Avraham Eisbruch

University of Michigan, Ann Arbor, Michigan, United States

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Publications (259)893.65 Total impact

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    ABSTRACT: 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.
    Radiology and Oncology 09/2014; 48(3):323-30. · 1.60 Impact Factor
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    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/m2 gemcitabine. Dose-limiting toxicity was grade 3-4 confluent mucositis/pharyngitis, and the maximally tolerated dose (MTD) was 20 mg/m2. Median survival was 20 months, with no difference between cohorts receiving lower (10, 20 mg/m2) or higher (33, 50 mg/m2) 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.
  • Jeffrey M Vainshtein, Avraham Eisbruch
    Oral Oncology 04/2014; · 2.70 Impact Factor
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    ABSTRACT: Background Although typically associated with a favorable prognosis, a minority of human papillomavirus (HPV)-related (+) oropharyngeal cancers recur after chemoradiation. We postulated that a minor HPV-negative tumor subfraction may be responsible for recurrences of HPV+ oropharyngeal cancer.Methods Paired untreated primary and recurrent tumor specimens were identified for 37 patients with oropharyngeal cancer who received definitive chemoradiotherapy at our institution. Concordance in HPV/p16 expression between primary and recurrent tumors was assessed.ResultsAmong 31 patients with HPV+/p16+ primary tumors, 30 (97%) retained evidence of both HPV and p16 expression at recurrence (27 HPV+/p16+; 3 HPV+/p16-partial). One (3%) initially HPV+/p16+ patient developed an HPV-negative/p16-negative lung squamous cell carcinoma (SCC), representing either a discordant oropharyngeal cancer metastasis or second primary tumor.ConclusionHPV-related oropharyngeal cancers retain HPV+/p16+ expression at recurrence. Our results fail to provide evidence that a minor HPV-negative tumor subfraction is responsible for biologically aggressive behavior of HPV+ oropharyngeal cancer that recurs after chemoradiation. © 2013 Wiley Periodicals, Inc. Head Neck, 2014
    Head & Neck 04/2014; · 2.83 Impact Factor
  • James Balter, Avraham Eisbruch
    International journal of radiation oncology, biology, physics 04/2014; 88(5):1214. · 4.59 Impact Factor
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    ABSTRACT: Purpose To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.
    International journal of radiation oncology, biology, physics 01/2014; 88(3):580–588. · 4.59 Impact Factor
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    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 01/2014; · 4.59 Impact Factor
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    ABSTRACT: Background To determine whether the addition of molecular and imaging biomarkers to established clinical risk factors could help predict locoregional failure (LRF) after chemoradiation in human papillomavirus (HPV)-related (+) oropharyngeal cancer (OPC) and improve patient selection for locoregional treatment de-intensification. Methods HPV status was determined for 198 consecutive patients with stage III/IV OPC treated with definitive chemoradiation from 5/2003 to 10/2010. The impact of pre-therapy epidermal growth factor receptor (EGFR) overexpression; imaging biomarkers including primary tumor and nodal maximum standardized uptake values on FDG-PET, gross tumor volumes, and matted nodes; and clinical factors on LRF (including residual disease at adjuvant neck dissection) was assessed. Results Primary tumors were HPV+ in 184 patients and HPV-negative in 14. EGFR overexpression was related to HPV-negative status and was univariately associated with LRF in the overall population, but was neither retained in the multivariate model after adjustment for HPV status, nor associated with LRF in HPV+ patients. Similarly, imaging biomarkers were univariately associated with LRF, but correlated with T-stage and/or N-stage and did not remain predictive in HPV+ patients after adjustment for T4- and N3-stages, which were the only significant predictors of LRF on multivariate analysis. Among HPV+ patients with non-T4- or N3-stages, only minimal smoking was associated with decreased LRF. Conclusions The prognostic impact of EGFR overexpression and imaging biomarkers on LRF was predominantly related to their association with HPV-negative status and T- or N-stage, respectively. Among HPV+ OPC patients treated with uniform chemoradiation, only T4-stage, N3-stage, and smoking contributed to risk-stratification for LRF.
