Icon Cancer Centre, Richmond, Australia.
Urology Department, Eastern Health, Box Hill Hospital, Box Hill, Australia.
Radiat Oncol. 2022 Jul 25;17(1):131. doi: 10.1186/s13014-022-02103-5.
Dose-escalation to above 80 Gy during external beam radiotherapy for localised prostate cancer leads to improved oncological outcomes but also substantially increased rectal toxicity. The aim of this study was to demonstrate the safety and efficacy of escalating the dose to 82 Gy following insertion of a peri-rectal hydrogel spacer (HS) prior to radiotherapy.
This was a single arm, open-label, prospective study of men with localised prostate cancer who were prescribed a course of intensity modulated radiotherapy escalated to 82 Gy in 2 Gy fractions following insertion of the SpaceOAR™ HS (Boston Scientific, Marlborough, MA). Patients were prescribed a standard course of 78 Gy in 2 Gy fractions where rectal dose constraints could not be met for the 82 Gy plan. The co-primary endpoints were the rate of grade 3 gastrointestinal (GI) and genitourinary (GU) adverse events (CTCAE, v4), and patient-reported quality of life (QoL) (EORTC QLQ-C30 and PR25 modules), up to 37.5 months post-treatment.
Seventy patients received treatment on the study, with 64 (91.4%) receiving an 82 Gy treatment course. The median follow-up time post-treatment was 37.4 months. The rate of radiotherapy-related grade 3 GI and GU adverse events was 0% and 2.9%, respectively. There were 2 (2.9%) grade 3 adverse events related to insertion of the HS. Only small and transient declines in QoL were observed; there was no clinically or statistically significant decline in QoL beyond 13.5 months and up to 37.5 months post-treatment, compared to baseline. No late RTOG-defined grade ≥ 2 GI toxicity was observed, with no GI toxicity observed in any patient at 37.5 months post-treatment. Nine (12.9%) patients met criteria for biochemical failure within the follow-up period.
Dose-escalation to 82 Gy, facilitated by use of a hydrogel spacer, is safe and feasible, with minimal toxicity up to 37.5 months post-treatment when compared to rates of rectal toxicity in previous dose-escalation trials up to 80 Gy. Trials with longer follow-up of oncological and functional outcomes are required to robustly demonstrate a sustained widening of the therapeutic window. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12621000056897 , 22/01/2021. Retrospectively registered.
在局部前列腺癌的外照射放射治疗中，剂量递增至 80Gy 以上可改善肿瘤学结果，但也会显著增加直肠毒性。本研究旨在证明在放射治疗前插入直肠周围水凝胶间隔物（HS）后将剂量递增至 82Gy 的安全性和有效性。
这是一项单臂、开放标签、前瞻性研究，纳入了局部前列腺癌患者，他们接受了调强放疗，在插入 SpaceOAR™ HS（波士顿科学公司，马萨诸塞州马尔伯勒）后剂量递增至 82Gy，分 2Gy 剂量。患者接受了标准的 78Gy 治疗方案，其中 82Gy 方案的直肠剂量限制无法满足。主要终点是治疗后 37.5 个月时发生 3 级胃肠道（GI）和泌尿生殖系统（GU）不良事件（CTCAE，v4）的发生率，以及患者报告的生活质量（EORTC QLQ-C30 和 PR25 模块）。
70 名患者接受了该研究的治疗，其中 64 名（91.4%）接受了 82Gy 的治疗方案。治疗后中位随访时间为 37.4 个月。与放射治疗相关的 3 级 GI 和 GU 不良事件的发生率分别为 0%和 2.9%。有 2 例（2.9%）与 HS 插入相关的 3 级不良事件。仅观察到 QoL 的微小和短暂下降；与基线相比，治疗后 13.5 个月及以上至 37.5 个月，QoL 无临床或统计学意义的下降。未观察到 RTOG 定义的任何 3 级及以上的 GI 毒性，治疗后 37.5 个月时，任何患者均未观察到任何 GI 毒性。9 名（12.9%）患者在随访期间符合生化失败标准。
通过使用水凝胶间隔物将剂量递增至 82Gy 是安全可行的，与之前 80Gy 剂量递增试验中直至 37.5 个月的直肠毒性相比，其毒性最小。需要进行更长时间的随访，以更有力地证明肿瘤学和功能结局的治疗窗口持续扩大。
