Evaluation of the modified Pittsburgh classification for predicting the disease-free survival outcome of squamous cell carcinoma of the external auditory canal

Background: Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate the predictive performance of this classification in relation to disease-free survival (DFS). Methods: We examined retrospective data from a nationwide Dutch cohort study including patients with primary EAC SCC. These data were combined with individual patient data from the literature. Using the combined data, the predictive performances were calculated using the c-index. Results: A total of 381 patients were included, 294 for clinical and 281 for the pathological classification analyses. The c-indices of the clinical and the pathological modified Pittsburgh classification predicting DFS were 0.725 (0.668-0.782) and 0.729 (0.672-0.786), respectively. Conclusion: The predictive performance of the modified Pittsburgh classification system as such appears to be acceptable to predict the DFS of EAC SCC. Other factors need to be added to a future model to improve the predicted performance

Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV negative nasopharyngeal carcinoma

Objectives Tumor infiltrating lymphocytes (TILs) correlate with both better and worse prognosis in solid tumors. As therapeutic modalities for nasopharyngeal carcinoma (NPC) are limited, immunotherapy could be a potential alternative. Up till now there is limited prognostic data on the role of TILs in NPC, so we assessed the prognostic role of TILs in Epstein-Barr-virus (EBV) positive and negative NPC. Methods Tissue of 92 NPCs was assessed for CD3, CD4, CD8, PD1 and PDL1 expression in the tumor's micro-environment. Correlations between clinicopathological characteristics was assessed using the Pearson X2 test, Fisher's exact test and ANOVA. Survival was analyzed with the Kaplan-Meier method and Cox regression. Differences in CD3, CD4, CD8, PD1, PDL1 counts/(co)expression between EBV positive and negative NPCs were evaluated using the Mann-Whitney U test. Two-tailed P values below 0.05 were considered statistically significant. Results EBV positive NPC contains significantly more CD3, CD4 and CD8 TILs than EBV negative NPC. In the whole NPC group, increased CD8 count is associated with better overall survival (OS) (HR 0.219 (95%CI 0.075–0.640)), but also in cases with PDL1 co-expression (HR 0.073 (95%CI 0.010–0.556)). In EBV positive NPC co-expression of CD8 and PDL1 showed better disease free survival (HR 0.407 (95%CI 0.195–0.850)) and OS (HR 0.170 (95%CI 0.037–0.787)). Conclusions Although TILs are significantly different between EBV positive and negative NPCs, it is especially composition of the infiltrate which determines prognosis. Effects of PD1 and CD8 need more study, because these findings show much potential in using immunotherapeutic modalities in NPC treatment

Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV negative nasopharyngeal carcinoma

Objectives Tumor infiltrating lymphocytes (TILs) correlate with both better and worse prognosis in solid tumors. As therapeutic modalities for nasopharyngeal carcinoma (NPC) are limited, immunotherapy could be a potential alternative. Up till now there is limited prognostic data on the role of TILs in NPC, so we assessed the prognostic role of TILs in Epstein-Barr-virus (EBV) positive and negative NPC. Methods Tissue of 92 NPCs was assessed for CD3, CD4, CD8, PD1 and PDL1 expression in the tumor's micro-environment. Correlations between clinicopathological characteristics was assessed using the Pearson X2 test, Fisher's exact test and ANOVA. Survival was analyzed with the Kaplan-Meier method and Cox regression. Differences in CD3, CD4, CD8, PD1, PDL1 counts/(co)expression between EBV positive and negative NPCs were evaluated using the Mann-Whitney U test. Two-tailed P values below 0.05 were considered statistically significant. Results EBV positive NPC contains significantly more CD3, CD4 and CD8 TILs than EBV negative NPC. In the whole NPC group, increased CD8 count is associated with better overall survival (OS) (HR 0.219 (95%CI 0.075–0.640)), but also in cases with PDL1 co-expression (HR 0.073 (95%CI 0.010–0.556)). In EBV positive NPC co-expression of CD8 and PDL1 showed better disease free survival (HR 0.407 (95%CI 0.195–0.850)) and OS (HR 0.170 (95%CI 0.037–0.787)). Conclusions Although TILs are significantly different between EBV positive and negative NPCs, it is especially composition of the infiltrate which determines prognosis. Effects of PD1 and CD8 need more study, because these findings show much potential in using immunotherapeutic modalities in NPC treatment

Preoperative low skeletal muscle mass as a risk factor for pharyngocutaneous fistula and decreased overall survival in patients undergoing total laryngectomy

BACKGROUND: Low skeletal muscle mass (SMM) is associated with postoperative complications, prolonged hospital stay, and short overall survival (OS) in surgical oncology. We aimed to investigate this association in patients undergoing total laryngectomy (TL). METHODS: A retrospective study was performed of patients undergoing TL. SMM was measured using CT or MRI scans at the level of the third cervical vertebra (C3). RESULTS: In all, 235 patients were included. Low SMM was observed in 109 patients (46.4%). Patients with low SMM had more pharyngocutaneous fistulas (PCFs) than patients with normal SMM (34.9% vs 20.6%; P = .02) and prolonged hospital stay (median, 17 vs 14 days; P < .001). In multivariate analysis, low SMM (hazards ratio, 1.849; 95% confidence interval, 1.202-2.843) and high N stage were significant prognosticators of decreased OS. CONCLUSION: Low SMM is associated with PCF and prolonged hospital stay in patients undergoing TL. Low SMM is an independent prognostic factor for shorter OS

Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I-II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC

TP53 Y220C Is a Hotspot Mutation in Oropharyngeal Squamous Cell Carcinoma

Objectives: Although TP53 mutations in head and neck squamous cell carcinoma (HNSCC) have been extensively studied, their association with the different subsites in the head and neck region has never been described. Methods: Sanger sequence analysis evaluating exons 4-9 in the TP53 gene was performed on 116 HNSCC patients. The exon location, exact codon and corresponding substitution in relation to the anatomical site (subsite) of the HNSCC were evaluated. Results: We found nonsynonymous TP53 mutations in 70% (81/116) of the patients. In oral cavity carcinomas, most mutations occurred in exon 7 (37%). In oropharyngeal and laryngeal tumors, mutations were mainly found in exons 6 and 7. The most common mutation was located in codon 220, and all of these were an Y220C mutation. Five out of nine (56%) Y220C mutations occurred in oropharyngeal tumors. Additionally, 22% of all mutations observed in oropharyngeal squamous cell carcinoma (OPSCC) consisted of Y220C mutations. Conclusion: In this study, the subsite-related distribution of TP53 mutations underlines the biological diversity between tumors arising from different anatomical regions in the head and neck region. Moreover, the Y220C mutation was by far the most prevalent TP53 mutation in HNSCC and a relative hotspot mutation in the oropharynx. (C) 2015 S. Karger AG, Base

The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap: A systematic review and retrospective multicenter analysis.

BACKGROUND: Free radial forearm flap (FRFF) reconstruction is a valuable technique in head and neck surgery, that allows closure of large defects while striving to maintain functionality. Anticoagulative drugs are often administered to improve flap survival, although evidence regarding effectiveness is lacking. OBJECTIVE OF REVIEW: To investigate the effectiveness of postoperative anticoagulants to improve survival of the FRFF in head and neck reconstruction. TYPE OF REVIEW: Systematic review and multicenter, individual patient data meta-analysis. SEARCH STRATEGY: MEDLINE, EMBASE, Web of Science and CINAHL were searched for synonyms of 'anticoagulants' and 'free flap reconstruction'. EVALUATION METHOD: Studies were critically appraised for directness of evidence and risk of bias. Authors of the highest quality publications were invited to submit their original data for meta-analysis. RESULTS: Five studies were of adequate quality and data from four studies (80%) were available for meta-analysis, describing 759 FRFF procedures. Anticoagulants used were: aspirin (12%), low-molecular weight dextran (18.3%), unfractioned heparin (28.1%), low-molecular weight heparin (49%) and prostaglandin-E1 (2.1%). Thirty-one percent did not receive anticoagulants. Flap failure occurred in 40 of 759 patients (5.3%) On univariate analysis, use of unfractioned heparin was associated with a higher rate of flap failure. However, these regimens were often administered to patients who had revision surgery of the anastomosis. In multivariate logistic regression analysis, anticoagulant use was not associated with improved flap survival or flap-related complications. CONCLUSIONS: The studied anticoagulative drugs did not improve FRFF survival or lower the rate of flap-related complications. In addition some anticoagulants may cause systemic complications. This article is protected by copyright. All rights reserved

Oropharyngeal squamous cell carcinomas differentially express granzyme inhibitors

Objectives Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have an improved prognosis compared to HPV-negative OPSCCs. Several theories have been proposed to explain this relatively good prognosis. One hypothesis is a difference in immune response. In this study, we compared tumor-infiltrating CD3+, CD4+, CD8+ T-cells, and granzyme inhibitors (SERPINB1, SERPINB4, and SERPINB9) between HPV-positive and HPV-negative tumors and the relation with survival. Methods Protein expression of tumor-infiltrating lymphocytes (TILs) (CD3, CD4, and CD8) and granzyme inhibitors was analyzed in 262 OPSCCs by immunohistochemistry (IHC). Most patients (67 %) received primary radiotherapy with or without chemotherapy. Cox regression analysis was carried out to compare overall survival (OS) of patients with low and high TIL infiltration and expression of granzyme inhibitors. Results HPV-positive OPSCCs were significantly more heavily infiltrated by TILs (p < 0.001) compared to HPV-negative OPSCCs. A high level of CD3+ TILs was correlated with a favorable outcome in the total cohort and in HPV-positive OPSCCs, while it reached no significance in HPV-negative OPSCCs. There was expression of all three granzyme inhibitors in OPSCCs. No differences in expression were found between HPV-positive and HPV-negative OPSCCs. Within the group of HPV-positive tumors, a high expression of SERPINB1 was associated with a significantly worse overall survival. Conclusion HPV-positive OPSCCs with a low count of CD3+ TILs or high expression of SERPINB1 have a worse OS, comparable with HPV-negative OPSCCs. This suggests that the immune system plays an important role in the carcinogenesis of the virally induced oropharynx tumors