Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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%.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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%.
CONCLUSIONS: 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.
摘要：
目的：SABR-Dual是一项III期试验，初始I期安全性队列，具有可选的基于MRI的局灶性增强的两部分立体定向放射治疗（SABR），使用直肠周围间距，局部前列腺癌.这代表来自I期非随机队列的初始报告。
方法：受试者具有有利的中等风险（FIR）或低风险（LR）前列腺腺癌，和腺体体积<80cc。在模拟(CT和3-teslaT2MRI)之前,全部经历不透射线的水凝胶间隔物和基准标记物放置。临床目标体积包括整个前列腺，在FIR患者中，精囊1-2cm（SV）。应用2mm扩展计划目标体积(PTV)，给PTV前列腺开了27Gy的剂量，23Gy到PTV-SV，对MRI定义的主要病变进行可选的30Gy同步增强（SIB）。主要终点是根据EPIC-26、IPSS、和SHIM问卷。次要终点是6个月的生活质量，急性毒性（使用CTCAEv5）和早期PSA反应。
结果：在I期队列的20名患者中，95%患有FIR病,50%收到SIB。在中位随访8个月时，3个月的最低临床重要变化发生在1/20（5％），6/20（30%），2/20（10%），4/20（20%），和5/20（25％）的尿失禁，尿路梗阻,肠,性,和荷尔蒙领域。IPSS平均增加1±5.4，SHIM评分平均减少1.8±6.5。2级泌尿和肠道毒性的发生率为10%和0%，分别,无≥3级毒性。末次随访时PSA平均下降70.4%±17.7%。
结论：这种使用直肠周围间距的两部分前列腺SABR的可推广方案是超小分割剂量递增的安全方法，具有最小的急性毒性。在SABR-Dual的III期随机部分中，正在研究长期结果和与标准5-分数SABR的直接比较。
方法：受试者具有有利的中等风险（FIR）或低风险（LR）前列腺腺癌，和腺体体积<80cc。在模拟(CT和3-teslaT2MRI)之前,全部经历不透射线的水凝胶间隔物和基准标记物放置。临床目标体积包括整个前列腺，在FIR患者中，精囊1-2cm（SV）。应用2mm扩展计划目标体积(PTV)，给PTV前列腺开了27Gy的剂量，23Gy到PTV-SV，对MRI定义的主要病变进行可选的30Gy同步增强（SIB）。主要终点是根据EPIC-26、IPSS、和SHIM问卷。次要终点是6个月的生活质量，急性毒性（使用CTCAEv5）和早期PSA反应。
结果：在I期队列的20名患者中，95%患有FIR病,50%收到SIB。在中位随访8个月时，3个月的最低临床重要变化发生在1/20（5％），6/20（30%），2/20（10%），4/20（20%），和5/20（25％）的尿失禁，尿路梗阻,肠,性,和荷尔蒙领域。IPSS平均增加1±5.4，SHIM评分平均减少1.8±6.5。2级泌尿和肠道毒性的发生率为10%和0%，分别,无≥3级毒性。末次随访时PSA平均下降70.4%±17.7%。
结论：这种使用直肠周围间距的两部分前列腺SABR的可推广方案是超小分割剂量递增的安全方法，具有最小的急性毒性。在SABR-Dual的III期随机部分中，正在研究长期结果和与标准5-分数SABR的直接比较。