    Oral Oncology 01/2014; · 2.70 Impact Factor
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    ABSTRACT: IMPORTANCE The University of Michigan has investigated the use of induction selection (IS) with chemoradiotherapy (CRT) for patients who respond to CRT and found this approach effective in the management of advanced laryngeal cancer. The IS approach was extended to oral cavity squamous cell carcinoma (OCSCC) to help understand whether organ preservation or survival benefit resulted. OBJECTIVE To evaluate the efficacy of an IS protocol vs primary surgical extirpation and selective postoperative radiotherapy for advanced OCSCC. DESIGN AND SETTING Retrospective matched cohort study at a tertiary care hospital. PARTICIPANTS Nineteen patients with resectable stages III and IV OCSCC were enrolled into a phase 2 IS trial. Patients with a response of at least 50% underwent concurrent CRT; those with a response of less than 50% underwent surgical treatment and radiotherapy. A comparison cohort of patients treated with primary surgical extirpation during a similar time period was frequency matched for inclusion criteria and patient characteristics to those patients included from the phase 2 IS trial. No difference was noted in age, sex, pretreatment American Joint Committee on Cancer stage, T and N classifications, smoking status, alcohol consumption, or tumor subsite between the IS and surgical cohorts. Median follow-up was 9.4 years in the IS cohort and 7.1 years in the surgical cohort. INTERVENTIONS Induction selection and CRT vs primary surgical extirpation with or without postoperative radiotherapy. MAIN OUTCOMES AND MEASURES Overall and disease-specific survival and locoregional control. RESULTS The Kaplan-Meier estimate for overall survival at 5 years was 32% in the IS cohort and 65% in the surgical cohort. The Kaplan-Meier estimate for disease-specific survival at 5 years was 46% in the IS cohort and 75% in the surgical cohort. The Kaplan-Meier estimate for locoregional control at 5 years was 26% in the IS cohort and 72% in the surgical cohort. Multivariable analysis demonstrated significantly better overall and disease-specific survival and locoregional control outcomes (P = .03, P = .001, and P < .001, respectively) in the surgical cohort. CONCLUSIONS AND RELEVANCE Primary surgical treatment showed significantly better survival and locoregional control compared with IS in this matched patient cohort. Despite success of organ preservation IS protocols in the larynx, comparative survival analysis of an IS protocol vs primary surgical extirpation for OCSCC demonstrates significantly better outcomes in the surgical cohort. These findings support surgery as the principal treatment for OCSCC.
    JAMA otolaryngology-- head & neck surgery. 12/2013;
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    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 11/2013; · 2.83 Impact Factor
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    ABSTRACT: IMPORTANCE Human papillomaviruses are now recognized as an etiologic factor in a growing subset of head and neck cancers and have critical prognostic importance that affects therapeutic decision making. There is no universally accepted gold standard for high-risk HPV (hrHPV) assessment in formalin-fixed, paraffin-embedded (FFPE) tissue specimens, nor is there a clear understanding of the frequency or role of hrHPV in sites other than oropharynx. OBJECTIVE To determine the optimal assessment of hrHPV in FFPE head and neck tumor tissue specimens. DESIGN, SETTING, PARTICIPANTS In the setting of a large Midwestern referral center, assessment of hrHPV by p16 immunohistochemical staining, in situ hybridization, and polymerase chain reaction (PCR)-MassArray (PCR-MA), with L1 PGMY-PCR and sequencing to resolve method discordance, was conducted for 338 FFPE oropharyngeal, nasopharyngeal, and oral cavity tumor tissue specimens. Relative sensitivity and specificity were compared to develop a standard optimal test protocol. Tissue specimens were collected from 338 patients with head and neck cancer treated during the period 2001 through 2011 in the departments of Otolaryngology, Radiation Oncology, and Medical Oncology. INTERVENTION Patients received standard therapy. MAIN OUTCOMES AND MEASURES Optimal hrHPV identification, detection, and activity in head and neck cancers. RESULTS Using combined PCR-MA with L1 PGMY-PCR and sequencing for conclusive results, we found PCR-MA to have 99.5% sensitivity and 100% specificity, p16 to have 94.2% sensitivity and 85.5% specificity, and in situ hybridization to have 82.9% sensitivity and 81.0% specificity. Among HPV-positive tumors, HPV16 was most frequently detected, but 10 non-HPV16 types accounted for 6% to 50% of tumors, depending on the site. Overall, 86% of oropharynx, 50% of nasopharynx, and 26% of oral cavity tumors were positive for hrHPV. CONCLUSIONS AND RELEVANCE PCR-MA has a low DNA (5 ng) requirement effective for testing small tissue samples; high throughput; and rapid identification of HPV types, with high sensitivity and specificity. PCR-MA together with p16INK4a provided accurate assessment of HPV presence, type, and activity and was determined to be the best approach for HPV testing in FFPE head and neck tumor tissue specimens.
