger future interventions with longer follow-up. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.
    Head & Neck 10/2015; DOI:10.1002/hed.24162 · 2.64 Impact Factor
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    ABSTRACT: Importance: This study describes the effect of adjuvant treatment on shoulder-related quality of life, leisure activities, and employment for patients undergoing neck dissection for head and neck cancer. Objective: To explore the association between treatment outcome and shoulder-related on critical daily life functions such as employment and recreation. Design, setting, and participants: Cross-sectional study of patients with head and neck cancer at a tertiary care hospital. Exposures: Level V-sparing selective neck dissection or modified radical neck dissection sparing the accessory nerve, with or without radiation therapy and/or chemotherapy. Main outcomes and measures: Patients completed the Neck Dissection Impairment Index (NDII), with scores ranging from 0 to 100 and higher scores indicating better shoulder functioning and shoulder-related quality of life, and underwent objective testing with the Constant-Murley Shoulder Function Test (Constant test) at least 12 months after the completion of all adjuvant treatment. Additional outcome measures related to physical therapy, pain medication use, leisure activity, and employment status. Results: We evaluated 167 patients who underwent 121 selective neck dissections and 46 modified radical neck dissections. The median (range) NDII score was 90 (10-100). Patients with modified radical neck dissection reported lower scores than those with selective neck dissection (85 [10-100] vs 92 [30-100]; P = .01). Multivariable analysis showed that advanced-stage disease (mean, 77 [range, 25-100] vs 87 [18-100]; P = .006), radiation therapy (80 [10-100] vs 88 [50-100]; P = .03), and chemotherapy (77 [30-100] vs 83 [18-100]; P = .002) were associated with greater shoulder impairment. The NDII and Constant test were well correlated (0.64; P < .001). Change in leisure activity was correlated with greater impairment (median [range] NDII score, 90 [18-100] for patients with no change vs 53 [10-100] for patients with change, P = .005; Constant score, 85 [12-100] vs 68 [10-88], P = .004). Patients who remained employed or resumed working had higher median (range) NDII scores (94 [10-100] and 88 [75-100], respectively) than those who limited or stopped working (70 [10-100]), which also correlates with greater shoulder impairment (P < .001). Conclusions and relevance: More aggressive treatment, either in the form of increased surgical dissection, radiation therapy, or chemotherapy, was associated with worse shoulder function and quality of life. The degree of impairment perceived by the patient and measured in objective testing was correlated with leisure activity and employment status. These findings may stimulate further investigation related to optimizing quality of life following neck dissection.
    JAMA Otolaryngology - Head and Neck Surgery 10/2015; 141(10):1-6. DOI:10.1001/jamaoto.2015.2049 · 1.79 Impact Factor
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    ABSTRACT: Retropharyngeal adenopathy (RPA) is poor prognostic factor in head and neck (HN) cancer. However, the prognostic significance of RPA in Human Papillomavirus-related (HPV+) oropharyngeal cancer (OPC) is unknown. 185 patients with HPV+OPC were assessed. Pre-therapy images reviewed by a HN radiologist to determine presence of RPA. Doses to the RPAs were determined from treatment plans. Outcomes analyzed using Kaplan-Meier method, log-rank tests, and correlations determined using Spearman's rank analyses. 29 (16%) of the HPV+patients had RPA. At median follow-up 49months, 5-year overall survival (OS), failure-free survival (FFS) and distant failure-free survival (DFFS) were 57% vs. 81% (P=0.02), 63% vs 80% (P=0.015) and 70% vs 91% (P=0.002) for patients with/without RPA, respectively. No differences observed in local/ regional control rates, exceeding 90% in both groups, and No RPA recurrences were observed. In multivariable analysis, stages T4 or N3, and RPA, were independently, statistically significantly associated with both OS and distant failure, while N2c, age, disease site, and smoking status, were not. RPA in HPV+OPC is an independent prognostic factor for distant failure, translating into worse OS. Patients with RPA may not be suitable candidates for trials of systemic treatment de-escalation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 06/2015; 116(1). DOI:10.1016/j.radonc.2015.06.006 · 4.36 Impact Factor
  • K Brock · C Lee · S Samuels · M Robbe · C Lockhart · M Schipper · M Matuszak · A Eisbruch ·
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    ABSTRACT: Tools are now available to perform daily dose assessment in radiotherapy, however, guidance is lacking as to when to replan to limit increase in normal tissue dose. This work performs statistical analysis to provide guidance for when adaptive replanning may be necessary for head/neck (HN) patients. Planning CT and daily kVCBCT images for 50 HN patients treated with VMAT were retrospectively evaluated. Twelve of 50 patients were replanned due to anatomical changes noted over their RT course. Daily dose assessment was performed to calculate the variation between the planned and delivered dose for the 38 patients not replanned and the patients replanned using their delivered plan. In addition, for the replanned patients, the dose that would have been delivered if the plan was not modified was also quantified. Deviations in dose were analyzed before and after replanning, the daily variations in patients who were not replanned assessed, and the predictive power of the deviation after 1, 5, and 15 fractions determined. Dose deviations were significantly reduced following replanning, compared to if the original plan would have been delivered for the entire course. Early deviations were significantly correlated with total deviations (p<0.01). Using the criteria that a 10% increase in the final delivered dose indicates a replan may be needed earlier in the treatment course, the following guidelines can be made with a 90% specificity after the first 5 fractions: deviations of 7% in the mean dose to the inferior constrictors and 5% in the mean dose to the parotid glands and submandibular glands. No significant dose deviations were observed in any patients for the CTV _70Gy (max deviation 4%). A 5-7% increase in mean dose to normal tissues within the first 5 fractions strongly correlate to an overall deviatios in the delivered dose for HN patients. This work is funded in part by NIH 2P01CA059827-16.
