We thank Sütcüoğlu et al,¹ Negri and Aschele,² and Yüksel³ for their comments on the STELLAR trial.⁴ The toxicity profile and effectiveness of hypofrationated radiotherapy (5 Gy × 5) and neoadjuvant chemotherapy for locally advanced rectal cancer (LARC) have been evaluated in three large randomized controlled trials (RCTs), including STELLAR, RAPIDO, and Polish II studies.^4-6 Despite the differences in clinical characteristics between trials, all three RCTs showed comparable outcomes between short-course hypofrationated radiotherapy combined with neoadjuvant chemotherapy and long-course concurrent chemoradiotherapy (CRT) followed by adjuvant chemotherapy in LARC in terms of survival and local control. The question is to what extent is any further evidence still required? In the STELLAR study,⁴ the 3-year cumulative incidence of locoregional recurrence of 8.4%-11.0% and 3-year DFS of 62.3%-64.5% were reasonable because of the inclusion of more patients with adverse clinical factors, such as middle low location only, more positive EMVI (47.9%), and MRF (56.3%). The STELLAR and Polish II trials only included patients with middle low rectal cancer,^4,6 whereas the RAPIDO and PRODIGE trials included patients with all sites of rectal cancer, with upper rectal cancer of 33% and 13%.^5,7 Moreover, approximately half patients (49.2%) in the STELLAR study had disease localized in low rectal cancer, which were slightly lower than 55.5% in the Polish II trial, but significantly higher than 23.9% in the RAPIDO trial and 36.9% in the PRODIGE trial, leading to a large proportion of our patients (43.2%) treated with abdominoperineal resection. The proportion of patients receiving abdominoperineal resection varied between trials, mainly because of the heterogeneity of eligibility criteria and surgical procedure. The different outcomes between trials can be partially attributable to the heterogeneous clinical characteristics in RCTs comparing the short-course hypofrationated radiotherapy (5 Gy × 5) and neoadjuvant chemotherapy and standard long-course CRT for rectal cancer.^4-6 The locoregional control and DFS rates in the STELLAR trial were higher than that in Polish II,⁶ but lower than that in RAPIDO and PRODIGE trials.^5,7

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回复 O. Sütcüoğlu 等人、F. Negri 等人和 BC Yüksel

我们感谢 Sütcüoğlu 等人、¹ Negri 和 Aschele、²和 Yüksel ³对 STELLAR 试验的评论。⁴包括 STELLAR、RAPIDO 和 Polish II 研究在内的三项大型随机对照试验 (RCT) 评估了大剂量放疗 (5 Gy × 5) 和新辅助化疗对局部晚期直肠癌 (LARC) 的毒性特征和有效性。^4-6尽管试验之间的临床特征存在差异，但所有三项随机对照试验均显示，在 LARC 中，短程大剂量放疗联合新辅助化疗与长程同步放化疗 (CRT) 继以辅助化疗在生存和局部控制方面的结果相当。问题是在多大程度上还需要进一步的证据？在 STELLAR 研究中，⁴局部区域复发的 3 年累积发生率为 8.4%-11.0%，3 年 DFS 为 62.3%-64.5% 是合理的，因为纳入了更多具有不良临床因素的患者，例如中低度仅位置，更积极的 EMVI (47.9%) 和 MRF (56.3%)。STELLAR 和 Polish II 试验仅包括中低位直肠癌患者，^4,6而 RAPIDO 和 PRODIGE 试验包括所有直肠癌部位的患者，上位直肠癌分别为 33% 和 13%。^5,7此外，STELLAR 研究中约有一半患者 (49.2%) 的疾病局限于低位直肠癌，略低于 Polish II 试验中的 55.5%，但显着高于 RAPIDO 试验中的 23.9% 和 PRODIGE 中的 36.9%试验，导致我们的大部分患者 (43.2%) 接受了腹会阴切除术。接受腹会阴切除术的患者比例因试验而异，主要是因为合格标准和手术程序的异质性。试验之间的不同结果可部分归因于 RCT 中的异质性临床特征，这些临床特征比较了直肠癌的短程大剂量放疗 (5 Gy × 5) 和新辅助化疗以及标准长程 CRT。^4-6STELLAR 试验中的局部区域控制率和 DFS 率高于 Polish II，⁶但低于 RAPIDO 和 PRODIGE 试验。^5,7