Improving accuracy in nodal staging of oral cancer: Proposal of a new system.

BACKGROUND: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. 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) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. RESULTS: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. CONCLUSION: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

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.

Reconstruction in Salvage Surgery for Head and Neck Cancers.

Introduction: Salvage surgery is the treatment option in recurrences and second primary tumors. This paper aimed to study the options and outcomes of reconstruction and the predictors of poor reconstructive outcomes in salvage surgery for head and neck cancers. Study Design: This is a retrospective study of all patients who underwent reconstructive flap surgery as part of salvage surgery for head and neck cancers between the years 2004 and 2017. Methods: The initial treatment may be single modality radiotherapy or surgery or multimodality with combinations of surgery, radiotherapy, and chemotherapy. Any pathology that required surgical salvage was included. Any procedures done purely as reconstructive surgery were excluded. Predictor variables included demographical, clinical, and treatment factors. The outcome parameter was the occurrence of any flap-related complication or not. The complications and morbidity related to the procedures are reported. Results: Ninety-three patients underwent loco-regional flaps (LRF group), and 100 had free flaps (FF group). Pectoralis major flap was the commonest flap used in 68 patients (73.1%). Anterolateral thigh (ALT) flap was the commonest free flap and comprised 41% of the FF group. Any skin-related complication was seen in 35 patients (37.6%) and 41 (41%), respectively, in LRF and FF subsets. Any flap-related complication was seen in 16 patients (17.2%) and 29 patients (29%), respectively, in LRF and FF subsets. A summary measure "any one of the complications" was seen in 46 (49.5%) and 57 (57%), respectively, in LRF and FF subsets. Univariate and multivariate analysis for any flap-related complication identified no statistically significant predictor. Conclusions: Soft tissue flaps were preferred in salvage reconstruction, though the defects had a bony component. In the microvascular free flap reconstruction era, pectoralis major flap has shifted its role from a "workhorse flap" to a "salvage flap." About half of the patients develop some complications. Flap-related complications are also common. In salvage surgery, it is important that an appropriate flap is selected, suitable for the setting, according to the indications, neck, and patient conditions.

Tobacco use and its impact on survival in young patients with oral cancer.

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.

Primary Tumor Staging for Oral Cancer and a Proposed Modification Incorporating Perineural Invasion: An International Multicenter Study.

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.

Advances and Controversies in the Management of Osteoradionecrosis After Head and Neck Cancer Treatment: A Narrative Review.

Osteoradionecrosis (ORN) is a painful and debilitating serious late complication following treatment for head and neck cancer (HNC) often requiring surgical resection of the jaw and complex multidisciplinary management. An important aggravating factor for mandibular ORN is surgical trauma, commonly dental extractions or implant placement following head and neck radiotherapy. The evidence on the treatment protocols ranges from conservative management to more radical surgical strategies including the use of hyperbaric oxygen therapy. The available evidence on the preventive approaches for ORN includes prophylactic dental care prior to radiotherapy, the use of hyperbaric oxygen (HBO) treatment and prophylactic antibiotics for post-radiotherapy extractions. However, the efficacy of hyperbaric oxygen therapy has been questioned recently signifying poor understanding of the pathophysiology of the condition and therapies targeting the fibroatrophic process have become a focus of ORN treatment. Implementing recent IMRT radiation techniques has also shown evidence to reduce the incidence of ORN. This review provides an insight into the variations in definition and classification of the ORN, the controversies in its pathophysiology and the advances in the prevention and management.

Oncological outcomes of compartmental surgery and wide local excision in oral tongue and floor of the mouth cancer.

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.

Risk Stratification in Oral Cancer: A Novel Approach.

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.

Incorporation of adverse features in advanced oral cancer improves precision in staging and patient prognostication.

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.

Mapping of head and neck cancer patient concerns inventory scores on to Euroqol-Five Dimensions-Five Levels (EQ-5D-5L) health utility scores.

BACKGROUND: The purpose of this paper is to map the number of concerns on the dimensions in Head and Neck Patient Concerns Inventory (PCI) on to the health utility (HU) index scores on Euroqol-Five Dimensions-Five levels {EQ-5D-5L) . METHODS: This is a cross-sectional survey conducted in patients who have completed their treatment. Four candidate models were considered, three based on ordinary least squares regression (OLS) and one two-parts model. RESULTS: A reduced OLS model based on 'Physical and functional', 'Treatment-related', and 'Psychological, emotional and spiritual well-being' domains was found best on the estimation sample. This was validated externally on a separate sample. CONCLUSIONS: This is the first study that mapped a non-QOL tool to generate HU scores on EQ-5D-5L. The proposed mapping algorithm can estimate the cost-utility in economic evaluation studies when HU scores are not directly available. The algorithm will be best suited for studies in low-middle income countries.