    Medical Physics 06/2015; 42(6):3590. DOI:10.1118/1.4925522 · 2.64 Impact Factor
  • J S Bredfeldt · E Sapir · K J Masi · M J Schipper · A Eisbruch · M M Matuszak ·
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    ABSTRACT: Observations in our clinic have suggested a trend towards increased skin-toxicity for head and neck (HN) patients treated with Volumetric Modulated Arc Therapy (VMAT) compared with Intensity Modulated Radiation Therapy (IMRT). Here, we report on these observations and quantify surface dose differences between VMAT and IMRT treatment plans for HN cancer patients. We retrospectively compared skin-toxicity scores gathered by the treating physician according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0) for head and neck squamous cell carcinoma (HNSCC) patients treated with IMRT (102) and VMAT (88) . A Cochran-Armitage test evaluated the relationship between treatment modality, chemotherapy and toxicity. Six patients with grade 3 skin-toxicities were selected from this cohort and the target/organ at risk volumes were transferred onto an anthropomorphic phantom using a deformable image registration based atlas (SmartSegmentation, Varian Medical). Two-arc VMAT and 9-field IMRT plans were optimized and delivered to the anthropomorphic phantom to produce similar, clinically-acceptable, dose distributions. Surface dose was measured using optically-stimulated luminescent dosimeters placed at 2 positions on the phantom's neck which were identical between VMAT and IMRT deliveries. N-factor ANOVA was performed to identify statistically significant differences in surface dose. Our retrospective study showed a marginally significant higher skin-toxicity (Grade≥ 2) for VMAT compared with IMRT (35%vs.20%, p=0.06) for patients treated with radiation alone. Phantom measurements showed a significant effect of treatment modality on surface dose (F=42.5,p<0.001) with VMAT delivering 8% higher surface doses on average. No interaction was found between use of a thermoplastic mask and treatment with VMAT (F=0.02,p=0.884). This work indicates that marginal increases in skin dose and subsequent toxicity may be expected from HN patients treated with VMAT compared with IMRT. Our results motivate the need for techniques to spare the skin during VMAT treatment planning and for the early assessment of skin-toxicity.
    Medical Physics 06/2015; 42(6):3742. DOI:10.1118/1.4926298 · 2.64 Impact Factor
  • D You · M Aryal · S Samuels · A Eisbruch · Y Cao ·
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    ABSTRACT: A previous study showed that large sub-volumes of tumor with low blood volume (BV) (poorly perfused) in head-and-neck (HN) cancers are significantly associated with local-regional failure (LRF) after chemoradiation therapy, and could be targeted with intensified radiation doses. This study aimed to develop an automated and scalable model to extract voxel-wise contrast-enhanced temporal features of dynamic contrastenhanced (DCE) MRI in HN cancers for predicting LRF. Our model development consists of training and testing stages. The training stage includes preprocessing of individual-voxel DCE curves from tumors for intensity normalization and temporal alignment, temporal feature extraction from the curves, feature selection, and training classifiers. For feature extraction, multiresolution Haar discrete wavelet transformation is applied to each DCE curve to capture temporal contrast-enhanced features. The wavelet coefficients as feature vectors are selected. Support vector machine classifiers are trained to classify tumor voxels having either low or high BV, for which a BV threshold of 7.6% is previously established and used as ground truth. The model is tested by a new dataset. The voxel-wise DCE curves for training and testing were from 14 and 8 patients, respectively. A posterior probability map of the low BV class was created to examine the tumor sub-volume classification. Voxel-wise classification accuracy was computed to evaluate performance of the model. Average classification accuracies were 87.2% for training (10-fold crossvalidation) and 82.5% for testing. The lowest and highest accuracies (patient-wise) were 68.7% and 96.4%, respectively. Posterior probability maps of the low BV class showed the sub-volumes extracted by our model similar to ones defined by the BV maps with most misclassifications occurred near the sub-volume boundaries. This model could be valuable to support adaptive clinical trials with further validation. The framework could be extendable and scalable to extract temporal contrastenhanced features of DCE-MRI in other tumors. We would like to acknowledge NIH for funding support: UO1 CA183848.
