Postoperative chemoradiotherapy with capecitabine and oxaliplatin vs.capecitabine for pathological stage N2 rectal cancer

Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.

Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients:A prospective phaseⅡstudy

Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal cancer.However,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this therapy.Therefore,there is a need for a more suitable radiotherapy combination regimen for this population.This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)score.Methods:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled.They were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive radiotherapy.The primary endpoint was the locoregional control(LRC)rate.Results:A total of 55 patients who met the study criteria were enrolled.After completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 patients.The median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]months.The LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire population.The overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,respectively.Surgery was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events occurred.Conclusions:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypl stage after neoadjuvant chemo-radiotherapy versus de novo stage pl cohort:A propensity score-matched analysis

Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 cohort that received definitive surgery for early disease.Method：From January 2008 to December 2013,449 consecutive patients with rectal cancer were treated and their outcome maintained in a database.Patients with LARC underwent total mesorectal excision（TME）surgery at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I group pertains to patients whose initially limited disease was not upstaged after TME surgery alone.After propensity score matching（PSM）,comparisons of local regional control（LC）,distant metastasis-free survival（DMFS）,disease-free survival（DFS）and overall survival（OS）were performed using Kaplan-Meier analysis and log-rank test between yp I and p I groups.Down-staging depth score（DDS）,a novel method of evaluating CRT response,was used for subset analysis.Results：Of the 449 patients,168 matched cases were generated for analysis.Five-year LC,DMFS,DFS and OS for stage p I vs.yp I groups were 96.7%vs.96.4%（P=0.796）,92.7%vs.73.6%（P=0.025）,91.2%vs.73.6%（P=0.080）and 93.1%vs.72.3%（P=0.040）,respectively.In the DDS-favorable subset of the yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,respectively）.Conclusions：LC was comparable in both groups;however,distant metastasis developed more frequently in down-staged LARC than de novo early stage cases,reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response.DDS can be an indicator to identify a subset of the yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.

Down-staging depth score could be a survival predictor for locally advanced gastric cancer patients after preoperative chemoradiotherapy

Objective:The predictive effect of preoperative chemoradiotherapy(CRT)is low and difficult in guiding individualized treatment.We examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative CRT.Methods:From April 2012 to April 2019,95 patients with locally advanced gastric cancer who received preoperative concurrent CRT and who were enrolled in three prospective studies were included.All patients were stage T_(3/4) N_(+).Local control,distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)were evaluated.Clinicopathological factors related to long-term prognosis were analyzed using univariate and multivariate analyses.The down-staging depth score(DDS),which is a novel method of evaluating CRT response,was used to predict long-term outcomes.Results:The median follow-up period for survivors was 30 months.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve predicted by the DDS was 0.728,which was better than the pathological complete response(pCR),histological response and ypN0.Decision curve analysis further affirmed that DDS had the largest net benefit.The DDS cut-off value was 4.pCR and ypN0 were associated with OS(P=0.026 and 0.049).Surgery and DDS are correlated with DMFS,DFS and OS(surgery:P=0.001,<0.001 and<0.001,respectively;and DDS:P=0.009,0.013 and 0.032,respectively).Multivariate analysis showed that DDS was an independent prognostic factor of DFS(P=0.021).Conclusions:DDS is a simple,short-term indicator that was a better surrogate endpoint than pCR,histological response and ypN0 for DFS.

Nomogram for predicting the overall survival of patients after D2/R0 resection and chemoradiotherapy for stage Ⅲ gastric cancer or gastroesophageal junction cancer

Objective:To explore the independent factors associated with the overall survival(OS)after D2/R0 resection and adjuvant chemoradiotherapy(CRT)for stage Ⅲ gastric cancer(GC)and gastroesophageal junction(GEJ)cancer,and establish and validate a nomogram model to predict the OS in this patient population.Methods:A total of 569 stage Ⅲ GC or GEJ cancer patients who underwent D2/R0 resection and adjuvant CRT at our center from January 2013 to May 2018 were retrospectively enrolled in this study.The patients were randomly divided into training and validation cohorts in a 3:1 ratio.In the training cohort,univariate and multivariate analysis were conducted to identify clinical factors associated with OS,and a nomogram model was established on the basis of the independent factors.The concordance index(C-index)and the calibration curve were used to validate the prediction power of the nomogram.Results:Overall,427 and 142 patients were enrolled in the training and validation cohorts,respectively.In the univariate and multivariate analyses,age,Lauren's classification,TNM stage,and administration of adjuvant CRT were independent factors for OS to construct the nomogram.The C-index values were 0.654 and 0.613 in the training and validation cohorts,respectively.The calibration curves were identical to the actual OS.Risk stratification based on the nomogram model showed good risk stratification for OS in both groups.Conclusion:Our study included adjuvant CRT as a predictive factor and established a nomogram model for predicting the OS in patients with stage III GC or GEJ after D2/R0 resection and adjuvant therapy.This nomogram could facilitate more individualized prediction of OS in clinical practice.