Bilateral Microvascular Submandibular Gland Transfer with Implantation of Wharton's Duct in Superior Conjunctival Fornix: A Vision-Saving Procedure for Severe Dry Eye Disease.

Dry eye can initially cause mild symptoms of irritation and may rapidly progress to corneal scarring and blindness. Tear substitutes can only help for mild cases. With the advancement in microsurgical techniques, an option of transferring vascularized salivary glands has shown positive results. We present a case of a 5-year-old boy with congenital alacrimia with ocular surface damage. Vascularized autologous submandibular gland transfer was considered as a viable option for this patient. We performed the gland transfer in two separate stages for the two eyes (1 year 5 months apart). The patient was evaluated for up to 2 years for the right eye and for 7 months for the left eye. Dry eye workup showed drastic improvement (right > left). Biochemical analysis showed gradual transition to resemble that of natural tears. This procedure can result in significant symptomatic improvement and can be a promising treatment option for cases of severe dry eye.

Outcomes of Re-exploration Procedures After Head and Neck Free Flap Reconstruction.

This study was conducted to evaluate the outcomes of re-exploration procedures done after head and neck microvascular flap reconstructions. This is a retrospective review of 109 flaps in 106 patients (three patients had two flaps each) that underwent re-exploration procedures in 1001 consecutive free flap surgeries. The outcome was analysed in terms of the type of the flaps, re-exploration rate, flap salvage rate and overall flap success rate. Free radial forearm (RFF) was the commonest flap done (354, 35.3%). One hundred nine flaps underwent re-exploration procedures in 106 patients. Out of this, 79 flaps could be salvaged, and 30 flaps failed. There were also another ten flaps, which failed without any re-exploration. The overall re-exploration rate was 10.8%. The flap salvage rate was 72.4%. The overall flap success rate was 96.1%. Nearly three-fourths of the flaps with vascular compromise can be successfully salvaged with appropriate and timely intervention.

Cost-effectiveness of oral cancer screening approaches by visual examination: Systematic review.

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.

Low PDL1 Expression in Tumour Infiltrating Lymphocytes Predicts Local Recurrence in Oral Squamous Cell Carcinoma.

In oral squamous cell carcinoma (OSCC), expression of PDL1 is controversial with expressions showing a positive and negative correlation with survival in previous studies. Additionally, it is unclear whether expression on the tumour or tumour infiltrating lymphocytes (TIL) is a better predictor of survival. We performed this study on a cohort of Indian patients with OSCC to determine impact of PDL1 expression on survival. Retrospective analysis of 64 patients of OSCC treated with curative intent surgery with or without adjuvant therapy was performed. Stored tissue blocks were extracted and quantitative immunohistochemistry was performed for PDL1 expression separately on the tumour and the TIL using commercially available Dako kits. Correlation of clinical and pathological variables with PDL1 expression was performed using chi-square test. Survival analysis was performed using Kaplan-Meier method and Cox proportional hazards ratio. In our cohort, PDL1 expression was low, both in tumour (92% had <1% expression) and TIL (56% had <1% expression). Tumour low PDL1 expression (<1%) was associated with a higher risk of lymphovascular invasion (p = 0.044) and bone invasion (p = 0.01) but did not impact survival. Low TIL PDL1 expression (<1%) was more common in younger patients (<45 years) (p = 0.023) significantly predicting local recurrence (p = 0.02). PDL1 expression in OSCC was low. Low TIL PDL1 was common in younger patients and predicted local recurrence. Further study is required to better understand the relationship between age, tumour microenvironment and local recurrence.

Economic evaluations comparing Tran-oral robotic surgery and radiotherapy in oropharyngeal squamous cell carcinoma: A systematic review.