    JAMA otolaryngology-- head & neck surgery. 10/2013;
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    ABSTRACT: Objective Patients with oral cavity squamous cell carcinoma (OCSCC) undergo adjuvant radiation for pathologically high-risk features including positive nodal disease and extracapsular spread (ECS). In the absence of these high-risk features, our objective was to determine if perineural invasion (PNI) is an independent risk factor and if adjuvant radiation (XRT) improves disease control rates.Study DesignHistorical cohort analysis.SettingTertiary university hospital.Methods Eighty-eight OCSCC patients (46 males, 42 females; mean age = 56.7 years; median follow-up = 4.6 years) treated surgically with pathologically N0 (pN0) necks were studied. Overall, 23% (20/88) were pN0/PNI+ and of those with PNI, 70% (14/20) underwent XRT. Survival analysis using Kaplan-Meier followed by multivariable Cox models was performed.ResultsMultivariate analysis verified PNI to be associated with worse disease-free interval (DFI) (P = .012) and local-regional control (LRC) (P = .005) and perivascular invasion (PVI) associated with worse DFI (P = .05). Among pN0/PNI+ patients, those who received XRT demonstrated significantly improved DFI (mean = 6.5 years vs 1.7 years; P = .014) and LRC (mean 6.7 years vs 1.9 years; P = .047). There was no improvement in overall survival (P = .68) or disease-specific survival (P = .8) in those receiving XRT.ConclusionsPNI is an independent adverse risk factor in the absence of nodal metastasis and extracapsular spread. We observed a statistically significantly longer DFI and LRC when patients were treated with adjuvant radiation.
    Otolaryngology Head and Neck Surgery 10/2013; · 1.73 Impact Factor
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    Archives of Oto-Rhino-Laryngology 10/2013; · 1.29 Impact Factor
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    ABSTRACT: Objectives To demonstrate the advantages of the thoracodorsal artery scapular tip autogenous transplant (Tdast) for patients requiring restoration of the orbital aesthetic subunit. Design Prospective case series. Setting Tertiary center. Participants Ten patients (M:F,6:4) with a mean age of 56 years (range, 21 to 78 years) underwent restoration of the orbital aesthetic subunit and radiation therapy between 2001 and 2008. Main Outcome Measures The two reconstructive advantages of the thoracodorsal artery system of flaps for orbital reconstruction are a long pedicle and the suitability of the scapula tip to meet the three-dimensional requirements of the orbit. Patients were assessed 1 year or more after treatment for cosmetic outcome, work status, and socialization. Results Eight of 10 patients benefited from the three-dimensional nature of the scapula tip bone and 7 of 10 avoided vein grafting. Four of five evaluable patients reported "frequently" socializing outside their home. Four of five evaluable patients working before undergoing their treatment were able to return to work posttreatment. Seven of nine patients with postoperative photographs had minimal or no facial contour deformity. Conclusions The Tdast can restore orbital contour without osteotomy, and the thoracodorsal artery system of flaps has a long vascular pedicle that reduces vein grafting. Patients have an acceptable cosmetic result and return to preoperative work status and socialization.
