Search

Objectives: The incidence of young‐onset oral squamous cell carcinoma (OSCC) is growing, even among non‐smokers/drinkers. The effects of adverse histopathological features on long‐term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio‐economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. Materials and Methods: Four hundred and seventy‐eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan–Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population‐level data. Results: Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5‐year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. Conclusion: Young‐onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio‐economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC. [ABSTRACT FROM AUTHOR]

The objective of this study is to determine if the incorporation of perineural invasion (PNI) into the T‐classification would improve the prognostic performance of TNM‐8. An international, multicenter study of 1049 patients with oral cavity squamous cell carcinoma that were treated from 1994 to 2018 is performed. Various classification models are developed within each T‐category and evaluated using the Harrel‐concordance index (C‐index), Akaike‐information criterion (AIC), and visual inspection. Stratification into distinct prognostic categories, with internal validation, is performed using bootstrapping analysis (SPSS and R‐software). Through multivariate analysis, PNI is significantly associated with disease‐specific survival (p < 0.001). PNI integration into the staging system results in a significantly improved model compared with the current T category alone (lower AIC, p < 0.001). The PNI‐integrated model is superior in predicting differential outcomes between T3 and T4 patients. A new model for T‐classification of oral cavity squamous cell carcinoma is proposed, which is based on incorporating PNI into the staging system. These data can be used for future evaluations of the TNM staging system. [ABSTRACT FROM AUTHOR]

Background: Tobacco is a major risk factor associaetd with developing oral factor. Recent studies have shown that the age of onset, especially in Asia, is reducing. This study was to determine if tobacco exposure correlated with prognosis in oral squamous cell carcinoms (OSCC) based on age at diagnosis. Methods: Six hundred and forty three patients of OSCC treated in our institution were divided into four groups, younger patients (<45 years) with or without tobacco exposure and older patients (>45 years) with or without tobacco exposure, and compared with respect to prognostically relevant variables, disease-free survival (DFS) and overall survival (OS). Survival analysis was performed. Results: The percentage of those with tobacco exposure was comparable in both age groups. Tobacco correlated with known pathological determinants in OSCC; however, perineural invasion, lymphovascular invasion, and extranodal extension were significantly more common in the young. On survival analysis, tobacco exposure impacted OS (P = 0.04) and DFS (P = 0.03) in patients <45 years, and not in older patients >45 years. On multivariate analysis, tobacco exposure in the young was significantly associated with recurrence (P = 0.03, hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.07--2.94) but not survival. Conclusion: Younger patients with a history of tobacco use have a significantly higher risk of recurrence and mortality due to OSCC, but this difference could not be attributed to any of the known prognostic determinants in OSCC. Younger patients also had more adverse pathological features. Whether this occurs because of altered disease biology or pathways of carcinogenesis in the young with tobacco exposure is unknown. Younger tobacco users with oral cancer are more likely to have a poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) Is a common head and neck cancer with high morbidity and mortality. Currently, treatment decisions are guided by TNM staging, which omits important negative prognosticators such as lymphovascular invasion, perineural invasion (PNI), and histologic differentiation. We proposed nomogram models based on adverse pathological features to identify candidates suitable for treatment escalation within each risk group according to the National Comprehensive Cancer Network (NCCN) guidelines. Methods: Anonymized clinicopathologic data of OSCC patients from 5 tertiary healthcare institutions in Asia were divided into 3 risk groups according to the NCCN guidelines. Within each risk group, nomograms were built to predict overall survival based on histologic differentiation, histologic margin involvement, depth of invasion (DOI), extranodal extension, PNI, lymphovascular, and bone invasion. Nomograms were internally validated with precision-recall analysis and the Kaplan-Meier survival analysis. Results: Low-risk patients with positive pathological nodal involvement and/or positive PNI should be considered for adjuvant radiotherapy. Intermediate-risk patients with gross bone invasion may benefit from concurrent chemotherapy. High-risk patients with positive margins, high DOI, and a high composite score of histologic differentiation, PNI, and the American Joint Committee on Cancer (AJCC) 8th edition T staging should be considered for treatment escalation to experimental therapies in clinical trials. Conclusion: Nomograms built based on prognostic adverse pathological features can be used within each NCCN risk group to fine-tune treatment decisions for OSCC patients. [ABSTRACT FROM AUTHOR]

