对膀胱进行放射治疗具有挑战性，因为它是一个可移动、可变形的结构。剂量递增的适应性图像引导放疗可以改善治疗结果。 RAIDER 旨在证明这种时间表的安全性。RAIDER 是一项国际 2 期非比较随机对照试验 (ISRCTN26779187)。单灶 T2-T4a 尿路上皮膀胱癌患者被随机 (1:1:2) 接受标准全膀胱放疗 (WBRT)、标准剂量适应性放疗 (SART) 或剂量递增适应性放疗 (DART)。独立招募两个分馏（f）时间表。 WBRT 和 SART 剂量为 55 Gy/20f 或 64 Gy/32f，DART 剂量为 60 Gy/20f 或 70 Gy/32f。对于 SART 和 DART，每天选择放射治疗计划（小、中或大）。主要终点是出现与放疗相关的晚期不良事件通用术语标准≥3级毒性的患者比例；该试验旨在排除 DART 的 >20% 毒性。2015 年 10 月至 2020 年 4 月期间，共有 345 名患者被随机分组​​：20f/32f 队列中 41/46 WBRT、41/46 SART 和 81/90 DART 患者， 分别。中位年龄为 72/73 岁； 78%/85% 患有 T2 肿瘤，46%/52% 接受新辅助化疗，70%/71% 接受放射增敏治疗。中位随访时间为 42.1/38.2 个月。计划进行 DART 的 77 名 20f 参与者中的 66 名 (86%) 和 82 名 32f 参与者中的 74 名 (90%) 满足强制性中期计划剂量限制。 58 名接受 20f DART 的患者中，有 1 名患者报告了与放疗相关的 3 级以上毒性（90% 置信区间 [CI] 0.1, 7.9），而 56 名接受 32f DART 的患者中，0 名报告了与放疗相关的 3 级毒性。 WBRT SART 的两年总生存率为 77% (95% CI 69, 82)，DART 为 80% (95% CI 73, 85)（风险比 = 0.84，95% CI 0.59, 1.21，p = 0.4）。 345 名参与者中有 13 名 (3.8%) 接受了挽救性膀胱切除术。≥3 级晚期毒性较低。 DART 的实施安全可行，符合预设的毒性阈值。疾病相关的结果对于剂量递增的治疗来说是有希望的，其挽救性膀胱切除率较低，总体生存率与膀胱切除队列相似。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule.RAIDER is an international phase 2 noncomparative randomised controlled trial (ISRCTN26779187). Patients with unifocal T2-T4a urothelial bladder cancer were randomised (1:1:2) to standard whole bladder radiotherapy (WBRT), standard-dose adaptive radiotherapy (SART), or dose-escalated adaptive radiotherapy (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 55 Gy/20f or 64 Gy/32f, and DART dose was 60 Gy/20f or 70 Gy/32f. For SART and DART, a radiotherapy plan (small, medium, or large) was chosen daily. The primary endpoint was the proportion of patients with radiotherapy-related late Common Terminology Criteria for Adverse Events grade ≥3 toxicity; the trial was designed to rule out >20% toxicity with DART.A total of 345 patients were randomised between October 2015 and April 2020: 41/46 WBRT, 41/46 SART, and 81/90 DART patients in the 20f/32f cohorts, respectively. The median age was 72/73 yr; 78%/85% had T2 tumours, 46%/52% had neoadjuvant chemotherapy, and 70%/71% had radiosensitising therapy. The median follow-up was 42.1/38.2 mo. Sixty-six of 77 (86%) 20f and 74 of 82 (90%) 32f participants planned for DART met the mandatory medium plan dose constraints. Radiotherapy-related grade ≥3 toxicity was reported in one of 58 patients (90% confidence interval [CI] 0.1, 7.9) with 20f DART and zero of 56 patients with 32f DART. Two-year overall survival was 77% (95% CI 69, 82) for WBRT + SART and 80% (95% CI 73, 85) for DART (hazard ratio = 0.84, 95% CI 0.59, 1.21, p = 0.4). Thirteen of 345 (3.8%) participants had salvage cystectomy.Grade ≥3 late toxicity was low. DART was safe and feasible to deliver, meeting preset toxicity thresholds. Disease-related outcomes are promising for dose-escalated treatments, with a low salvage cystectomy rate and overall survival similar to that seen in cystectomy cohorts.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.