作者
Jing Jin,Yuan Tang,Chen Hu,Li-Ming Jiang,Jun Jiang,Ning Li,Wen-Yang Liu,Si-Lin Chen,Shuai Li,Ning-Ning Lu,Yong Cai,Yong-Heng Li,Yuan Zhu,Guanghui Cheng,Hong-Yan Zhang,Xin Wang,Su-Yu Zhu,Jun Wang,Gao-Feng Li,Jia-Lin Yang,Kuan Zhang,Yihebali Chi,Lin Yang,Hai-Tao Zhou,Ai-Ping Zhou,Shuangmei Zou,Hui Fang,Shulian Wang,Haizeng Zhang,Xi-Shan Wang,Li-Chun Wei,Wen-Ling Wang,Shi-Xin Liu,Yuanhong Gao,Yexiong Li
摘要
PURPOSE To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node–positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m 2 , once a day] on day 1 and capecitabine [1,000 mg/m 2 , twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group ( P < .001). CONCLUSION Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.