Background: Despite revised staging criteria, stratification of patients with advanced oral squamous cell carcinoma (OSCC) remains difficult. Well‐established features like perineural invasion (PNI), differentiation, and lymphovascular‐invasion (LVI) are controversial, and hence omitted from staging. We endeavor to better stratify this cohort by identifying predictors of survival in advanced OSCC (T3‐4). Methods: Seven hundred and forty‐two patients with T3‐4 OSCC underwent surgery from 2006 to 2013. Cox regression was performed to determine predictors of overall survival (OS). Results: OS was adversely impacted by PNI (p = 0.046), LVI (p = 0.038), moderate/poor differentiation (p = 0.001), close/involved surgical margins (p = 0.002), pT (p = 0.034), and pN (p < 0.001). The cumulative number of adverse histopathological features predicted poorer OS; HR 2.64 (CI 1.42–4.90) for one adverse feature and HR 4.23 (CI 2.34–7.67) for ≥2. Conclusion: In advanced OSCC, stratification with histopathologic risk factors can predict survival even in maximally treated patients; adjuvant therapies are unable to entirely mitigate this risk. Incorporation of adverse features into future editions of TNM can improve precision in staging and identify candidates for treatment escalation. [ABSTRACT FROM AUTHOR]

The present study is the first systematic review of papers that have performed a full economic evaluation on oral cancer screening strategies using visual oral examination. The review questions were (1) Is screening a cost‐effective strategy in oral cancer? (2) What is the most cost‐effective strategy among the different screening approaches in oral cancer? The main outcome measure was the incremental cost‐effectiveness ratio. The study identifies and reviews seven full economic evaluations. The included studies scored 75%–100% on the methodological appraisal. Majority of the studies reports that oral cancer screening is a cost‐effective strategy, especially in an opportunistic setting and high‐risk subset of patients. The results were sensitive to cost and effectiveness parameters. Oral cancer screening, though found cost‐effective, the uncertainty around these parameters necessitates additional studies that include better estimates in the modeling assessments. The heterogeneity in studies limited comparison and generalization. [ABSTRACT FROM AUTHOR]

