Avraham Eisbruch

University of Michigan, Ann Arbor, Michigan, United States

Are you Avraham Eisbruch?

Claim your profile

Publications (305)1216.64 Total impact

  • [Show abstract] [Hide abstract]
    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; DOI:10.1001/jamaoto.2015.2049 · 1.79 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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
    [Show abstract] [Hide abstract]
    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
  • K Brock · C Lee · S Samuels · M Robbe · C Lockhart · M Schipper · M Matuszak · A Eisbruch
    [Show abstract] [Hide abstract]
    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
  • Source
    Archives of Oto-Rhino-Laryngology 05/2015; 272(10). DOI:10.1007/s00405-015-3660-3 · 1.55 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: Local and/or regional recurrence and metachronous primary tumor arising in a previously irradiated area are rather frequent events in patients with head and neck squamous cell carcinoma (HNSCC). Re-treatment is associated with an increased risk of serious toxicity and impaired quality of life (QOL) with an uncertain survival advantage. We analyzed the literature on the efficacy and toxicity of photon/electron-based external beam reirradiation for previously irradiated patients with HNSCC of non-nasopharyngeal origin. Studies were grouped according to the radiotherapy technique used for reirradiation. Patient selection criteria, target volume identification method, tumor dose, fractionation schedule, systemic therapy administration, and toxicities were reviewed. In addition to disease-related factors, current comorbidities and preexisting organ dysfunction must be considered when selecting patients for reirradiation. As morbidity from re-treatment may be considerable and differ depending on which mode of re-treatment is used, it is important to give patients information on potential morbidity outcomes so that an informed choice can be made within a shared decision-making context. With improved dose distribution and adequate imaging support, including positron emission tomography-CT, modern radiotherapy techniques may improve local control and reduce toxicity of reirradiation. A reirradiation dose of ≥60 Gy and a volume encompassing the gross tumor with up to a 5-mm margin are recommended. Concomitant administration of systemic therapeutics and reirradiation is likely to be of similar benefit as observed in large randomized studies of upfront therapy. Reirradiation, administered either with or without concurrent systemic therapy, is feasible and tolerable in properly selected patients with recurrent or a new primary tumor in a previously irradiated area of the head and neck, offering a meaningful survival (in the range of 10% to 30% at 2 years). Whenever feasible, salvage surgery is the method of choice for curative intent; patients at high-risk for local recurrence should be advised that postoperative reirradiation is expected to increase locoregional control at the expense of higher toxicity and without survival advantage compared to salvage surgery without reirradiation. © 2013 Wiley Periodicals, Inc. Head Neck, 2014.
    Head & Neck 12/2014; 37(1). DOI:10.1002/hed.23542 · 2.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Management of head and neck carcinoma from unknown primary (HNCUP) remains controversial, with neck dissection and radiotherapy (RT) or definitive RT both commonly used. The purpose of this study was to characterize HNCUP and retrospectively compare outcomes for patients treated with neck dissection+RT versus definitive RT. Methods From 1994 to 2009, 41 patients with HNCUP underwent either neck dissection+RT (n=22) or definitive RTconcurrent chemotherapy (n=19) at our institution. Treatment outcomes were compared using Kaplan-Meier methods and log-rank test. ResultsThere were no differences between patients treated with neck dissection+RT and definitive RT in overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), freedom from locoregional failure (FFLRG), or freedom from distant failure (FFDF). Among 17 patients who underwent neck dissection+RT for whom human papillomavirus (HPV) status could be determined, HPV(+) patients trended toward improved OS (p=.06) and PFS (p=.15). Conclusion Neck dissection and postoperative RT resulted in similar outcomes as definitive RT. The prognostic implications of HPV(+) nodes in HNCUP are similar to those in oropharyngeal primary cancers. (c) 2013 Wiley Periodicals, Inc. Head Neck 36: 1589-1595, 2014
