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IMPORTANCE: Concurrent chemoradiotherapy delivers a high level of tumor control and survival benefits for patients with nasopharyngeal carcinoma (NPC). However, many uncertainties still exist regarding the outcomes of chemoradiotherapy, making a more precise survival prognostic system necessary. OBJECTIVE: To introduce a new staging system that combines tumor and clinical characteristics to improve the accuracy of prognosis for patients with NPC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study enrolled 207 patients with newly diagnosed NPC who underwent concurrent chemoradiotherapy between January 1, 2007, and December 31, 2014, at Chi-Mei Medical Center in Tainan, Taiwan. Data on these patients were collected from the cancer registry database of the Chi-Mei Medical Center. Patients who had a history of cancer or were unable to complete a full course of radiotherapy were excluded. Follow-up was completed on September 30, 2016, and the data analysis was performed from January 1, 2017, to February 28, 2017. MAIN OUTCOMES AND MEASURES: The risk factors associated with 5-year disease-specific survival were incorporated into the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer TNM staging system to construct a new prognostic staging system. The χ2 test for linear trend, the Akaike information criterion, and the C statistic were used to evaluate the monotonicity and discriminatory ability of the new prognostic staging system and the AJCC TNM staging system. RESULTS: Of the 207 patients enrolled in the study, 157 (75.8%) were men, and the mean (SD) age was 48 (11) years. Multivariate analysis identified advanced clinical T stage (adjusted hazard ratio [aHR], 3.20; 95% CI, 1.58-6.48), poor performance status (aHR, 2.62; 95% CI, 1.30-5.28), and cumulative cisplatin dose lower than 100 mg/m2 (aHR, 2.28; 95% CI, 1.10-4.74) as independent prognostic factors. The β coefficients from the Cox proportional hazards regression model were used to develop an integer-based, weighted point system; advanced clinical T stage, poor performance, and cumulative cisplatin dose lower than 100 mg/m2 were each assigned a score of 1. The sum of these risk scores was stratified into new stage I (score of 0), new stage II (score of 1), new stage III (score of 2), and new stage IV (score of 3). Compared with the AJCC TNM staging system, the new prognostic staging category had better monotonicity with a higher χ2 value (17.8 vs 25.6) for linear trend, better discriminatory ability with a smaller Akaike information criterion (367 vs 360), and a greater C statistic (0.702 vs 0.740) for 5-year disease-specific survival. CONCLUSIONS AND RELEVANCE: The new prognostic staging system has a better accuracy of prognosis of survival than the routinely used AJCC TNM staging system and thus is more useful in identifying high-risk patients for more intense treatment and care.

Nasopharyngeal carcinoma (NPC) is the most common malignant neoplasm of the nasopharynx. Despite improvements in the clinical treatment strategies for NPC, NPC patients usually have poor survival rates because of late diagnosis, tumor metastasis, and recurrence. Therefore, the identification of potential diagnostic and prognostic markers for NPC is imperative. We investigated the differential expression of cell adhesion-related genes (gene ontology:0003779) and tumorigenesis-related genes (GSE12452) in patients with NPC. The correlations between synaptopodin-2 (SYNPO2) immune expression and clinicopathological features were analyzed using Pearson chi-square test. Multivariate analysis was performed using Cox proportional hazards model. SYNPO2expression was significantly higher in NPC tumor tissues than in nontumor tissues. High SYNPO2expression was significantly associated with the advanced disease stage (P = .006). Univariate analysis showed that high expression of SYNPO2was associated with poor disease-specific survival, distal metastasis-free survival, and local recurrence-free survival in patients with NPC. Notably, our multivariate analysis demonstrated that high SYNPO2expression was substantially correlated with inferior disease-specific survival (hazard ratio = 1.968, P = .012) and local recurrence-free survival (hazard ratio = 3.386, P = .001). Overall, our findings reveal that SYNPO2may aid in the development of potential prognostic biomarkers for NPC patients.

