Department of Radiation Oncology, Weill Cornell Medicine/NewYork-Presbyterian, 525 East 68th Street, Box 169, New York, NY, N-046, USA.
Department of Population Health Sciences, Division of Biostatistics, Weill Cornell Medicine/NewYork-Presbyterian, New York, NY, USA.
BMC Cancer. 2023 Aug 22;23(1):781. doi: 10.1186/s12885-023-11278-3.
Ultra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment.
A total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator's discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival.
The SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions.
ClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.
超分割图像引导立体定向体放射治疗（SBRT）越来越多地用于局部前列腺癌的确定性治疗。磁共振成像引导放疗（MRgRT）有助于提高目标和/或危及器官（OAR）的可视化、实时跟踪以及自适应计划的能力，这可能转化为提高靶向性和减少对周围组织的毒性。鉴于 NRG-GU003 研究中比较了术后常规和中度分割的有希望的结果，人们越来越感兴趣地探索超分割术后方案。目前尚不清楚是否可以安全地进行，以及 MRgRT 是否有助于减轻潜在的毒性。Shorter（NCT04422132）是一项前瞻性 II 期随机试验，旨在评估挽救性 MRgRT 在 5 个分数与 20 个分数之间的非劣效性，就 2 年治疗后胃肠道（GI）和泌尿生殖系统（GU）毒性而言。
共有 136 名患者将按照 1:1 的比例随机分为挽救性 MRgRT 5 个分数组或 20 个分数组，采用随机分组。根据基线扩展前列腺癌指数综合（EPIC）肠和尿域评分以及淋巴结治疗和雄激素剥夺治疗（ADT），对患者进行分层。接受 5 个分数的患者将在 2 周内接受总共 32.5Gy，接受 20 个分数的患者将在 4 周内接受总共 55Gy，无论是否有淋巴结覆盖（2 周内 25.5Gy 和 4 周内 42Gy）和 ADT ，根据研究者的判断。主要终点是 EPIC 肠和尿域的变化分数。变化分数将反映 2 年评分减去治疗前（基线）评分。次要终点包括安全性终点，包括治疗完成后 3、6、12 和 60 个月时 GI 和 GU 症状的变化，以及疗效终点，包括进展时间、前列腺癌特异性生存和总生存。
Shorter 试验是第一个比较挽救性 MRgRT 中超高分割和分割与分割的毒性的随机 II 期试验。主要假设是，与 20 个分数的挽救性 MRgRT 相比，5 个分数的挽救性 MRgRT 不会显著增加 GI 和 GU 毒性。
ClinicalTrials.gov 标识符：NCT04422132。注册日期：2020 年 6 月 9 日。
