局部前列腺癌两次分次立体定向放疗（SABR）后急性毒性与早期前列腺特异抗原反应——SABR-Dual试验初步报告

SABR-Dual是一项III期临床试验，包含初期的I期安全性队列，采用两次分次立体定向放射治疗（SABR），可选择性使用基于磁共振成像（MRI）的病灶增强，使用直肠周隔离剂，针对局部前列腺癌。此次为I期非随机队列的初步报告。受试者为中低危险（FIR）或低风险前列腺腺癌，腺体容积<80 cc。所有患者在模拟前均植入放射造影水凝胶隔离剂和定位标记（计算机断层扫描与3特斯拉T2加权MRI）。临床靶区包括整个前列腺，对于FIR患者，增加精索1-2厘米。计划靶区（PTV）在靶区基础上扩展2毫米，处方剂量为PTV-前列腺27 Gy，PTV-精索23 Gy，可选同时增强MRI定义的优势病变30 Gy。主要终点为基于扩展前列腺癌指标（EPIC-26）、国际前列腺症状评分（IPSS）和男性性健康问卷的患者报告生活质量在3个月的变化。次要终点包括6个月的生活质量、急性毒性（依据CTCAE v5.0）及早期前列腺特异抗原（PSA）反应。结果显示，在20名I期队列患者中，95 %为FIR疾病，50 %接受同时增强。随访中位数为8个月，3个月时在尿失禁、尿阻、肠道、性功能和激素相关领域分别观察到1/20（5 %）、6/20（30 %）、2/20（10 %）、4/20（20 %）和5/20（25 %）的最小临床意义变化。IPSS平均升高1 ± 5.4分，男性感健康问卷得分下降1.8 ± 6.5分。Grade 2及以上的尿路和肠道毒性发生率分别为10 %和0 %，无Grade ≥3毒性。最后随访中PSA平均下降70.4 % ± 17.7 %。该2次分次SABR方案结合直肠隔离剂是一种安全的超高剂量放疗策略，毒性较低。更长期的疗效和与传统5次分次SABR的直接比较正在SABR-Dual的III期随机试验中进行。

SABR-Dual is a phase-III trial with an initial phase-I safety cohort, of 2-fraction stereotactic radiotherapy (SABR) with optional magnetic resonance imaging (MRI)-based focal boost, using peri-rectal spacing, for localized prostate cancer. This represents the initial report from the phase-I non-randomized cohort.Subjects had favorable intermediate risk (FIR) or low risk prostate adenocarcinoma, and gland volume <80 cc. All underwent radiopaque hydrogel spacer and fiducial marker placement before simulation (computed tomography and 3-tesla T2 MRI). The clinical target volume included the entire prostate, and in FIR patients, 1-2 cm of seminal vesicle. A 2-mm expansion was applied for planning target volume (PTV), and a dose of 27 Gy was prescribed to the PTV-prostate, 23 Gy to the PTV-seminal vesicle, with an optional 30 Gy simultaneous boost to an MRI-defined dominant lesion. Primary endpoint was 3-month patient-reported changes in quality of life based on the Expanded Prostate Cancer Index Composite-26, International Prostate Symptom Score, and Sexual Health Inventory for Men questionnaires. Secondary endpoints were 6-month quality of life, acute toxicity (using Common Terminology Criteria for Adverse Events version 5.0) and early Prostate specific antigen (PSA) response.Among the 20 patients in the phase-I cohort, 95% had FIR disease, and 50% received a simultaneous boost. At median follow-up of 8 months, a 3-month minimally clinically important change occurred in 1/20 (5%), 6/20 (30%), 2/20 (10%), 4/20 (20%), and 5/20 (25%) in urinary incontinence, urinary obstructive, bowel, sexual, and hormonal domains. There was a mean increase of 1 ± 5.4 in International Prostate Symptom Score and decrease of 1.8 ± 6.5 in Sexual Health Inventory for Men scores. Rates of grade 2 urinary and bowel toxicity were 10% and 0%, respectively, with no grade ≥3 toxicities. Mean PSA decrease at last follow-up was 70.4% ± 17.7%.This generalizable protocol of 2-fraction prostate SABR using peri-rectal spacing is a safe approach for ultra-hypofractionated dose-escalation, with minimal acute toxicity. Longer-term outcomes and direct comparison with standard 5-fraction SABR are being studied in the phase-III randomized portion of SABR-Dual.