Background: Nomograms applying the 8th edition of the TNM staging system aimed at predicting overall (OS), disease‐specific (DSS), locoregional recurrence‐free (LRRFS) and distant recurrence‐free survivals (DRFS) for oral tongue squamous cell carcinoma (OTSCC) are still lacking. Methods: A training cohort of 438 patients with OTSCC was retrospectively enrolled from a single institution. An external validation set of 287 patients was retrieved from two independent institutions. Results: Internal validation of the multivariable models for OS, DSS, DRFS and LRRFS showed a good calibration and discrimination results with optimism‐corrected c‐indices of 0.74, 0.75, 0.77 and 0.70, respectively. The external validation confirmed the good performance of OS, DSS and DRFS models (c‐index 0.73 and 0.77, and 0.73, respectively) and a fair performance of the LRRFS model (c‐index 0.58). Conclusions: The nomograms herein presented can be implemented as useful tools for prediction of OS, DSS, DRFS and LRRFS in OTSCC. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to evaluate the oncological outcomes of salvage surgery in squamous cell carcinoma of the head and neck (SCCHN). Methods: This is a retrospective analysis of all patients of SCCHN with recurrence or second primary, post‐treatment, who underwent salvage surgery. The outcomes were analyzed in terms of overall survival, overall survival postsalvage surgery and disease‐free survival (DFS) postsalvage surgery. Clinical and pathological predictors were considered. Results: Two hundred and forty‐one patients were included. The mean follow‐up was 56.33 months. Five‐year survival OS from date of initial diagnosis of the tumor was 61.2%. The 5‐year OS survival after salvage surgery was 47.1%. Five‐year DFS after salvage surgery was 28.1%. Prior chemoradiotherapy and pathological perineural invasion were independent predictors on multivariate analysis. Conclusions: Survival outcomes after appropriate salvage treatment are good. Prior chemoradiotherapy and perineural invasion on salvage pathology are predictors of poorer outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The 8th edition of the AJCC has introduced a new nodal staging system for head and neck cancers. Alternate nodal staging systems exist, however they have not been compared to the current AJCC staging system.Materials and Methods: A retrospective analysis of 643 patients with oral squamous cell carcinoma (OSCC) treated with surgery ± adjuvant therapy in a single institution between 2004 and 2014 was undertaken. Nodal staging was performed using AJCC 8th edition (AJCC8), number of positive lymph nodes (PN), log odds of positive lymph nodes (LODDS) and lymph node ratio (LNR). Survival analyses for disease free survival (DFS) and overall survival (OS) were performed with the different staging systems and they were compared on the basis of hazard consistency, hazard discrimination, explained variation and likelihood difference.Results: Overall, PN and LNR best predicted OS and DFS in our cohort of patients. AJCC8 had poor discrimination between sub-stages of pN2.Conclusion: PN and LNR provided the most accurate prediction of OS and DFS for patients with OSCC. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the factors affecting local control in patients with T1N0 squamous cell carcinoma (SCC) of the tongue. Methods: We conducted a retrospective analysis of 144 patients with pT1N0 SCC of the tongue who underwent wide excision and neck dissection without adjuvant therapy. Results: The adverse pathological features associated with local control were least margin 5 mm (P =.004), infiltrative margin (P =.403), depth >4 mm (P =.136), lymphovascular invasion (P =.301), and perineural invasion (P =.342). We derived a scoring system of 10 points based on the hazard ratio for local failure; those with scores >5 points had a 5‐year local control of <60%. Conclusion: This study suggests patients having a margin of 5 mm need revision, however, if they do not have additional adverse pathological features (score ≤4), local control is 88% at 5 years, and they may be observed. Those who have margins over 5 mm with a total score >5 may still benefit from adjuvant therapy. Those with margins over 5 mm have improved local control (P =.029). [ABSTRACT FROM AUTHOR]

Background: The American Joint Committee on Cancer (AJCC) eighth edition has incorporated depth of invasion into TNM classification of oral cavity squamous cell carcinoma (SCC) due to the prognostic impact on recurrence and survival. After reclassifying our patients with T1 to T2 oral cavity SCC according to these recommendations, we intended to study the effect of adverse pathological features (perineural invasion [PNI], lymphovascular invasion, and differentiation) on overall survival (OS). Methods: We conducted a retrospective analysis of 442 patients with T1 to T2 oral cavity SCC. Univariate and multivariate analysis was performed for impact of adverse pathological features on OS. Results: For the newly reclassified T1 to T2 oral cavity tumors, on multivariate analysis, the prognostically relevant parameters were PNI (P =.032) and differentiation (P =.009). Increasing adverse pathological features resulted in worse survival (P =.005). Conclusion: Incorporation of PNI and differentiation better reflect prognostic outcome in oral cavity tumors classified as T1 to T2 as per the new AJCC eighth edition. Increasing adverse pathological features resulted in worse survival. [ABSTRACT FROM AUTHOR]

