影像引导的风险体积适应性前列腺切除后放疗1期临床试验
A Phase 1 Trial of Image Guided Risk Volume-Adapted Postprostatectomy Radiation Therapy
影响因子:6.50000
分区:医学1区 Top / 肿瘤学2区 核医学2区
发表日期:2025 Jul 15
作者:
Krishnan R Patel, Esther Mena, Lindsay S Rowe, Holly Ning, Jason Cheng, Kilian Salerno, Erica Schott, Debbie-Ann Nathan, Erich P Huang, Liza Lindenberg, Peter Choyke, Baris Turkbey, Deborah E Citrin
摘要
本研究为一期临床试验，主要目标是确定在生化复发性前列腺癌的风险体积适应性高分割术后放疗（PORT）中可耐受的最紧凑剂量方案（DS）。次要终点包括生化无进展生存率和生活质量（QOL）。患者接受三种等效剂量方案（DS1：20次，DS2：15次，DS3：10次），逐步增加对影像定义的局部复发（等效剂量73 Gy3，2 Gy分次）区域的剂量，减少对前列腺床剩余部分（等效剂量48 Gy3，2 Gy分次）的剂量。剂量递增遵循标准的3+3设计，在最大耐受高分割方案中扩展6名患者。剂量限制性毒性定义为PORT完成后21天内出现持续超过4天的G3毒性或G4肠胃道（GI）或泌尿生殖系统毒性。通过扩展问卷（Expanded Prostate Cancer Index Composite）对生活质量进行纵向评估，最长24个月。2018年1月至2023年12月，共治疗15例患者（3例DS1，3例DS2，9例DS3），中位随访48个月。未在任何剂量方案中观察到剂量限制性毒性，故在DS3中扩展研究。24个月时G3 GI和泌尿系统毒性的累计发生率分别为7%和9%，未见G4事件。急性G2+ GI毒性为最常见的短暂不适。生活质量在随访期间在排尿失禁、GI和性功能方面短暂下降，但至24个月恢复到基线水平。生化无进展生存率在24和60个月均为91%。最大耐受的高分割剂量方案为DS3（前列腺床36.4 Gy，影像定义复发47.1 Gy，10个每日剂次）。未观察到G3以上事件。生活质量的短暂下降未持续至24个月。
Abstract
This was a phase 1 trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk volume-adapted, hypofractionated, postoperative radiation therapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression-free survival and quality of life (QOL).Patients were treated with 1 of 3 isoeffective DSs (DS1: 20 fractions, DS2: 15 fractions, and DS3: 10 fractions) that escalated the dose to the imaging-defined local recurrence (73 Gy3 equivalent dose in 2Gy fractions) and de-escalated the dose to the remainder of the prostate bed (48 Gy3 equivalent dose in 2Gy fractions). Escalation followed a standard 3 + 3 design with a 6-patient expansion at the maximally tolerated hypofractionated DS. Dose-limiting toxicity was defined as Common Terminology Criteria for Adverse Events v.4.0 grade (G) 3 toxicity lasting >4 days within 21 days of PORT completion or G4 gastrointestinal (GI) or genitourinary toxicities thereafter. QOL was assessed longitudinally through 24 months with the Expanded Prostate Cancer Index Composite short form.Between January 2018 and December 2023, 15 patients were treated (3 with DS1, 3 with DS2, and 9 with DS3). The median follow-up was 48 months. No dose-limiting toxicities were observed on any DS, and thus, expansion occurred at DS3. The cumulative incidence of G3 GI and genitourinary toxicity was 7% and 9% at 24 months, respectively, with no G4 events observed. Transient, acute G2+ GI toxicity was the most common. QOL worsened transiently during study follow-up in urinary incontinence, GI, and sexual subdomains but was similar to baseline by 24 months. The biochemical progression-free survival was 91% at both 24 and 60 months.The maximally tolerated hypofractionated DS for hypofractionated, risk volume-adapted PORT was determined to be DS3 (36.4 Gy to the prostate bed and 47.1 Gy to the imaging-defined recurrence in 10 daily fractions). No >G3 events were observed. Transient declines in QOL did not persist through 24 months.Published by Elsevier Inc.