IMPORTANCE: Inflammatory status is associated with outcome in oral squamous cell carcinoma (OSCC). Combining the preoperative neutrophil to lymphocyte ratio (NLR) and histopathologic features may provide clinicians with more exact information regarding the prognosis of OSCC. OBJECTIVE: To compare the prognostic performance of the routinely used pathologic TNM staging with a new staging category that incorporates the NLR and histopathologic features. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 396 patients with newly diagnosed OSCC who underwent major surgery at a medical center from January 1, 2006, through December 31, 2013. Follow-up was completed on October 31, 2015, and data analysis was performed from January 1, 2016, through April 30, 2016. MAIN OUTCOMES AND MEASURES: The multivariate Cox proportional hazards regression model was used to determine the clinical or pathologic factors associated with 5-year disease-specific survival (DSS), and these factors were assigned integer points to create a new staging category. The monotonicity and discriminatory ability of the pathologic TNM staging and new staging category were evaluated with the linear trend χ2 test, Akaike information criterion, and Harrell C statistic. RESULTS: In total, 396 patients who underwent major surgery with curative intent for OSCC with or without adjuvant therapy were included in this study (mean [SD] age, 53 [11] years; 367 men [92.7%] and 29 women [7.3%]). Perineural invasion (adjusted hazard ratio [aHR], 1.74; 95% CI, 1.23-2.46), high NLR (aHR, 1.60; 95% CI, 1.11-2.30), advanced pT (T3 + T4) classification (aHR, 1.59; 95% CI, 1.13-2.25), and advanced pN (N2) classification (aHR, 3.96; 95% CI, 2.78-5.63) were independent prognostic survival factors. The β coefficients from the Cox proportional hazards regression model were used to develop an integer-based weighted point system (perineural invasion, score of 1; NLR, score of 1; advanced pT, score of 1; and advanced pN, score of 3). The summations of these risk scores were stratified for the new staging category as follows: new stage I, score of 0; new stage II, score of 1; new stage III, score of 2 or 3; and new stage IV, score of 4 to 6. Compared with the American Joint Committee on Cancer staging category, this new staging category provided better monotonicity with a higher linear trend χ2 value (106 vs 49), better discriminatory ability with smaller Akaike information criterion (1497 vs 1533), and greater Harrell C statistic (0.73 vs 0.69) for 5-year DSS. The results remained robust after adjusting other risk factors. CONCLUSIONS AND RELEVANCE: In this study, new staging category had better DSS discriminatory ability and could help to identify high-risk patients for intense adjuvant therapy.

Objectives:Recently, molecular medicine targeting Folate Receptor Alpha (FOLR1), which mediates intracellular folate uptake and tumor cell proliferation, has been identified in several malignancies. However, the association between FOLR1 expression and rectal cancer remains unclear. Methods:Immunostaining of FOLR1 was performed on biopsy specimens from 172 rectal cancer patients undergoing preoperative chemoradiotherapy (CRT). FOLR1 expression was measured and divided into low (0+-2+) or high (3+-4+) level. Correlations between FOLR1 status and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival, and metastasis-free survival (MeFS) were analyzed, retrospectively. Results:High FOLR1 expression was significantly associated with advanced post-treatment tumor and nodal status (T3-4; N1-2, P= .001), vascular invasion (P= .042), perineural invasion (P= .012), and poor regression change after CRT (P= .001). In uni- and multi-variable survival analysis, FOLR1 overexpression remained a significant predictor of lower DSS (hazard ratio [HR], 2.328; 95% confidence interval [CI], 1.014-5.344; P= .046) and MeFS (HR, 2.177; 95% CI, 1.000-1.1286; P= .050). Conclusion: These results indicate that high FOLR1 status is associated with aggressive tumor behavior, poor response to CRT, and worse survival. Therefore, FOLR1 expression at initial biopsy may be useful in predicting outcomes and also be a target for the exploration of FOLR1-based therapeutic agents.

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