NCT03253744 is a phase I trial with the primary objective to identify the maximally tolerated dose (MTD) of salvage stereotactic body radiotherapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response. This trial was initially designed to test three therapeutic dose levels (DLs): 40Gy (DL1), 42.5Gy (DL2), and 45Gy (DL3) in 5 fractions. Intensity modulation was utilized to deliver the prescription dose to the MRI and PSMA-based PET imaging-defined gross tumor volume while simultaneously delivering 30Gy to an elective volume defined by the prostate gland. This phase I trial followed a 3+3 design with a 3-patient expansion at the maximum tolerated dose (MTD). Toxicities were scored until trial completion at two years post-SBRT utilizing CTCAE v5.0 criteria. Escalation was halted if two dose limiting toxicities (DLTs) occurred, defined as any persistent (>4 days) grade (G) 3 toxicity occurring within the first 3 weeks after SBRT or any ≥G3 GU or G4 GI toxicity thereafter. Between 08/2018 and 01/2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3,20-43 months). No grade 3-5 AEs related to study treatment were observed, and, thus, no DLTs occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late G2 GU toxicity. Therefore, the MTD was considered 42.5Gy in 5 fractions (DL2). One- and two-year biochemical progression free survival (bPFS) were 100% and 86% representing a single patient in the trial cohort with biochemical failure (PSA nadir+2.0) at 20 months post-treatment. The MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was considered to be 42.5Gy in 5 fractions producing an 86% 2-year bPFS, with one post-study failure at 20 months. The most frequent clinically significant toxicity was late G2 GU toxicity.

中文翻译：

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近距离放射治疗后放射性复发性前列腺癌挽救性立体定向放射治疗的 I 期试验

NCT03253744 是一项 I 期试验，主要目的是确定近距离放射治疗后局部前列腺癌复发患者挽救性立体定向放射治疗 (SBRT) 的最大耐受剂量 (MTD)。其他目标包括生化控制和成像反应。该试验最初设计为测试三种治疗剂量水平 (DL)：40Gy (DL1)、42.5Gy (DL2) 和 45Gy (DL3)，分 5 次进行。利用强度调制将处方剂量输送到 MRI 和基于 PSMA 的 PET 成像定义的总肿瘤体积，同时将 30Gy 输送到由前列腺定义的选择性体积。该 I 期试验采用 3+3 设计，以最大耐受剂量 (MTD) 扩大 3 名患者。使用 CTCAE v5.0 标准对毒性进行评分，直至 SBRT 后两年试验完成。如果发生两次剂量限制性毒性 (DLT)，则停止升级，DLT 定义为 SBRT 后前 3 周内发生的任何持续（>4 天）3 级毒性或此后任何 ≥G3 GU 或 G4 GI 毒性。2018年8月至2023年1月期间，9名患者接受了挽救性SBRT，观察时间中位数为22个月（Q1-Q3，20-43个月）。没有观察到与研究治疗相关的 3-5 级 AE，因此在观察期间没有发生 DLT。在临床显着的晚期 G2 GU 毒性发生率高的情况下，由于对 DL1 和 DL2 进行了出色的生化控制，因此通过修正停止了升级。因此，MTD 被认为是 5 次分割 (DL2) 中的 42.5Gy。一年和两年生化无进展生存率 (bPFS) 分别为 100% 和 86%，代表治疗后 20 个月时出现生化失败（PSA 最低值+2.0）的试验队列中的单个患者。用于治疗近距离放射治疗后前列腺内放射性复发的挽救性 SBRT 的 MTD 被认为是 42.5Gy，分为 5 次，产生 86% 的 2 年 bPFS，其中 1 次研究后在 20 个月时失败。最常见的临床显着毒性是 G2 GU 晚期毒性。