    Head & Neck 11/2014; 36(11). DOI:10.1002/hed.23479 · 2.64 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S100. DOI:10.1016/j.ijrobp.2014.05.508 · 4.26 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S509. DOI:10.1016/j.ijrobp.2014.05.1562 · 4.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Magnetic resonance imaging (MRI) has been found to be better than computed tomography for defining the extent of primary gross tumor volume (GTV) in advanced nasopharyngeal cancer. It is routinely applied for target delineation in planning radiotherapy. However, the specific MRI sequences/planes that should be used are unknown. Methods Twelve patients with nasopharyngeal cancer underwent primary GTV evaluation with gadolinium-enhanced axial T1 weighted image (T1) and T2 weighted image (T2), coronal T1, and sagittal T1 sequences. Each sequence was registered with the planning computed tomography scans. Planning target volumes (PTVs) were derived by uniform expansions of the GTVs. The volumes encompassed by the various sequences/planes, and the volumes common to all sequences/planes, were compared quantitatively and anatomically to the volume delineated by the commonly used axial T1-based dataset. Results Addition of the axial T2 sequence increased the axial T1-based GTV by 12% on average (p = 0.004), and composite evaluations that included the coronal T1 and sagittal T1 planes increased the axial T1-based GTVs by 30% on average (p = 0.003). The axial T1-based PTVs were increased by 20% by the additional sequences (p = 0.04). Each sequence/plane added unique volume extensions. The GTVs common to all the T1 planes accounted for 38% of the total volumes of all the T1 planes. Anatomically, addition of the coronal and sagittal-based GTVs extended the axial T1-based GTV caudally and cranially, notably to the base of the skull. Conclusions Adding MRI planes and sequences to the traditional axial T1 sequence yields significant quantitative and anatomically important extensions of the GTVs and PTVs. For accurate target delineation in nasopharyngeal cancer, we recommend that GTVs be outlined in all MRI sequences/planes and registered with the planning computed tomography scans.
    Radiology and Oncology 09/2014; 48(3):323-30. DOI:10.2478/raon-2014-0013 · 1.91 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S101. DOI:10.1016/j.ijrobp.2014.05.510 · 4.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: We recently described the imaging characteristics of multiple confluent regional metastases (matted nodes) and found that this characteristic was associated with distant metastasis in patients with oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to determine if matted nodes are a predictive marker for distant metastasis. Methods: Radiologic lymph node characteristics on 205 patients with untreated stage III/IV with oropharyngeal SCC of whom 192 had known human papillomavirus (HPV) status underwent weekly carboplatin and paclitaxel with concomitant intensity-modulated radiation therapy (IMRT) between 2003 and 2010 with a minimum of 2-year of follow-up. Results: The 3-year disease-specific survival (DSS) for patients with matted nodes was 58% versus 97% with nonmatted nodes (p = .0001). The prevalence of matted nodes in the population was 20%. The positive predictive value of matted nodes for distant metastasis was 66%, and the negative predictive value was 99%. Conclusion: Matted nodes are a predictive marker for distant disease and can be used for planning new clinical interventions. © 2014 Wiley Periodicals, Inc. Head Neck, 2015.
    Head & Neck 09/2014; DOI:10.1002/hed.23882 · 2.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The current American Joint Committee on Cancer (AJCC) staging system may not accurately reflect survival in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to develop a system that more precisely predicts survival. Methods: CT scans from 156 patients who underwent chemoradiation for advanced-stage oropharyngeal SCC with >2 years follow-up were reviewed. We modeled patterns of nodal metastasis associated with different survival rates. We defined HPV+ N1 as a single node <6 cm, ipsilaterally, contralaterally, or bilaterally. HPV+ N2 was defined as a single node ≥6 cm or ≥2 nodes ipsilaterally/contralaterally or ≥3 nodes bilaterally. HPV+ N3 was defined as matted nodes. Results: There was no significant difference in disease-specific survival (DSS; p = .14) or overall survival (OS; p = .16) by AJCC classification. In patients grouped by HPV+ N1, HPV+ N2, and HPV+ N3 nodal classification, significant differences in DSS (100%, 92%, and 55%, respectively; p = .0001) and OS (100%, 96%, and 55%, respectively; p = .0001) were found. Conclusion: A staging system with reclassification of size, bilaterality, and matted nodes more accurately reflects survival differences in this cohort of patients. Review of the AJCC staging system with these criteria should be considered for HPV-positive oropharyngeal SCC.
