Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II-III gastric cancer

Background Circulating tumor DNA(ctDNA)is a promising biomarker for predicting relapse in multiple solid cancers.However,the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer(GC).Here,we aimed to evaluate the predictive value of ctDNA in this context.Methods From 2016 to 2019,100 patients with stage II/III resectable GC were recruited in this prospective cohort study(NCT02887612).Primary tumors were collected during surgical resection,and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy(ACT).Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes.The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2%of the primary tumors.Results Compared with ctDNA-negative patients,patients with positive postoperative ctDNA had moderately higher risk of recurrence[hazard ratio(HR)=2.74,95%confidence interval(CI)=1.37–5.48;P=0.003],while patients with positive post-ACT ctDNA showed remarkably higher risk(HR=14.99,95%CI=3.08-72.96;P<0.001).Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival(RFS).Moreover,post-ACT ctDNA achieved better predictive performance(sensitivity,77.8%;specificity,90.6%)than both postoperative ctDNA and serial cancer antigen.A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index(0.78;95%CI=0.71–0.84)than the model without ctDNA(0.71;95%CI=0.64–0.79;P=0.009).Conclusions Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC,and the combination of tissue-based and circulating tumor features could achieve better risk prediction.

Additional gastrectomy in early-stage gastric cancer after non-curative endoscopic resection:a meta-analysis

Background and objective:The role of additional gastrectomy after non-curative endoscopic resection remains uncertain.The present meta-analysis aimed to explore the risk factors for early-stage gastric-cancer patients after non-curative endoscopic resection and evaluate the efficacy of additional gastrectomy.Methods:Relevant studies that reported additional gastrectomy after non-curative endoscopic resection were comprehensively searched in MedLine,Web of Science and EMBASE.We first investigated the risk factors for residual tumor and lymph-node metastasis after non-curative endoscopic resection and then analysed the survival outcome,including 5-year overall survival(OS)and 5-year disease-free survival,of additional gastrectomy.Results:Twenty-one studies comprising 4870 cases were included in the present study.We found that residual tumor was associated with larger tumor size(>3 cm)(odds ratio[OR]=2.81,P<0.001),undifferentiated tumor type(OR=1.78,P=0.011)and positive horizontal margin(OR=9.78,P<0.001).Lymph-node metastasis was associated with larger tumor size(>3 cm)(OR=1.73,P<0.001),elevated tumor type(OR=1.60,P=0.035),deeper tumor invasion(>SM1)(OR=2.68,P<0.001),lymphatic invasion(OR=4.65,P<0.001)and positive vertical margin(OR=2.30,P<0.001).Patients who underwent additional gastrectomy had longer 5-year OS(hazard ratio[HR]=0.34,P<0.001),5-year disease-free survival(HR=0.52,P=0.001)and 5-year disease-specific survival(HR=0.50,P<0.001)than those who did not.Moreover,elderly patients also benefited from additional gastrectomy regarding 5-year OS(HR=0.41,P=0.001).Conclusions:Additional gastrectomy with lymph-node dissectionmight improve the survival of early-stage gastric-cancer patients after non-curative endoscopic resection.However,risk stratification should be performed to avoid excessive treatment.

JMJD3 promotes esophageal squamous cell carcinoma pathogenesis through epigenetic regulation of MYC

Dear Editor,Esophageal squamous cell carcinoma(ESCC)is a common cancer worldwide with a 5-year survival rate less than 25%.Reliable molecular markers that could serve as predictors for diagnosis and treatment for ESCC patients are greatly needed.The dysregulation of epigenetic control is one of the common features in cancer.JMJD3 is a histone demethylase specific for H3K27me3/me2 that switches a gene from its repressive state to an active form.1 The dysregulation of JMJD3 is reported to play key roles in many cancer progressions.Recently,JMJD3 was reported to be overexpressed in ESCC,2 but the potential mechanism of JMJD3 in ESCC remains poorly understood.