Diagnostic accuracy of computed tomography findings for patients undergoing salvage total laryngectomy

Conclusions: Computed tomography (CT) imaging has clear limitations for the diagnosis of cartilage invasion or tumor spread in recurrent laryngeal cancer. Alternative methods of pretreatment assessment are needed for recurrent laryngeal cancer. Objectives: The diagnosis and staging of recurrent laryngeal cancer, previously treated by radiation therapy (RT), remains challenging. Practically, surgeons need to depend on imaging to predict which patients will have a chance for conservation salvage laryngectomy. The purpose of the present study was to determine the accuracy of preoperative CT performed for recurrent laryngeal carcinoma evaluation following RT. Methods: This retrospective review identified 32 patients who underwent salvage total laryngectomy after RT from 1998 to 2010. For our radiologic classification of the thyroid cartilage, we analyzed the conditions as normal, sclerosis, invasion, penetration, and extralaryngeal spread and categorized the state of the arytenoids and cricoid into three possible conditions: normal, sclerosis, and destruction. Radiographic findings were correlated with pathology findings. Results: Sensitivity and specificity for the detection of the thyroid cartilage infiltration were 57% and 94%, 50% and 89% for the cricoid cartilage, and 33% and 76% for arytenoid cartilage, respectively. The accuracy of recurrent tumor classification was 59.4%. Three carcinomas were over-staged and 10 were under-staged. © 2013 Informa Healthcare

Development of TRAIL resistance by radiation-induced hypermethylation of DR4 CpG Island in recurrent laryngeal squamous cell carcinoma

Purpose There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis. Methods and Materials Using a previously established HN3 cell line from a laryngeal carcinoma patient, we generated a chronically irradiated HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting and flow cytometry were used to determine the underlying mechanism of TRAIL resistance. DR4 expression was semiquantitatively scored in a tissue microarray with 107 laryngeal cancer specimens. Methylation-specific polymerase chain reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated from each cell line. Results HN3R cells were more resistant than HN3 cells to TRAIL-induced apoptosis because of significantly reduced levels of the DR4 receptor. The DR4 staining score in 37 salvage surgical specimens after radiation failure was lower in 70 surgical specimens without radiation treatment (3.03 ± 2.75 vs 5.46 ± 3.30, respectively; P\u3c.001). HN3R cells had a methylated DR4 CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2′-deoxycytidine. Conclusion Epigenetic silencing of the TRAIL receptor by hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL resistance in recurrent laryngeal carcinoma treated with radiation. © 2014 Elsevier Inc. All rights reserved

Genomic and human papillomavirus profiling of an oral cancer cohort identifies TP53 as a predictor of overall survival.

BackgroundThe genomic landscape of head and neck cancer has been reported through The Cancer Genome Atlas project. We attempt to determine if high-risk human papillomavirus (HPV) or frequently mutated genes are correlated with survival in an oral cancer cohort.MethodsPatient demographic data along with data from final pathology was collected. Tumor DNA was analyzed using a custom Illumina targeted sequencing panel. Five high-risk HPV types were tested by qPCR. Statistical analyses were used to identify associations between patient outcome and mutational status.ResultsHigh-risk HPV types were identified in 7% of cases; HPV status was not associated with survival. Mutations were identified in TP53, TERT promoter, & PIK3CA. Mutations in TP53 were significantly associated with poorer overall survival on multi-variate analysis (p = 0.03).ConclusionsMutations in TP53 were associated with poor patient survival. Expanding our sample size may identify further predictors of outcome to direct customized cancer care