    Head & Neck 08/2014; 36(9). DOI:10.1002/hed.23438 · 2.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose To describe voice and speech quality changes and their predictors in patients with locally advanced oropharyngeal cancer treated on prospective clinical studies of organ-preserving chemotherapy–intensity modulated radiation therapy (chemo-IMRT). Methods and Materials Ninety-one patients with stage III/IV oropharyngeal cancer were treated on 2 consecutive prospective studies of definitive chemoradiation using whole-field IMRT from 2003 to 2011. Patient-reported voice and speech quality were longitudinally assessed from before treatment through 24 months using the Communication Domain of the Head and Neck Quality of Life (HNQOL-C) instrument and the Speech question of the University of Washington Quality of Life (UWQOL-S) instrument, respectively. Factors associated with patient-reported voice quality worsening from baseline and speech impairment were assessed. Results Voice quality decreased maximally at 1 month, with 68% and 41% of patients reporting worse HNQOL-C and UWQOL-S scores compared with before treatment, and improved thereafter, recovering to baseline by 12-18 months on average. In contrast, observer-rated larynx toxicity was rare (7% at 3 months; 5% at 6 months). Among patients with mean glottic larynx (GL) dose ≤20 Gy, >20-30 Gy, >30-40 Gy, >40-50 Gy, and >50 Gy, 10%, 32%, 25%, 30%, and 63%, respectively, reported worse voice quality at 12 months compared with before treatment (P=.011). Results for speech impairment were similar. Glottic larynx dose, N stage, neck dissection, oral cavity dose, and time since chemo-IMRT were univariately associated with either voice worsening or speech impairment. On multivariate analysis, mean GL dose remained independently predictive for both voice quality worsening (8.1%/Gy) and speech impairment (4.3%/Gy). Conclusions Voice quality worsening and speech impairment after chemo-IMRT for locally advanced oropharyngeal cancer were frequently reported by patients, underrecognized by clinicians, and independently associated with GL dose. These findings support reducing mean GL dose to as low as reasonably achievable, aiming at ≤20 Gy when the larynx is not a target.
    International journal of radiation oncology, biology, physics 08/2014; 89(5). DOI:10.1016/j.ijrobp.2014.03.013 · 4.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Once-weekly gemcitabine concurrent with radiotherapy was highly effective in the treatment of head and neck cancer (HNC) but limited by high mucosal toxicity. Pre-clinical investigations suggested that delivering gemcitabine at substantially lower doses twice weekly during radiotherapy improved the therapeutic ratio. We sought to translated these preclinical findings to a phase I trial. Methods: Twenty-five patients with non-resectable HNC were scheduled to receive gemcitabine twice weekly during the last 2 weeks (total 5 infusions) of hyperfractionated radiotherapy delivering 1.2 Gy twice daily to total 76.8 Gy. Tumor biopsies to measure active intracellular (phosphorylated) gemcitabine were planned after the first drug delivery. Patients were assigned to escalating dose cohorts using the Continuous Reassessment Method. Results: Twenty-one patients evaluable for toxicity were divided into cohorts receiving twice weekly treatment with 10, 20, 33, or 50 mg/m(2) gemcitabine. Dose-limiting toxicity was grade 3-4 confluent mucositis/pharyngitis, and the maximally tolerated dose (MTD) was 20 mg/m(2). Median survival was 20 months, with no difference between cohorts receiving lower (10, 20 mg/m(2)) or higher (33, 50 mg/m(2)) gemcitabine doses. Tumor biopsies after the first drug delivery showed only a minority of tumor cells in the specimens. Conclusion: These findings validate preclinical models that show that gemcitabine is radiation sensitizer at doses far below those used for systemic chemotherapy. However, the improvement in the therapeutic ratio predicted from the preclinical study did not translate into a substantial relative increase in the MTD of the drug in the clinical phase I trial.
    Translational oncology 08/2014; 7(4):479–483. DOI:10.1016/j.tranon.2014.04.016 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We identified a standard core set of patient-reported symptoms and health-related quality-of-life (HRQOL) domains to be assessed in head and neck (H&N) cancer clinical trials. The core symptom and HRQOL domain scores were used to guide recommendations by a working group of experts as part of a National Cancer Institute Symptom Management and HRQOL Clinical Trials Planning Meeting. A PubMed search was conducted using the search terms of "health-related quality of life" and "head & neck cancer," limited to publications from January 1, 2000, to December 31, 2010. Fifty-four articles were used to guide the choice of recommendations. Twenty-nine symptoms and nine domains were identified, from which 12 H&N-specific core symptoms and HRQOL domains were recommended: swallowing, oral pain, skin changes, dry mouth, dental health, opening mouth/trismus, taste, excess/thick mucous/saliva, shoulder disability/motion, voice/hoarseness, social domain, and functional domain. This core set of 12 H&N-specific, patient-reported symptoms and HRQOL domains should be assessed in future H&N cancer clinical trials.
    JNCI Journal of the National Cancer Institute 07/2014; 106(7). DOI:10.1093/jnci/dju127 · 12.58 Impact Factor

Publication Stats

9k Citations
1,216.64 Total Impact Points


  • 1996–2015
    • 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
  • 1994–2015
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, 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