BACKGROUND: Trans-oral robotic surgery (TORS) and primary radiotherapy are the two modalities used to treat early T stage oropharyngeal squamous cell carcinoma(OPSCC). Prior literature including a recent randomized controlled trial have not shown the superiority of one modality over the other. When the modalities have similar outcomes, cost-effectiveness have an important role in deciding on the appropriate treatment. There are economic evaluations comparing the two modality with contradicting conclusions. The purpose of this review is to synthesise the evidence. METHODS: This is a systematic review of economic evaluations on the treatment modalities for OPSCC, namely TORS versus radiotherapy. The main outcome measures were the Cost-utility results reported as the effectiveness and costs separately and as part of the Incremental Cost-Effectiveness Ratio. RESULTS: Literature search identified five articles reporting cost-utility analysis, eligible for the review. A strategy is considered to be dominant when the effectiveness achieved was more at a lower cost, compared to the comparator. At the willingness to pay (WTP) threshold of 50,000 to 100,000 USD per Quality Adjusted Life-Year (QALY), three studies showed dominance of strategies in the base case analysis (TORS in two and Primary Chemoradiotherapy in one). Two of the articles studied node negative patients, one of them favored TORS. Three articles had node positive patients and two of them favored TORS and one favored chemoradiotherapy in the base case analysis. On sensitivity analysis, adjuvant treatment was found to be the detrimental factor affecting the cost-effectiveness. CONCLUSIONS: TORS can be considered a cost-effective strategy in early T stage OPSCC, if the addition of adjuvant therapy involving radiotherapy can be avoided. Literature have shown that around 70% of the early cancers would require adjuvant treatment. This implies the importance of case selection while considering TORS as the initial treatment modality.

Validation of an Intelligibility Assessment Tool in an Indian Language for Perceptual Speech Analysis in Oral Cancer Patients.

This study aimed to develop a speech intelligibility tool in Malayalam, an Indian language, based on the perceptual analysis. The tool had components of vowel, consonant, word, passage, and overall intelligibility. After face and content validation, a sample of 30 consecutive oral cancer patients underwent preliminary testing for internal consistency, inter- and intra-rater reliability, concurrent, and known-group validity. Subsequent validation was done in 80 T1-T4 patients from two centers. The scale had a high level of internal consistency; the Cronbach's alpha was 0.847 and good intra-rater and inter-rater agreement amongst all raters. There was a strong correlation between the Malayalam and the English passage. Pearson correlation coefficient of 0.646 proved concurrent validity. On known-group and subsequent validation, the tool showed expected differences between the treatment groups. The speech tool proved to be reliable and valid for perceptual evaluation of speech intelligibility in oral cancer patients.

Metrics of pN-staging in oral squamous cell carcinoma: An analysis of 1,905 patients.

BACKGROUND: We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. METHODS: Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N+. Overall survival probabilities were summarised with the Kaplan-Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores. RESULTS: All 1,905 included patients were classified according to TNM7 and pN-N+. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N+ ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N+, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival. CONCLUSIONS: The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N+ conveyed the best measures of prognosis and should be considered in future TNM iterations.

Predictive nomograms for oral tongue squamous cell carcinoma applying the American Joint Committee on Cancer/Union Internationale Contre le Cancer 8th edition staging system.

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.

Effect of age and gender in non-smokers with oral squamous cell carcinoma: Multi-institutional study.

BACKGROUND: In developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct cohort with different prognosis. A recent analysis found that elderly non-smoking females with OSCC had significantly worse prognosis, concluding that this was a distinct patient population with poorer survival. The primary aim of this study was to determine the effect of gender and age on prognosis in OSCC, and the interaction between these two variables. METHODS: Multinational multi-institutional data were collected from six sites. The primary outcome of interest was disease specific survival (DSS). Time to local, regional, and distant recurrence were investigated as secondary outcomes. RESULTS: 3379 patients with OSCC were included. Males had significantly worse DSS compared to females (HR 1.24, 95% CI 1.08-1.43, p = 0.003). Females <70 years of age had significantly better DSS compared to females ≥70 years of age (HR 0.69, 95% CI 0.51-0.94, p < 0.001) but elderly females had similar DSS to males, regardless of age. When age was divided into three groups, the middle-aged group (45-69 years) had a significantly better DSS compared to elderly patients (HR 0.87, 95%CI 0.78-0.96, p < 0.001), however younger patients had similar DSS to elderly patients. When the effect of age (young v middle v elderly) was compared in each gender, young and middle-aged females had the most favourable DSS (log-rank p < 0.001). Middle-aged females who smoked had a 10% survival advantage compared to middle-aged males that smoked at five years. CONCLUSIONS: Age, gender, tumour subsite, and smoking status are important drivers of survival in OSCC. However, gender appears to be the most important predictor with young and middle-aged females having the most favourable prognosis.

Young age is not a predictor of disease specific survival in oral cancer: A multi-institutional study.

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.