Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Radiotherapy Department, The Royal Marsden NHS Foundation Trust, London, UK.
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Radiotherapy Department, The Royal Marsden NHS Foundation Trust, London, UK.
Clin Oncol (R Coll Radiol). 2023 Sep;35(9):586-597. doi: 10.1016/j.clon.2023.05.002. Epub 2023 May 9.
Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination.
Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests.
Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts.
Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.
在放射治疗中加入同期（化疗）可改善肌层浸润性膀胱癌患者的预后。最近的一项荟萃分析显示，与 64 Gy/32 次相比，55 Gy/20 次的分割方案在局部区域疾病控制方面具有更好的侵袭性。在 RAIDER 临床试验中，接受 20 或 32 次根治性放疗的患者按 1:1:2 随机分为标准放疗或标准剂量或递增剂量适应性放疗。允许新辅助化疗和同期治疗。我们报告了按同期治疗-分割方案组合进行的急性毒性的探索性分析。
参与者为单灶膀胱尿路上皮癌，分期为 T2-T4a N0 M0。在放射治疗期间每周和治疗开始后 10 周评估急性毒性（不良事件通用术语标准）。在每个分割队列内，使用 Fisher 精确检验对任何急性期间报告治疗出现 2 级或更高级别的泌尿生殖、胃肠道或其他不良事件的患者比例进行非随机比较。
2015 年 9 月至 2020 年 4 月，从 46 个中心招募了 345 名（20 个剂量组 163 名，32 个剂量组 182 名）患者。中位年龄为 73 岁；49%接受新辅助化疗；71%接受同期治疗，最常用的是氟尿嘧啶/丝裂霉素 C：20 个剂量组 44/114（39%）；32 个剂量组 94/130（72%）。在 20 个剂量组中，与单独放疗相比，接受同期治疗的患者胃肠道 2 级+毒性发生率更高[54/111（49%）与 7/49（14%），P<0.001]，但在 32 个剂量组中无差异（P=0.355）。吉西他滨的胃肠道 2 级+毒性最高，在 32 个剂量组中不同治疗方法之间存在显著差异（P=0.006），而在 20 个剂量组中则无显著差异（P=0.099）。在 20 个或 32 个剂量组中，同期治疗的泌尿生殖系统 2 级+毒性之间无差异。
2 级+急性不良事件很常见。毒性谱因同期治疗类型而异；接受吉西他滨治疗的患者胃肠道毒性发生率似乎更高。