    Journal of neurological surgery. Part B, Skull base. 10/2013; 74(5):279-85.
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    ABSTRACT: Doses actually delivered to the parotid glands during radiation therapy often exceed planned doses. We hypothesized that the delivered doses correlate better with parotid salivary output than the planned doses, used in all previous studies, and that determining these correlations will help make decisions regarding adaptive radiation therapy (ART) aimed at reducing the delivered doses. In this prospective study, oropharyngeal cancer patients treated definitively with chemoirradiation underwent daily cone-beam computed tomography (CBCT) with clinical setup alignment based on the C2 posterior edge. Parotid glands in the CBCTs were aligned by deformable registration to calculate cumulative delivered doses. Stimulated salivary flow rates were measured separately from each parotid gland pretherapy and periodically posttherapy. Thirty-six parotid glands of 18 patients were analyzed. Average mean planned doses was 32 Gy, and differences from planned to delivered mean gland doses were -4.9 to +8.4 Gy, median difference +2.2 Gy in glands in which delivered doses increased relative to planned. Both planned and delivered mean doses were significantly correlated with posttreatment salivary outputs at almost all posttherapy time points, without statistically significant differences in the correlations. Large dispersions (on average, SD 3.6 Gy) characterized the dose-effect relationships for both. The differences between the cumulative delivered doses and planned doses were evident at first fraction (r=.92, P<.0001) because of complex setup deviations (eg, rotations and neck articulations), uncorrected by the translational clinical alignments. After daily translational setup corrections, differences between planned and delivered doses in most glands were small relative to the SDs of the dose-saliva data, suggesting that ART is not likely to gain measurable salivary output improvement in most cases. These differences were observed at first treatment, indicating potential benefit for more complex setup corrections or adaptive interventions in the minority of patients with large deviations detected early by CBCT.
    International journal of radiation oncology, biology, physics 09/2013; · 4.59 Impact Factor
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    ABSTRACT: Background: Management of head and neck carcinoma from unknown primary (HNCUP) remains controversial, with neck dissection and radiotherapy (ND+RT) or definitive RT both commonly used. We aimed to characterize HNCUP and retrospectively compare outcomes for patients treated with ND+RT versus definitive RT. Methods: From 1994-2009, 41 HNCUP patients underwent either ND+RT (n=22) or definitive RT± concurrent chemotherapy (n=19) at our institution. Treatment outcomes were compared using Kaplan-Meier methods and log-rank test. Results: There were no differences between patients treated with ND+RT and definitive RT in overall survival (OS), progression-free survival (PFS), or locoregional-relapse-free survival, freedom-from-locoregional failure, or freedom-from-distant failure. Among 17 ND+RT patients for whom human papillomavirus (HPV) status could be determined, HPV(+) patients trended towards improved OS (p=0.06)and PFS (p=0.15). Conclusions: Neck dissection and post-op RT resulted in similar outcome as definitive RT. The prognostic implications of HPV(+) nodes in HNCUP are similar to those in oropharyngeal primary cancers. Head Neck, 2013.
    Head & Neck 08/2013; · 2.83 Impact Factor
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    ABSTRACT: Background: The impact of primary tumor volume (pTV) on local control after definitive radiotherapy (RT) for head-and-neck squamous cell carcinomas (SCCs) is unclear. Methods: Pertinent literature was reviewed to address the impact of pTV on local control after definitive RT for head-and-neck SCCs. Results: Reproducibility of pTV calculations is probably influenced by inter-observer variability and may be reduced by relying on experienced observers. The impact of pTV on local control after definitive RT is probably influenced by primary site. A relatively limited impact of pTV on local control after RT for oropharyngeal SCCs might be attributable to human papilloma virus positivity. Conclusions: pTV may be a useful parameter to select patients for treatment with definitive RT, particularly for those with laryngeal SCCs. Patients with high-volume primary cancers where the probability of local control with a functional larynx is low are likely better treated with surgery. Head Neck, 2013.
