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Objective: This study aimed to determine the impact or survival of low skeletal muscle mass (SMM) among patients with oral squamous cell carcinoma (OSCC) undergoing primary surgery. Design: This study was a retrospective cohort study. Setting: Oral squamous cell carcinoma patients treated at our referral centre from April 2005 to March 2014 were examined. Participants: The cohort comprised 276 patients with OSCC undergoing primary surgery. Main outcome measures: Estimated SMM was measured by calculating the cervical skeletal muscle mass from a CT scan of the head and neck. The 5‐year overall survival (OS) and disease‐specific survival (DSS) were analysed using a multivariable Cox regression model. Results: There were 276 patients with a male‐to‐female ratio of 12:1. A low SMM (<47.5 cm2/m2) was associated with worse survival. After adjustment for other factors, the result remained robust for OS (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.14‐2.67) and disease‐specific survival (HR 1.67, 95% CI 1.04‐2.67). In the subgroup analysis, worse OS and DSS were particularly noted in male patients (HR = 1.90, 95% CI 1.22‐2.97; HR = 1.91, 95% CI 1.27‐3.19) and in those younger than 60 years of age (HR = 1.91, 95% CI 1.14‐3.22; HR = 2.12, 95% CI 1.23‐3.64) with low SMM. Conclusions: Low SMM was a significant independent factor that was associated with lower survival in patients who have oral cavity cancers and are undergoing primary surgery. Preoperative CT scans of the head and neck could be utilised to evaluate SMM, predict treatment outcomes and facilitate nutrition management. [ABSTRACT FROM AUTHOR]

Objective: We examined whether dynamic margin criteria margin‐to‐thickness (MTR) ratio has superior predictive value compared with the resection margin or tumour thickness alone in the survival outcome in oral squamous cell carcinoma (OSCC). Design: This is a retrospective cohort study. Setting: Oral squamous cell carcinoma patients treated in Kaohsiung Veterans General Hospital Cancer Center between January 2006 and December 2013. Participants: A cohort of 302 patients with OSCC who had undergone surgical management. Main Outcomes Measures: Log MTR was calculated for each patient, and survival data were analysed using a multivariable Cox regression model. Discriminative analysis was performed using chi‐square, Akaike information criterion (AIC) and Harrell's C tests. Results: After assessing for discriminative ability, the linear trend of log MTR surpassed those of resection margin and tumour thickness in chi‐square, AIC and Harrell's C tests for the advanced pathologic T (pT) category. A multivariate Cox proportional hazard regression model revealed that log MTR <33% was associated with less favourable 5‐year disease‐specific survival (DSS) (P = 0.006) in the entire oral cancer study cohort. Other significant factors included perineural invasion (P = 0.021), pT category, (P = 0.005), pathologic N category (P < 0.001) and differentiation category (P = 0.022). Conclusions: Log MTR < 33% may be a predictor of less favourable outcome in the DSS of OSCC. Log MTR outperformed both resection margin and tumour thickness alone in terms of discriminative analysis. Our study could help in presurgical planning for high‐risk patients and in aiding the decision‐making process for adjuvant treatment. [ABSTRACT FROM AUTHOR]

Objective: Several comorbid measures have been developed and demonstrated the predictive ability for cancer mortality. We conducted a retrospective study on oral squamous cell carcinoma (OSCC) patients to compare the Charlson comorbidity index score (CCIS) to the Elixhauser comorbidity index score (ECIS).Methods: Newly diagnosed OSCC patients (n=232) post major surgery with or without adjuvant therapy were identified from the cancer registry database between 2006 and 2011. Comorbidities present prior to the cancer diagnosis were obtained and adapted to the CCIS and ECIS. The prevalence of comorbid conditions and the influence on disease-specific survival (DSS) rate were calculated and analyzed by Cox regression model. The discriminatory ability of these two comorbid measures was evaluated by using the adjusted hazard ratio and Akaike information criterion (AIC) in a multivariate regression model. The prediction accuracy was assessed using Harrell's c-statistic.Results: Most of the patients (93.5%) were male with a mean age of 54 ± 11 years and 77 of them (33.1%) had at least one comorbid condition. The ECIS was associated DSS, with an additional 10% increased risk observed for mortality for each increased score (HR, 1.10; 95% confidence interval [CI], 1.03-1.18) after adjusting with pathological risk features. However, the CCIS was not an independent prognostic factor for these patients. The ECIS increased discriminatory ability but the CCIS did not improve discrimination.Conclusions: Comorbid conditions significantly influenced the clinical outcomes of patient with OSCC post major surgery. A higher ECIS was associated with worse disease specific survival indicative of a valuable prognostic indicator. The ECIS may be considered in further clinical trials for a variety of cancers, including head and neck cancers. [ABSTRACT FROM AUTHOR]

DNA hypermethylation of promoter CpG islands is associated with epigenetic silencing of tumor suppressor genes in oral squamous cell carcinomas (OSCCs). We used a methyl-CpG-binding domain protein capture method coupled with next-generation sequencing (MBDCap-seq) to survey global DNA methylation patterns in OSCCs with and without nodal metastasis and normal mucosa (total n = 58). Of 1462 differentially methylated CpG islands identified in OSCCs relative to normal controls, MBDCap-seq profiling uncovered 359 loci linked to lymph node metastasis. Interactive network analysis revealed a subset of these loci (n = 23), including the anaplastic lymphoma kinase (ALK) gene, are potential regulators and effectors of invasiveness and metastatic progression. Promoter methylation of ALK was preferentially observed in OSCCs without node metastasis, whereas relatively lower methylation levels were present in metastatic tumors, implicating an active state of ALK transcription in the latter group. The OSCC cell line, SCC4, displayed reduced ALK expression that corresponded to extensive promoter CpG island methylation. SCC4 treatment with demethylating agents induced ALK expression and increased invasion and migration characteristics. Inhibition of ALK activity in OSCC cells with high ALK expression (CAL27, HSC3 and SCC25), decreased cell growth and resulted in changes in invasive potential and mesenchymal marker expression that were cell-line dependent. Although ALK is susceptible to epigenetic silencing during oral tumorigenesis, overwriting this default state may be necessary for modulating invasive processes involved in nodal metastases. Given the complex response of OSCC cells to ALK inhibition, future studies are required to assess the feasibility of targeting ALK to treat invasive OSCCs. [ABSTRACT FROM AUTHOR]