巴西-TNT:一项新辅助放化疗联合FOLFIRINOX对比常规放化疗治疗Ⅱ/Ⅲ期直肠癌的随机2期试验OACSTPCD

Background Neoadjuvant radiation and oxaliplatin-based systemic therapy(total neoadjuvant therapy,TNT)have been shown to increase response and organ-preservation rates in localized rectal cancer.However,trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait(W&W)approach for complete respond-ers.This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases com-plete response rates and the number of patients managed by W&W.Methods This was a pragmatic randomized phaseⅡ trial conducted in 2 Cancer Centers in Brazil that included patients with T3 or N+rectal adenocarcinoma.After com-pleting a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1∶1 to 4 cycles of mFOLFIRI-NOX(Oxaliplatin 85,irinotecan 150,5-FU 2400)-TNT-arm-or to the control arm,that did not include further neoadjuvant treatment.All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks af-ter the end of radiation.Patients with a clinical complete response were followed using a W&W protocol.The primary endpoint was complete response:clinical complete response(cCR)or pathological response(pCR).Results Between April 2021 and June 2023,55 patients were randomized to TNT and 53 to the control arm.Tumors were 74％stage 3,median distance from the anal verge was 6 cm,63％had an at-risk circumferential margin,and 33％an involved sphinc-ter.The rates of cCR+pCR were(31％)for TNT versus(17％)for controls[odds ratio(OR)2.19,95％CI 0.8-6.22,P=0.091)and rates of W&W were 16％and 9％(P＞0.05).Median follow-up was 8.1 months and recurrence rates were 16％versus 21％for TNT and controls(P＞0.05).Conclusions TNT with consolidation FOLFIRINOX is feasible and has high response rates,consistent with the current literature for TNT.