    Head & Neck 08/2013; · 2.83 Impact Factor
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    ABSTRACT: Background:The current AJCC staging system may not accurately reflect survival in patients with HPV+OPSCC. The purpose of this study is to develop a system that more precisely predicts survival. Methods:CT scans from 156 patients who underwent chemoradiation for advanced-stage OPSCC with >2years follow-up were reviewed. We modeled patterns of nodal metastasis associated with different survival rates. We defined HPV+ N1 as a single node <6cm, ipsilaterally,contralaterally or bilaterally. HPV+ N2 was defined as a single node ≥6cm or ≥2nodes ipsilaterally/contralaterally or ≥3nodes bilaterally. HPV+ N3 was defined as matted nodes. Results:There was no significant difference in DSS(p=0.14) or OS(p=0.16) by AJCC classification. In patients grouped by HPV+ N1,HPV+ N2,and HPV+ N3 nodal classification, significant differences in DSS(100%,92%,55%,respectively,p=0.0001) and OS(100%,96%,55%,respectively,p=0.0001) were found. Conclusions: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+OPSCC. Head Neck, 2013.
    Head & Neck 08/2013; · 2.83 Impact Factor
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    ABSTRACT: Swallowing dysfunction following chemoradiation for head and neck cancer is a major cause of morbidity and reduced quality of life. This review discusses 3 strategies that may improve posttreatment swallowing function. The literature was assessed by a multiauthor team that produced evidence-based recommendations. (1) Prospective and randomized studies with small cohorts show a trend toward benefits for a preventative exercise program addressing oral and pharyngeal structures. (2) Prospective and retrospective data indicate that better swallowing outcomes are likely when nasogastric tubes are used in preference to gastrostomy tubes to supplement enteral nutrition during chemoradiation. (3) Emerging prospective data with mature results on small cohorts support the hypothesis that radiation dose restriction to swallowing structures using intensity-modulated radiation therapy techniques leads to better swallow outcomes. This study discusses 3 strategies for improving swallow-related outcomes in patients undergoing chemoradiation for head and neck cancer and identifies areas for future research. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.
    Head & Neck 07/2013; · 2.83 Impact Factor
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    ABSTRACT: OBJECTIVES/HYPOTHESIS: To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial. STUDY DESIGN: Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers, and correlations with outcome were determined. METHODS: Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers. RESULTS: Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (P = 0.0003). CONCLUSIONS: Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2013.
    The Laryngoscope 06/2013; · 1.98 Impact Factor

Publication Stats

6k Citations
893.65 Total Impact Points

Institutions

  • 1996–2014
    • University of Michigan
      • Department of Radiation Oncology
      Ann Arbor, Michigan, United States
    • Memorial Hospital Colorado Springs
      Colorado Springs, Colorado, United States
  • 1994–2014
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2013
    • Uludag University
      Boursa, Bursa, Turkey
    • University of Florida
      • Department of Radiation Oncology
      Gainesville, Florida, United States
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      Newcastle-on-Tyne, England, United Kingdom
    • The Ohio State University
      • Division of Hospital Medicine
      Columbus, OH, United States
  • 2012
    • Albert Einstein College of Medicine
      • Oncology
      New York City, NY, United States
    • The University of Calgary
      Calgary, Alberta, Canada
    • Institute of Oncology Ljubljana
      Lubliano, Ljubljana, Slovenia
  • 2010–2011
    • Fudan University
      • Cancer Hospital
      Shanghai, Shanghai Shi, China
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
    • Assiut University
      • South Egypt Cancer Institute
      Asyūţ, Muhafazat Asyut, Egypt
  • 1993–2010
    • University of Washington Seattle
      • Department of Radiation Oncology
      Seattle, WA, United States
    • Washington University in St. Louis
      • Department of Radiation Oncology
      San Luis, Missouri, United States
  • 2006
    • University of Texas MD Anderson Cancer Center
      • Department of Head and Neck Surgery
      Houston, TX, United States
  • 2005
    • University of Toronto
      • Department of Radiation Oncology
      Toronto, Ontario, Canada