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Background: Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown.Methods: We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788-6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion.Results: Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/- CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling.Conclusion: Collectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of oropharyngeal squamous cell carcinoma continues to rise with the majority of patients receiving definitive or adjunctive radiation. For patients with locoregional recurrence after radiation, optimal treatment involves salvage surgery. The aim of this study is to identify factors that predict survival to ultimately improve patient selection for salvage surgery. Methods: Retrospective cohort study at an NCI-designated cancer center. We analyzed patients with a history of head and neck radiation who presented with persistent/recurrent or second primary disease requiring salvage oropharyngeal resection from 1998–2017 (n = 120). Patients were stratified into three classes based on time to recurrence and presence of laryngopharyngeal dysfunction. Primary outcomes were 5-year overall survival (OS) and disease specific survival (DSS). Results: Median OS was 27 months (median follow-up 20 months). Five-year OS was 47% for class I (recurrence > 2 years), 26% for class II (recurrence ≤ 2 years), and 0% for class III (recurrence ≤ 2 years and laryngopharyngeal dysfunction), (p < 0.0001). Five-year DSS showed significant differences between classes (p < 0.0001). On multivariate analysis, class remained predictive of OS (p = 0.04– < 0.001) and DSS (p = 0.04–0.001). Adjuvant radiation after salvage surgery with negative margins showed superior OS (71% vs. 28%, p = 0.01) and DSS (83% vs 37%, p = 0.02) compared to surgery alone and was a significant predictor of improved survival on multivariate analysis (HR 0.1, p = 0.04). Conclusion: This study identified a subset of patients with oropharyngeal cancer recurrence within two years of initial treatment and with laryngopharyngeal dysfunction who have poor outcomes for salvage surgery. [ABSTRACT FROM AUTHOR]

Objectives Examine the postoperative growth rate of residual juvenile angiofibroma (JA) in a large series of patients relative to pediatric growth parameters and other prognostic factors. Establish an algorithm for postoperative surveillance of patients with JA. Design Retrospective case series. Setting Tertiary referral academic center. Participants Pediatric patients undergoing surgical resection of JA between September 2005 and June 2015. Main Outcome Measures Postoperative recurrence and tumor growth rates. Results Thirty-eight patients were identified with a mean follow-up of 24.1 months. Sixty-eight percent (26/34) of patients achieved gross total resection, and 32% (12/38) had persistent postoperative disease. Of those with postoperative residual tumor, all had preoperative skull base involvement and residual blood supply from the internal carotid artery following embolization. Sixty-seven percent (8/12) of patients with postoperative residual tumor demonstrated radiographic stability of disease with scans being completed approximately every 6 months. Radiographic rates of disease progression ranged from 4.1 to 9.22 mm/year. Conclusions Patients with preoperative skull base involvement and residual vascularity following preoperative embolization are more likely to have residual postoperative disease, and a longer postoperative follow-up is warranted in these patients. Progression of residual disease occurred approximately 7.5 months postoperatively. Younger patients may be more likely to need further intervention for postoperative residual disease, and postoperative imaging at 6-month intervals appears appropriate. [ABSTRACT FROM AUTHOR]

Objectives To compare the clinical utility of four juvenile nasal angiofibroma (JNA) staging systems in a large cohort of patients. Design Retrospective case series. Setting Tertiary referral academic center. Participants Pediatric patients undergoing surgical resection of JNAs between January 2008 and June 2015. Main Outcome Measures Intraoperative blood loss and transfusions, number of staged operations, postoperative residual disease, and recurrent disease. Results In total, 34 patients were identified; all underwent preoperative embolization followed by surgery. Of the 34 patients, 33 (97%) underwent an exclusively endoscopic surgical approach, with 6 (18%) requiring planned staged operations. Ten (29%) patients had residual disease and three (9%) required further surgical resection. Using the area under the curve (AUC) of receiver operating characteristic curves, the University of Pittsburgh Medical Center (UPMC) staging system was most predictive of patients who required staged procedures, received intraoperative transfusions, and had residual postoperative disease (AUC: 0.89, 0.88, 0.86, respectively). Conclusions The UPMC JNA staging system accounts for both route of skull base extension and tumor vascularity, which are two important tumor attributes in the age of preoperative embolization and endoscopic endonasal surgery. The UPMC staging system is a reliable modern staging system that closely reflects prognostic information and aids in surgical planning. [ABSTRACT FROM AUTHOR]

Objectives: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery.Materials and Methods: This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests.Results: Only CD103+ TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r2 = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103+ TILs and/or high PD-L1 CPS staining.Conclusion: Among patients with persistent or recurrent LSCC, CD103+ TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103+ TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future. [ABSTRACT FROM AUTHOR]