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Background: This study aimed to establish a simple predictive model for oropharyngeal cancer (OPC) in an area with a relatively low prevalence of human papillomavirus (HPV) and frequent betel nut chewing. Methods: A total of 116 patients with OPC were recruited from the clinical research database of a referral cancer center between 2013 and 2018. Patient characteristics—including age, gender, tumor stage, differentiation, and treatment modality—were extracted from the database. Patients diagnosed after 2018 were staged using the 7th AJCC staging system to explore the impact of extra-nodal tumor extension (ENE) on survival. Immunohistochemical analysis was performed for p16, epidermal growth factor receptor (EGFR), p53, and programmed cell death ligand 1 (PD-L1). ENE status was evaluated by pathological analysis or radiological features. Primary outcome was disease-specific overall survival (OS). Univariate and multivariate Cox regression were used to establish a predictive model. Results: Mean age was 57.3 ± 9.9 years; 103 patients (88.8%) were male. P16 positive OPC was positively associated with higher PD-L1 and a tonsillar sub-site and negatively associated with betel nut chewing and cigarette smoking. In Cox regression, age, p16 status, EGFR, cT4, ENE, and cigarette smoking were significantly associated with OS. In survival tree analysis, cT stage was the most important risk stratification parameter, followed by EGFR expression and p16 status. Patients with cT4 stage or high EGFR were classified as the high-risk group and had poorest OS. Conclusions: Due to the low prevalence of HPV and popularity of betel nut chewing in Asia, the relative importance of prognostic predictors for OPC are not identical to Western countries. Identification of significant prognostic biomarkers may improve treatment. Trial registration This study was registered and approved by the Institutional Review Board (IRB) of Kaohsiung Veterans General Hospital (VGHKS19-CT9-07; date of approval: Aug 9, 2019). [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]

Background: The purpose of this study was to determine failure patterns and clinicopathologic prognostic factors in patients with locally advanced buccal cancer after postoperative intensity‐modulated radiotherapy (IMRT). Methods: Eighty‐two patients with locally advanced (American Joint Committee on Cancer [AJCC] stage III/IV) buccal cancer who underwent surgery followed by postoperative IMRT between January 2007 and October 2012 were retrospectively analyzed. Results: Eighteen patients had local recurrences as the first recurrent site and 11 had supramandibular notch recurrences; the majority of recurrences were classified as marginal failures. The median time from the first local or regional recurrence to death was 5.9 months. In multivariate analyses of survivals, the initial masticator space involvement was the most important prognostic factor. Masticator space involvement, N classification, and maxillectomy were the significant prognostic predictors for supramandibular notch recurrences. Conclusion: Postoperative IMRT for buccal cancer should not include the surgical beds alone, rather, it should be based on the potential patterns of spread. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models. Methods: We isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression. Results: Combination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells. Conclusions: These findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Identification of patients at risk of death from cancer surgery should aid in preoperative preparation. The purpose of this study is to assess and adjust the age-adjusted Charlson comorbidity index (ACCI) to identify cancer patients with increased risk of perioperative mortality. Methods: We identified 156,151 patients undergoing surgery for one of the ten common cancers between 2007 and 2011 in the Taiwan National Health Insurance Research Database. Half of the patients were randomly selected, and a multivariate logistic regression analysis was used to develop an adjusted-ACCI score for estimating the risk of 90-day mortality by variables from the original ACCI. The score was validated. The association between the score and perioperative mortality was analyzed. Results: The adjusted-ACCI score yield a better discrimination on mortality after cancer surgery than the original ACCI score, with c-statics of 0.75 versus 0.71. Over 80 years of age, 70–80 years, and renal disease had the strongest impact on mortality, hazard ratios 8.40, 3.63, and 3.09 (P < 0.001), respectively. The overall 90-day mortality rates in the entire cohort varied from 0.9%, 2.9%, 7.0%, and 13.2% in four risk groups stratifying by the adjusted-ACCI score; the adjusted hazard ratio for score 4–7, 8–11, and ≥ 12 was 2.84, 6.07, and 11.17 (P < 0.001), respectively, in 90-day mortality compared to score 0–3. Conclusions: The adjusted-ACCI score helps to identify patients with a higher risk of 90-day mortality after cancer surgery. It might be particularly helpful for preoperative evaluation of patients over 80 years of age. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the impact of comorbidity on survival outcomes for patients with nasopharyngeal carcinoma (NPC) post radiotherapy (RT). Methods: A total of 4095 patients with NPC treated by RT or RT plus chemotherapy (CT) in the period from 2007 to 2011 were included through Taiwan’s National Health Insurance Research Database. Information on comorbidity present prior to the NPC diagnosis was obtained and adapted to the Charlson Comorbidity Index (CCI), Age-Adjusted Charlson Comorbidity Index (ACCI) and a revised head and neck comorbidity index (HN-CCI). The prevalence of comorbidity and the influence on survival were calculated and analyzed. Results: Most of the patients (75%) were male (age 51±13 years) and 2470 of them (60%) had at least one comorbid condition. The most common comorbid condition was diabetes mellitus. According to these three different comorbidity index (CCI, ACCI and HN-CCI), higher scores were associated with worse overall survival (P< 0.001). The Receiver Operating Characteristic (ROC) curve was used to assess the discriminating ability of CCI, AACI and HN-CCI scores and it demonstrated the predictive ability for mortality with the ACCI (0.693, 95% CI 0.670–0.715) was superior to that of the CCI (0.619, 95% CI 0.593–0.644) and HN-CCI (0.545, 95%CI 0.519–0.570). Conclusion: Comorbidities greatly influenced the clinical presentations, therapeutic interventions, and outcomes of patients with NPC post RT. Higher comorbidity index scores accurately was associated with worse survival. The ACCI seems to be a more appropriate prognostic indicator and should be considered in further clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy with or without chemotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC). It wastes time from diagnosis to treatment. Treatment time of radiotherapy generally takes at least seven weeks. The current study aimed to evaluate factors associated with prolonged wait time and longer duration of radiotherapy in NPC patients. Methods and Materials: From Taiwan's National Health Insurance research database, we identified 3,605 NPC patients treated with radiotherapy between 2008 and 2011. Wait time was calculated from the date of diagnosis to the start of radiotherapy. The impact of each variable on wait time and duration of radiotherapy was examined by multilevel analysis using a random-intercept model. Results: The mean wait time and duration of radiotherapy were 1.78±3.33 and 9.72±7.27 weeks, respectively. Multilevel analysis revealed prolonged wait time in patients aged 45–65 years, those receiving radiotherapy alone, those with more comorbidities, those with low SES, and those living in eastern Taiwan. A prolonged duration of radiotherapy was associated with receipt of concurrent chemoradiotherapy, more comorbidities, and moderate SES. Conclusions: Understanding the factors associated with longer wait times and duration of radiotherapy in patients with NPC may help healthcare providers better assist both these patients and potentially those with other head-and-neck cancers. [ABSTRACT FROM AUTHOR]