    Medical Physics 06/2015; 42(6):3321. DOI:10.1118/1.4924327 · 2.64 Impact Factor
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    Archives of Oto-Rhino-Laryngology 05/2015; 272(10). DOI:10.1007/s00405-015-3660-3 · 1.55 Impact Factor
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    ABSTRACT: To determine whether matted nodes (MNs) uniquely identify HPV+ oropharyngeal cancer (OPC) patients at disproportionately high distant failure (DF) risk who may benefit from intensified systemic therapy. 178 stage III/IV HPV+ OPC patients who completed definitive chemoradiotherapy were stratified by risk-group (low-risk=T1-3/N0-2c/<10 pack-years; intermediate-risk=T1-3/N0-2c/≥10 pack-years; high-risk=T4 or N3). Prognostic impact of MNs was assessed. At 52-months median follow-up, event rates with and without MNs were: locoregional failure (LRF): 23.3% vs. 12.8%(p=0.16), DF: 50.0% vs. 1.4%(p<0.01), any failure: 73.3% vs. 14.2%(p<0.01); cause-specific-mortality: 56.7% vs. 5.4%(p<0.01), and death: 56.7% vs. 13.5%(p<0.01). In multivariate analyses including risk-group and individual risk-factors, MNs were the strongest predictor for all endpoints except LRF. Among patients without MNs, risk-group discriminated LRF (at 3-years: low-risk=2.0%, intermediate-risk=14.4%, high-risk=24.2%; p<0.01), but not DF (low-risk=0.0%, intermediate-risk=2.1%, high-risk=3.8%; p=0.53). MNs portended dramatically increased DF and death risks in HPV+ OPC, identifying a candidate population for consideration of chemo-intensification. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Head & Neck 04/2015; DOI:10.1002/hed.24105 · 2.64 Impact Factor
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    ABSTRACT: To evaluate long-term health-related quality of life (HRQOL) in 2 prospective studies of chemo-intensity modulated radiation therapy (chemo-IMRT) for oropharyngeal cancer (OPC). Of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT, 69 were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL (HNQOL) questionnaire, the University of Washington quality of life (UWQOL) questionnaire, and the Xerostomia Questionnaire (XQ), previously administered from baseline through 2 years in the parent studies, were readministered at long-term follow-up, along with the Short-Form 36. Long-term changes in HRQOL from before treatment and 2 years were evaluated. Forty patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed human papillomavirus-positive OPC. Long term, no clinically significant worsening was detected in mean HRQOL scores compared with 2 years, with stable or improved HRQOL from before treatment in nearly all domains. "Moderate" or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom from percutaneous endoscopic gastrostomy tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. Eleven percent and 14% of patients reported "moderate" or "severe" long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors. At more than 6 years' median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared with both before treatment and 2-year follow-up. New late toxicity after 2 years was uncommon. Further emphasis on sparing the swallowing organs may yield additional HRQOL gains for long-term OPC survivors. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 04/2015; 91(5). DOI:10.1016/j.ijrobp.2014.12.045 · 4.26 Impact Factor
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    ABSTRACT: Background. The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for non-metastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. Methods. The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols vs. radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for non-nasopharyngeal HNSCC was extracted. In the case of non-randomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses. Results. Eleven randomized trials and 7 non-randomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p=0.027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses. Conclusion. Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Head & Neck 03/2015; DOI:10.1002/hed.24026 · 2.64 Impact Factor

Publication Stats

10k Citations
1,255.10 Total Impact Points


  • 1996-2015
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • University of Michigan
      • • Department of Radiation Oncology
      • • Department of Otolaryngology - Head and Neck Surgery
      • • Department of Radiology
      • • Department of Biostatistics
      Ann Arbor, Michigan, United States
    • Memorial Hospital Colorado Springs
      Colorado Springs, Colorado, United States
  • 2010
    • Assiut University
      • South Egypt Cancer Institute
      Asyūţ, Muhafazat Asyut, Egypt
  • 2006
    • Texas A&M University - Galveston
      Galveston, Texas, United States
  • 1987-2006
    • University of Texas MD Anderson Cancer Center
      • Department of Clinical Immunology
      Houston, Texas, United States
  • 1993-1994
    • Washington University in St. Louis
      • Department of Radiation Oncology
      San Luis, Missouri, United States