影像引导的风险体积适应性术后放射治疗第一阶段试验
A Phase 1 Trial of Image Guided Risk Volume-Adapted Postprostatectomy Radiation Therapy
DOI 原文链接
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影响因子:6.5
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
DOI:
10.1016/j.ijrobp.2024.09.048
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患者中，利用风险体积适应的高分割比例放疗（PORT）所能耐受的最紧缩剂量方案（DS）。次要终点包括生化无进展生存期及生活质量（QOL）。患者接受三种等效剂量方案（DS1：20次分次，DS2：15次分次，DS3：10次分次），剂量在影像定义的局部复发部位（等效剂量73 Gy_3，以2 Gy分次计算）递增，而对前列腺床其他区域则剂量递减（等效剂量48 Gy_3，以2 Gy分次计算）。剂量递增遵循标准的3+3设计，最大耐受高分割比例方案（hypofractionated DS）达到最大扩展，扩展组为6例。剂量限制性毒性定义为在PORT完成后21天内持续超过4天的Common Terminology Criteria for Adverse Events v.4.0 三级（G3）毒性，或之后出现的G4期胃肠道（GI）或泌尿系统毒性。通过扩展短表（Expanded Prostate Cancer Index Composite）对QOL在24个月内进行纵向评估。2018年1月至2023年12月，共治疗15例患者（DS1：3例，DS2：3例，DS3：9例），中位随访期48个月。任何剂量方案均未观察到剂量限制性毒性，故在DS3方案上进行扩展。24个月时G3级胃肠道和泌尿系统毒性的累计发生率分别为7%和9%，未见G4事件。最常见为短暂的G2+级急性胃肠道毒性。QOL在随访期间在排尿失禁、胃肠和性功能方面短暂下降，但在24个月时已恢复至基线水平。生化无进展生存率在24和60个月均为91%。最大耐受剂量的高分割比例方案为DS3（10个每日剂次中，前列腺床为36.4 Gy，影像定义复发区域为47.1 Gy）。未观察到G3以上事件。QOL的短暂下降未持续超过24个月。由Elsevier Inc.发表。
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.