BACKGROUND Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. Adjuvant chemotherapy is advised in several international guidelines, although the survival benefit remains unclear and compliance is poor. The current multidisciplinary approach has led to major improvements in local control, yet the occurrence of distant metastases has not decreased accordingly. The combination of short-course radiotherapy (SCRT) and chemotherapy in the waiting period before surgery might have several benefits, including higher compliance, downstaging and better effect of systemic therapy. METHODS This is an investigator-initiated, international multicentre randomized phase III trial. High-risk rectal cancer patients were randomized to SCRT followed by chemotherapy (6 cycles CAPOX or alternatively 9 cycles FOLFOX4) and subsequent surgery, or long-course radiotherapy (25-28 × 2-1.8 Gy) with concomitant capecitabine followed by surgery and optional postoperative chemotherapy (8 cycles CAPOX or 12 cycles FOLFOX4) according to local institutions' policy. The primary endpoint is time to disease-related treatment failure. Here, we report the compliance, toxicity and postoperative complications in both study groups. FINDINGS Between June 2011 and June 2016, 920 patients were enrolled. Of these, 901 were evaluable (460 in the experimental arm and 441 in the standard arm). All patients in the experimental arm received 5 × 5 Gy radiotherapy, and 84% of all patients received at least 75% of the prescribed chemotherapy. In the standard arm, the compliance for CRT was 94% and 57% for postoperative chemotherapy. Toxicity ≥grade 3 occurred in 48% of patients in the experimental arm, compared to 25% of patients in the standard arm during preoperative treatment and 35% of patients during postoperative chemotherapy. No statistically significant differences in surgical procedures or postoperative complications were observed. INTERPRETATION High compliance (84%) of preoperative systemic treatment could be achieved with the experimental approach. Although considerable toxicity was observed during preoperative therapy, this did not lead to differences in surgical procedures or postoperative complications. Longer follow-up time is needed to assess the primary endpoint and related outcomes.

中文翻译：

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短程放疗继以术前化疗和手术治疗高危直肠癌的依从性和耐受性——国际随机 RAPIDO 试验的结果

背景 术前放化疗 (CRT) 和全直肠系膜切除术被广泛接受为高危直肠癌的护理标准。多项国际指南均建议进行辅助化疗，但生存获益尚不清楚且依从性较差。目前的多学科方法已导致局部控制的重大改进，但远处转移的发生率并未相应减少。术前等待期短程放疗（SCRT）和化疗相结合可能有几个好处，包括更高的依从性、降期和更好的全身治疗效果。方法 这是一项由研究者发起的国际多中心随机 III 期试验。高危直肠癌患者随机接受 SCRT 继以化疗（6 个周期 CAPOX 或 9 个周期 FOLFOX4）和后续手术，或长期放疗（25-28 × 2-1.8 Gy）联合卡培他滨继以手术和可选根据当地机构的政策，术后化疗（8 个周期 CAPOX 或 12 个周期 FOLFOX4）。主要终点是疾病相关治疗失败的时间。在这里，我们报告了两个研究组的依从性、毒性和术后并发症。结果 2011 年 6 月至 2016 年 6 月期间，共招募了 920 名患者。其中，901 个是可评估的（实验组 460 个，标准组 441 个）。实验组的所有患者均接受 5 × 5 Gy 放疗，84% 的患者接受了至少 75% 的处方化疗。在标准组中，CRT 的依从性为 94%，术后化疗的依从性为 57%。实验组 48% 的患者出现≥ 3 级的毒性，而标准组术前治疗期间为 25%，术后化疗期间为 35%。没有观察到外科手术或术后并发症的统计学显着差异。解释 使用实验方法可以实现术前全身治疗的高依从性 (84%)。尽管在术前治疗期间观察到相当大的毒性，但这并没有导致手术程序或术后并发症的差异。需要更长的随访时间来评估主要终点和相关结果。实验组 48% 的患者出现≥ 3 级的毒性，而标准组术前治疗期间为 25%，术后化疗期间为 35%。没有观察到外科手术或术后并发症的统计学显着差异。解释 使用实验方法可以实现术前全身治疗的高依从性 (84%)。尽管在术前治疗期间观察到相当大的毒性，但这并没有导致手术程序或术后并发症的差异。需要更长的随访时间来评估主要终点和相关结果。实验组 48% 的患者出现≥ 3 级的毒性，而标准组术前治疗期间为 25%，术后化疗期间为 35%。没有观察到外科手术或术后并发症的统计学显着差异。解释 使用实验方法可以实现术前全身治疗的高依从性 (84%)。尽管在术前治疗期间观察到相当大的毒性，但这并没有导致手术程序或术后并发症的差异。需要更长的随访时间来评估主要终点和相关结果。相比之下，标准组在术前治疗期间为 25% 的患者和在术后化疗期间为 35% 的患者。没有观察到外科手术或术后并发症的统计学显着差异。解释 使用实验方法可以实现术前全身治疗的高依从性 (84%)。尽管在术前治疗期间观察到相当大的毒性，但这并没有导致手术程序或术后并发症的差异。需要更长的随访时间来评估主要终点和相关结果。相比之下，标准组在术前治疗期间为 25% 的患者和在术后化疗期间为 35% 的患者。没有观察到外科手术或术后并发症的统计学显着差异。解释 使用实验方法可以实现术前全身治疗的高依从性 (84%)。尽管在术前治疗期间观察到相当大的毒性，但这并没有导致手术程序或术后并发症的差异。需要更长的随访时间来评估主要终点和相关结果。尽管在术前治疗期间观察到相当大的毒性，但这并没有导致手术程序或术后并发症的差异。需要更长的随访时间来评估主要终点和相关结果。尽管在术前治疗期间观察到相当大的毒性，但这并没有导致手术程序或术后并发症的差异。需要更长的随访时间来评估主要终点和相关结果。