Our study showed safety and efficacy of PD-1 blockade in advanced melanoma patients in China with predominantly acral and mucosal subtypes. This is the largest prospective research focusing on differential clinical responses and unique mutation signatures among melanoma subtypes in China based on the whole-exome sequencing and RNA-sequencing profiling. we found CDK4 or CCND1(Cyclin D1) amplifications occurred more often in acral and mucosal melanoma than in non-acral cutaneous melanoma. CCND1 copy number variation as a part of 11q13 genomic amplification, occurred exclusively in acral and mucosal subtypes and correlated with poor response to PD-1 blockade treatment, suggesting a potential CDK4/6 targeting therapy or combination strategy of CDK4/6 inhibitor with anti-PD-1 for CCND1 amplified melanomas. Our results showed that for acral and mucosal subtypes in particular, combination treatment strategies are likely needed to further improve the clinical outcome of PD-1 blockade.Research.
The purpose of this study was to clarify the outcome of the ratio between metastatic and examined lymph nodes (N ratio) in gastric cancer patients with < or =15 examined lymph nodes after D2 lymphadenectomy. A retrospective study was performed in 906 patients with gastric cancer who had undergone D2 resection. Patients with < or =15 examined lymph nodes (group 1, n = 729) and those with >15 lymph nodes (group 2, n = 177) were analyzed separately. N ratio categories were identified as follows: N ratio 0, 0%; N ratio 1, 1% to 9%; N ratio 2, 10% to 25%; N ratio 3, >25%. Univariate analysis found that both the tumor, node, metastasis system (N staging system) and N ratio system well classified patients with significantly different prognosis. By multivariate analysis, only the N ratio classification was retained as an independent prognostic factor in both group 1 and 2 compared with the N stage system. Furthermore, when patients were divided into four groups according to the number of lymph nodes examined (1 to 3, 4 to 7, 8 to 11, and 12 to 15), the 5-year survival rates remained similar between groups according to the same N ratio (p > .05). Positive N ratio classification is a better prognostic tool compared with N staging system after D2 resection in patients with gastric cancer. It can prevent stage migration and can be used regardless of the examined number of lymph nodes.
BackgroundThe prognostic value of preoperative controlling nutritional status (CONUT) has been reported in many malignancies. In present study, we aimed to clarify the prognostic impact of CONUT in gastric cancer (GC) receiving curative resection and adjuvant chemotherapy.MethodsWe retrospectively reviewed 697 consecutive patients undergoing curative surgery followed by adjuvant chemotherapy for Stage II-III GC between November 2000 and September 2012. Patients were classified into high (≥3) and low (≤2) CONUT groups according to the receiver operating characteristic (ROC) analysis.ResultsOf the included patients, 217 (31.1%) belonged to the high CONUT group. The high CONUT group had a significantly lower 5-year cancer-specific survival (CSS) rate than the low CONUT group (39.3 vs. 55.5%, P < 0.001). High CONUT score was significantly associated with larger tumor size, more lymph node metastasis, and poorer nutritional status, including lower body mass index (BMI), higher prognostic nutritional index (PNI) and the presence of preoperative anemia (all P < 0.05). Multivariate analysis revealed that CONUT score was an independent prognostic factor (HR: 1.553; 95% CI: 1.080–2.232; P = 0.017). Of note, in the low PNI group, CONUT score still effectively stratified CSS (P = 0.016). Furthermore, the prognostic significance of CONUT score was also maintained when stratified by TNM stage (all P < 0.05).ConclusionsCONUT score is considered a useful nutritional marker for predicting prognosis in stage II-III GC patients undergoing curative resection and adjuvant chemotherapy, and may help to facilitate the planning of preoperative nutritional interventions.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4616-y) contains supplementary material, which is available to authorized users.
Expression of calreticulin is associated with infiltration of T-cells, which implies that a low expression level of molecular marker may represent a new mechanism underlying immune escape in colon cancer.
BackgroundThe prognostic significance of Epstein-Barr virus (EBV) infection in gastric cancer (GC) remains unclear. Recently, a number of studies have investigated the association between EBV infection and the prognosis of GC with controversial results. We therefore conducted a meta-analysis to assess its prognostic significance.MethodsPubMed and EMBASE were searched for studies up to October 1, 2014. We investigated the association between EBV infection with survival in patients with GC. The pooled hazard ratio (HR) and its 95 % confidence interval (CI) were calculated to evaluate risk.ResultsA final analysis of 8,336 patients with GC from 24 studies was performed. Our analysis results indicated that the pooled HR was 0.67 (95 % CI: 0.55–0.79; Z = 11.18, P < 0.001). Subgroup analyses stratified by region revealed that the protective role of EBV infection only remained in the Asian population (HR: 0.62, 95 % CI: 0.48–0.75; P < 0.001). When stratified by study quality and statistical methodology, the protective role could also be identified in high quality studies (HR: 0.67, 95 % CI: 0.55–0.79) and in univariate analysis studies (HR: 0.62, 95 % CI: 0.50–0.74). There was no evidence of significant heterogeneity and publication bias.ConclusionsThe presence of EBV has a favorable impact on GC patient’s survival, especially in an Asian population. Future updated studies, especially large-scale randomized controlled studies stratified by region, are warranted as validation studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1813-9) contains supplementary material, which is available to authorized users.
AimTo evaluate the prognostic efficacy of the 7th edition tumor–node–metastasis (TNM) classification compared with the 6th edition in gastric cancer patients.MethodsA total of 1,503 gastric cancer patients undergoing surgical resection were staged using the 6th and 7th edition staging systems. Homogeneity, discriminatory ability, and monotonicity of gradients of the two systems were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations.ResultsSignificant differences in 5-year survival rates were observed for the T, N, and M subgroups using the 7th edition system, except for stage N2 and N3 patients in the 6th edition system. There were no significant differences in survival between IB and IIA in the 7th edition system. Patients with stage IV disease due to T4/N3 in the 6th edition system who were downstaged to stage III in the 7th edition system had significantly better survival than those who remained at stage IV. The 7th edition system had higher linear trend and likelihood ratio χ2 scores, and smaller AIC values compared with those for the 6th edition, which represented the optimum prognostic stratification.ConclusionsOur study suggests that the 7th edition system performs better than the 6th edition in several aspects.
BackgroundThis study compared the performance of endoscopic ultrasonography (EUS) and multislice spiral computed tomography (MSCT) in the preoperative staging of gastric cancer.Methodology/Principal FindingsA total of 610 patients participated in this study, all of whom had undergone surgical resection, had confirmed gastric cancer and were evaluated with EUS and MSCT. Tumor staging was evaluated using the Tumor-Node-Metastasis (TNM) staging and Japanese classification. The results from the imaging modalities were compared with the postoperative histopathological outcomes. The overall accuracies of EUS and MSCT for the T staging category were 76.7% and 78.2% (P=0.537), respectively. Stratified analysis revealed that the accuracy of EUS for T1 and T2 staging was significantly higher than that of MSCT (P<0.001 for both) and that the accuracy of MSCT in T3 and T4 staging was significantly higher than that of EUS (P<0.001 and 0.037, respectively). The overall accuracy of MSCT was 67.2% when using the 13th edition Japanese classification, and this percentage was significantly higher than the accuracy of EUS (49.3%) and MSCT (44.6%) when using the 6th edition UICC classification (P<0.001 for both values).Conclusions/SignificanceOur results demonstrated that the overall accuracies of EUS and MSCT for preoperative staging were not significantly different. We suggest that a combination of EUS and MSCT is required for preoperative evaluation of TNM staging.
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