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Objective: To explore the impact of textbook outcome (TO) on long‐term survival in oral cancer surgery. Subjects and Methods: In total, 386 patients with tumor resection, neck dissection (ND), and reconstruction between 2011 and 2020 were included. TO was defined as negative margin; adequate ND; no 3‐day emergency room revisit; no 30‐day readmission; and length of stay ≤22 days. Multivariate Cox regression was used to evaluate the impact of TO and 5‐year overall survival (OS). Results: The TO rate was 35%. Younger age, subsite in buccal area, Charlson Comorbidity Index Score of 0, higher body mass index, higher hemoglobin, higher albumin, and unilateral ND were associated with TO. 5‐year OS was 70.5% in overall TO patients and 49.0% in non‐TO patients (HR, 0.47; 95% CI, 0.31–0.70; p < 0.001). Non‐TO was associated with an increased mortality rate (aHR, 1.73; 95% CI, 1.14–2.63) after adjusting other factors and the result remained robust with inverse probability of treatment weighting analysis. The impact of TO on OS was more significant in age <60, advanced stage, and diagnosis year before 2018. Conclusion: Not achieving TO in oral cancer surgery was associated with worse long‐term outcome. TO could be used as a proxy for surgical quality improvement. [ABSTRACT FROM AUTHOR]

Objective: In Taiwan, the median age of diagnosis for oral cavity cancer is 51 year old, which is about 10 years earlier than that in Western countries. A recent study assessing the effect of marriage on outcomes for elderly oral cavity cancer patients (≥66 years old) showed that marriage was associated with better survival. However, little is known about the prognostic significance of marital status in oral cavity cancer patients aged 65 years and younger.Methods: Data from 2007 to 2014 were collected from the Cancer Registry Dataset of the Kaohsiung Veterans General Hospital. We reviewed the records of all newly diagnosed patients with oral cavity cancer who were aged 65 years and younger and being treated by primary surgery with or without neck dissection or adjuvant therapy. None of the included patients had distant metastasis upon diagnosis. In total, 457 patients were indentified. We used multivariate Cox regression model to evaluate the effect of marriage on disease-specific survival rates after adjusting for demographic variables and treatments.Results: There was no significant difference between the married and unmarried groups in stage at diagnosis or treatment. The 5-year disease-specific survival was 70.9% in the married group and 51.2% in the unmarried group (P=0.001). Multivariate analysis with Cox regression showed that unmarried patients had worse disease-specific survival (unmarried, adjusted hazard ratio [aHR] 1.51, 95% CI: 1.06-2.16). Subgroup analysis among patients stratified by the independent factors in multivariate analysis revealed that being unmarried was associated with a trend of worse survival in most stratified groups.Conclusion: Marriage was associated with better disease-specific survival for oral cavity cancer patients aged 65 years and younger. [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]

Summary: This population-based study investigated the relationship between individual and neighborhood socioeconomic status (SES) and oral cancer mortality. A population-based follow-up study was conducted of 3607 oral cancer patients (predominantly male) who were diagnosed between 2004 and 2005. Each patient was traced to death or for 2years. Individual SES was defined by enrollee category. Neighborhood SES was defined by income, and numbers of doctors, and neighborhoods were grouped into advantaged and disadvantaged areas. The Cox proportional hazards model was used to compare the death-free survival rate between the different SES groups after adjusting for possible confounding and risk factors. In oral cancer patients aged below 65years, death rates among those with low SES were highest in disadvantaged neighborhoods. After adjusting for patient characteristics (age, gender, Charlson Comorbidity Index Score, urbanization, and area of residence), tumor extent, treatment modalities (operation, adjuvant therapy), hospital characteristics (ownership, teaching level, caseload), and year of diagnosis, oral cancer patients with low individual SES in disadvantaged neighborhoods conferred a 1.46- to 1.64-fold higher risk for death, compared with patients with high individual SES in advantaged neighborhoods. No statistically significant difference was found in risk of death between different SES groups in patients aged 65 and above. Our findings indicate that oral cancer patients with low individual SES have the highest risk of mortality even under a universal health-care system. Public health strategies and welfare policies must continue to focus on this vulnerable group. [Copyright &y& Elsevier]