Objectives: Oral tongue carcinomas represent more than half of the tumors arising in the oral cavity, a site with a high cancer specific mortality and impact on quality of life. Current guidelines are lacking for a standardized surgical approach of these tumors. The aim of this study is to compare two currently adopted surgical strategies, compartmental surgery (CTS) and wide local excision (WLE), with loco-regional control as the main oncological endpoint.Materials and Methods: An observational retrospective multicentric study was carried out enrolling a cohort of patients affected by oral tongue or floor of the mouth squamous cell carcinoma and surgically treated in 4 international tertiary referral centers. Survival analysis was performed by propensity-score matching approach and multivariable Cox regression analysis.Results: A cohort of 933 patients was enrolled. CTS was applied in 113 patients (12.1%) and WLE in 820 (87.9%). Analyzing a propensity-score matched cohort (98 CTS vs. 172 WLE) and applying a survival multivariable modeling strategy on the whole cohort, both confirmed that CTS and WLE are comparable and oncologically safe. Parameters such as number of positive lymph nodes, depth of invasion, and lymphovascular invasion still represent the key prognosticators.Conclusion: The main goals for surgical resection of oral cancer remain its three-dimensional circumferential clearance with adequate margins and en-bloc removal of the tumor-lymph node tract, independently of the technique adopted (CTS or WLE). Further prospective studies including quality of life evaluation are needed to better understand if one of these approaches can provide superior functional outcomes. [ABSTRACT FROM AUTHOR]

Background: Over the last few decades evidence has accumulated for increasing incidence of oral cavity squamous cell carcinoma (OSCC) in a younger cohort. Prior studies examining the effect of age at diagnosis on prognosis have produced conflicting data.Methods: A multi-institutional cohort study was performed across 6 different sites in Australia, Canada, India and Singapore. Disease-free (DFS), overall (OS) and disease-specific (DSS) survival were analysed. The association of the number of adverse features with survival outcomes was investigated.Results: From 3179 patients, age was a significant predictor of OS with patients older than 45 years having a 66% increased risk of death (HR 1.66, 95%CI 1.33 - 2.07, p < 0.001). The number of adverse features was a significant predictor of OS with 3 or more adverse features having a 199% increased risk (HR 2.99, 95%CI 2.61-3.43. p < 0.001). The estimate effect was greater in patients ≤ 45 years (HR 3.49 vs HR 2.81). Age was not a significant predictor of DSS with similar rates of death from OSCC in multivariable models. The number of adverse features was a significant predictor of DFS with ≥ 3 adverse features having a 140% increased risk of death. The number of adverse features was a significant predictor of DSS with ≥ 3 adverse features having a 230% increased risk of disease specific death.Conclusions: Age is not an independent predictor of disease specific mortality in OSCC. Differences in outcomes are due to the confounding effect of adverse clinicopathological features and the ability to tolerate surgery and adjuvant therapy. [ABSTRACT FROM AUTHOR]

Objectives: The AJCC 8th edition (AJCC 8) has introduced depth of invasion (DOI) and extranodal extension (ENE) into staging for oral squamous cell carcinoma (OSCC). Although validations have been performed on institutional datasets have shown a good performance, particularly in early OSCC, there have been no studies on diverse patient populations that determine the impact on prognostic heterogeneity.Materials and Methods: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery +/- adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) as endpoint, the prognostic performance of AJCC 7th and 8th editions were compared using Akaike Information Criterion (AIC), Bayesian Information Criteria (BIC), Harrell's concordance index (C-index).Results: When comparing AJCC 8 to AJCC 7, the heterogeneity in prediction of OS increased for T-category and N-category while remaining unchanged for TNM staging, suggesting AJCC 8 increased complexity with no improvement in predictive value. There were significant differences in median DOI and incidence of ENE between geographical regions, resulting in dissimilar rates of stage-migration when adopting AJCC 8.Conclusion: In an attempt to improve prognostic performance, AJCC 8 introduced more variables; however heterogeneity in these results in significant geographical differences in model discrimination and performance. Caution should be applied as this may result in inaccurate and unreliable prognostic predictions that may impact treatment recommendations. [ABSTRACT FROM AUTHOR]