Matthew E. Spector

Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma.

Because immune responses within the tumor microenvironment are important predictors of tumor biology, correlations of types of tumor infiltrating lymphocytes (TILs) with clinical outcomes were determined in 278 patients with head and neck squamous cell carcinoma (HNSCC).

High-Risk Human Papillomavirus Detection in Oropharyngeal, Nasopharyngeal, and Oral Cavity Cancers Comparison of Multiple Methods

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.

Matted nodes: Poor prognostic marker in oropharyngeal squamous cell carcinoma independent of HPV and EGFR status

Despite better prognosis, there is a group of oropharyngeal squamous cell carcinoma (SCC) human papillomavirus (HPV)+ patients who experience treatment failure and succumb to distant metastasis.

Refining Risk Stratification for Locoregional Failure after Chemoradiotherapy in Human Papillomavirus-Associated Oropharyngeal Cancer

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.

Clinical Outcomes and Complications Associated with TORS for OSAHS: A Benchmark for Evaluating an Emerging Surgical Technology in a Targeted Application for Benign Disease

Background: The aim of this study was to create benchmarks for evaluating clinical outcomes and complications of transoral robotic surgeries (TORS) in a multicenter setting. Methods: 243 TORS for obstructive sleep apnea/hypopnea syndrome (OSAHS) operations, carried out between 2008 and 2012, were analyzed at 7 different centers. The average hospitalization was 3.5 days. The mean patient age was 50 ± 12 years, the average BMI at the time of the procedure was 28.53 ± 3.87 and the majority of the patients were men (81%). Results: The mean preoperative and postoperative apnea/hypopnea index was 43.0 ± 22.6 and 17.9 ± 18.4, respectively (p < 0.001). The mean preoperative and postoperative Epworth Sleepiness Scale score was 12.34 ± 5.19 and 5.7 ± 3.49, respectively (p < 0.001). The mean pre- and postoperative lowest O2 saturation was 79.5 ± 8.77 and 83.9 ± 6.38%, respectively (p < 0.001). Conclusions: Patients undergoing TORS as part of a multilevel approach for the treatment of OSAHS have a reasonable expectation of success with minimal long-term morbidity.

Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

Cancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.

Reliability of post-chemoradiotherapy F-18-FDG PET/CT for prediction of locoregional failure in human papillomavirus-associated oropharyngeal cancer

OBJECTIVES Although widely adopted, the accuracy of post-chemoradiotherapy (CRT) 18F-fluorodeoxygluocose positron emission tomography/computed tomography (PET/CT) for predicting locoregional failure (LRF) in human papillomavirus-related (HPV+) oropharyngeal cancer (OPC) remains poorly characterized. We assessed the predictive value of 3-month PET/CT response for LRF in this population. MATERIALS AND METHODS 101 consecutive patients with stage III-IV HPV+ OPC who underwent definitive CRT with pre-treatment and 3-month post-CRT PET/CT at our institution from 3/2005-3/2011 were included. 3-month PET/CT response was re-classified as complete-response (CR), near-CR, or incomplete-response (<CR) for each the primary site and neck. Accuracy of 3-month PET/CT for predicting local failure (LF) and regional failure (RF) was analyzed. RESULTS Among 98 patients with an evaluable primary tumor, LF occurred in 2/67 patients with CR, 0/20 with near-CR, and 1/11 with <CR on 3-month PET/CT. Of 98 node-positive patients, RF occurred in 6/80 with CR, 2/9 with near-CR, and 0/7 with <CR in the neck at 3 months. Sensitivity and positive predictive value (PPV) of 3-month PET/CT response for LF and RF were low (0-33%), despite a high negative predictive value (NPV) (91-98%). SUVmax thresholds or % change did not improve the accuracy of 3-month PET/CT. Use of additional PET/CT surveillance after 3 months in 67 patients accurately detected both LF (96%) and RF (97%). CONCLUSIONS In the largest study to-date of PET/CT response assessment in HPV+ OPC, 3-month PET/CT response demonstrated high NPV for LRF, though with disappointing sensitivity and PPV. Subsequent PET/CT surveillance showed potential utility for early detection of LRFs.

Impact of Perineural Invasion in the Pathologically N0 Neck in Oral Cavity Squamous Cell Carcinoma

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 Design Historical cohort analysis. Setting Tertiary 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. Results Multivariate 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. Conclusions PNI 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.

Body mass index predicts success in patients undergoing transoral robotic surgery for obstructive sleep apnea.

Objective: To determine the predictors of success in patients undergoing transoral robotic surgery (TORS) and multilevel procedures for the management of moderate-to-severe obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: A total of 121 patients (83 male, 38 female) underwent TORS between 2010 and 2013. All patients had robotic assisted lingual tonsillectomy, either as stand-alone surgery or in combination with palatal Z-plasty, lateral pharyngoplasty or uvulopalatopharyngoplasty. The apnea-hypopnea index (AHI) and body mass index (BMI) were measured preoperatively and 3 months postoperatively. Success was defined as AHI <20 and a decrease in AHI by 50%. Results: There was a significant difference in the preoperative and postoperative AHI in the entire cohort (42.7 vs. 22.2; p < 0.001). Overall, 84.3% of patients had an improvement in their AHI, 51.2% of patients met the criteria for success, and 14% met the criteria for cure defined as AHI <5. When stratifying by BMI, there was a significant difference in success when comparing patients with a BMI <30 versus those with a BMI >30 (69.4 vs. 41.7%; p = 0.004). The cure rate was 15.3% in patients with a BMI <30 and 11.1% in those with a BMI >30 (p = 0.54). Conclusions: TORS lingual tonsillectomy and multilevel procedures were successful in treating moderate-to-severe OSAHS in selected patients. Preoperative BMI helps the clinician to predict success in these patients, with two thirds of patients having a clinically useful benefit. i 2014 S. Karger AG, Basel

Predictors of recurrence and survival for head and neck mucoepidermoid carcinoma

Objective To describe the epidemiology and determine the clinicopathologic predictors of recurrence and survival in patients with head and neck mucoepidermoid carcinoma (MEC). Study Design Case series with chart review. Setting Tertiary care hospital. Subjects and Methods The medical records of 101 patients who underwent surgical treatment at the University of Michigan for head and neck MEC between 1985 and 2010 were reviewed. Main outcome measures were disease-free survival (DFS), disease-specific survival (DSS), and overall survival. Clinicopathologic parameters evaluated were age, sex, subsite, histological grade, adjuvant therapy, T stage, nodal status with/without extracapsular spread, and margin status. Results Of the 101 patients, 38 parotid, 33 palate, 17 oral, 8 submandibular/sublingual, 4 orbital, and 1 parapharyngeal carcinomas were identified. All patients underwent surgical resection, 23 had postoperative radiation, and 2 had postoperative chemoradiation. The 5-year OS and DSS was 79% and 95% with a median follow-up of 72 and 45 months, respectively. Five-year DFS was 76%. On univariate analysis, histological grade was a statistically significant predictor of disease-free survival (P = .001) and overall survival (P = .04). Positive nodal status was a significant predictor of DSS (P = .004). There was no statistically significant difference in DFS, DSS, or OS based on sex, age, anatomic subsite, T stage, adjuvant therapy, and margin status. Conclusion Advanced histological grade and positive nodal status are the strongest independent predictors of prognosis in head and neck MEC patients. Further studies into the molecular biology of MEC that may account for such clinicopathological features are currently underway.