Summary: Patients with oral cancer utilize considerable health care resources, particularly when wide resection of the tumor and reconstruction with pedicle flap/free flap is performed. This study was conducted to explore the relationship between survival rates and surgeon volume. A total of 1256 patients who underwent resections for oral cancer in 2005 were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional regression model, and propensity score were used to evaluate the association between 3-year survival rates and surgeon caseloads. Oral cancer patients treated by high-volume surgeons (caseload 22–117) had better survival rates (hazard ratio [HR]=0.656; 95% confidence interval [CI], 0.484–0.89; P =0.007) using the Cox proportional regression model after adjusting for patients’ comorbid conditions, hospital, and surgeon characteristics. When analyzed by propensity score, the adjusted 3-year survival rate was 74% for patients treated by high-volume surgeons compared to 58% in the low/medium-volume group (P =0.019). We concluded that for patients who underwent oral cancer resection and reconstruction, after adjusting for differences in the case mix, high-volume surgeons had better 3-year survival rates. Treatment strategies adopted by high-volume surgeons should be analyzed further and utilized more widely. [Copyright &y& Elsevier]

Background: To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection.Methods: In the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection.Results: Of the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men, and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49-0.84) in those with < 18 lymph nodes (LNs) removed, but not in those with 19-24 LNs removed (aHR 0.78; 95% CI 0.73-1.13), and in those with ≥ 25 LNs removed (aHR 0.96; 95% CI 0.75-1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45-0.97) in those with < 18 LNs. The protective effect was not seen in those with 18-24 LNs (aHR 1.07; 95% CI 0.59-1.96), and in those with ≥ 25 LNs (aHR 1.12; 95% CI 0.81-1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with < 18 LNs removed.Conclusion: Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection. [ABSTRACT FROM AUTHOR]

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]

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]

Background: Hepatoma-derived growth factor (HDGF) participates in angiogenesis and represents a negative prognostic factor in oral cancer. The current study was designed to elucidate the regulatory mechanism between HDGF and vascular endothelial growth factor (VEGF) and the clinical impact of oral cancer.Methods: TCGA data and surgical samples from oral cancer patients were used for the clinicopathological parameter and survival analysis. Human oral cancer SCC4 and SAS cells were treated with recombinant HDGF protein. VEGF gene expression and protein level were analyzed by RT-PCR, Western blotting, and enzyme-linked immunosorbent assay. The signaling pathways for regulating VEGF expression were investigated. The nucleolin neutralizing antibody and HIF-1α inhibitor were applied to SCC4 cells to investigate their effects on the HDGF-stimulated VEGF pathways.Results: TCGA and immunohistochemical analysis revealed a positive correlation between HDGF and VEGF expression in oral cancer tissues. Recombinant HDGF significantly increased VEGF gene and protein expression in oral cancer SCC4 cells in a dose-dependent manner. HDGF enhanced the phosphorylation levels of AKT and IkB and the protein level of HIF-1α and NF-κB. The nucleolin-neutralizing antibody abolished HDGF-stimulated HIF-1α, NF-κB and VEGF protein expression in SCC4 cells. The HIF-1α inhibitor antagonized the HDGF-induced VEGF gene expression. High VEGF expression was strongly correlated with HDGF expression, advanced disease, and poor survival.Conclusion: This study postulated a new pathway in which HDGF activated HIF-1α and then induced VEGF expression through binding to membrane nucleolin under normoxic conditions, leading to poor disease control. The HDGF/HIF-1α/VEGF axis is important for developing future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background:Oral cancer leads to a considerable use of health care resources. Wide resection of the tumor and reconstruction with a pedicle flap/ free flap is widely used. This study was conducted to investigate if young age at the time of diagnosis of oral cancer requiring this treatment confers a worse prognosis. Methods:A total of 2339 patients who underwent resections for oral cancer from 2004 to 2005 were identified from The Taiwan National Health Insurance Research Database. Survival analysis, Cox proportional regression model, propensity scores, and sensitivity test were used to evaluate the association between 5-year survival rates and age. Results:In the Cox proportional regression model, the older age group (>65 years) had the worst survival rate (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.45-2.22; P<0.001). When analyzed using the propensity scores, the adjusted 5-year survival rates were also poorer for oral cancer patients with older age (>65 years), compared to those with younger age (<45 years) (P<0.001). In sensitivity test, the adjusted hazard ratio remained no statistically elevated in the younger age group (<45 years). Conclusions:For those oral cancer patients who underwent wide excision and reconstruction, young age did not confer a worse prognosis using a Cox proportional regression model, propensity scores or sensitivity test. Young oral cancer patients may be treated using general guidelines and do not require more aggressive treatment. [ABSTRACT FROM AUTHOR]