Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia.
Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia.
Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1254-1262. doi: 10.1016/j.ijrobp.2020.11.009. Epub 2020 Nov 21.
The phase 1 portion of this multicenter, phase 1/2 study of hypofractionated (HypoFx) prostate bed radiation therapy (RT) as salvage or adjuvant therapy aimed to identify the shortest dose-fractionation schedule with acceptable toxicity. The phase 2 portion aimed to assess the health-related quality of life (QoL) of using this HypoFx regimen.
Eligibility included standard adjuvant or salvage prostate bed RT indications. Patients were assigned to receive 1 of 3 daily RT schedules: 56.6 Gy in 20 Fx, 50.4 Gy in 15 Fx, or 42.6 Gy in 10 Fx. Regional nodal irradiation and androgen deprivation therapy were not allowed. Participants were followed for 2 years after treatment with outcome measures based on prostate-specific antigen levels, toxicity assessments (Common Terminology Criteria for Adverse Events, v4.0), QoL measures (the Expanded Prostate Cancer Index Composite [EPIC] and EuroQol EQ-5D instruments), and out-of-pocket costs.
There were 32 evaluable participants, and median follow-up was 3.53 years. The shortest dose-fractionation schedule with acceptable toxicity was determined to be 42.6 Gy in 10 Fx, with most patients (23) treated with this schedule. Grade 3 genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 3 patients and 1 patient, respectively. There was 1 grade 4 sepsis event. Higher dose to the hottest 25% of the rectum was associated with increased risk of grade 2+ GI toxicity; no dosimetric factors were found to predict for GU toxicity. There was a significant decrease in the mean bowel, but not bladder, QoL score at 1 year compared with baseline. Prostate-specific antigen failure occurred in 34.3% of participants, using a definition of nadir plus 2 ng/mL. Metastases were more likely to occur in regional lymph nodes (5 of 7) than in bones (2 of 7). The mean out-of-pocket cost for patients during treatment was $223.90.
We identified 42.6 Gy in 10 fractions as the shortest dose-fractionation schedule with acceptable toxicity in this phase 1/2 study. There was a higher than expected rate of grade 2 to 3 GU and GI toxicity and a decreased EPIC bowel QoL domain with this regimen. Future studies are needed to explore alternative adjuvant/salvage HypoFx RT schedules after radical prostatectomy.
本研究为多中心、1 期/2 期的前列腺床分割放疗（HypoFx）挽救或辅助治疗的 1 期部分，旨在确定具有可接受毒性的最短剂量分割方案。2 期部分旨在评估使用这种 HypoFx 方案的健康相关生活质量（QoL）。
纳入标准包括标准辅助或挽救性前列腺床 RT 适应证。患者被分配接受 3 种每日 RT 方案之一：56.6 Gy 20 次分割、50.4 Gy 15 次分割或 42.6 Gy 10 次分割。不允许进行区域淋巴结照射和雄激素剥夺治疗。治疗后随访 2 年，根据前列腺特异性抗原水平、毒性评估（不良事件通用术语标准，v4.0）、QoL 评估（前列腺癌综合指数扩展量表 [EPIC]和 EuroQol EQ-5D 工具）和自付费用进行评估。
共有 32 名可评估的参与者，中位随访时间为 3.53 年。最短的剂量分割方案为 42.6 Gy 10 次分割，大多数患者（23 例）接受了这种方案治疗。3 例患者发生 3 级泌尿生殖系统（GU）和胃肠道（GI）毒性，1 例患者发生 1 级 4 级败血症事件。更高剂量的 hottest 25%直肠与 2+级 GI 毒性风险增加相关；没有发现剂量学因素可以预测 GU 毒性。与基线相比，1 年时的平均肠道，但不是膀胱，QoL 评分显著下降。使用定义为最低点加 2ng/ml 的方法，有 34.3%的参与者发生前列腺特异性抗原失败。转移更可能发生在区域淋巴结（7 例中有 5 例）而不是骨骼（7 例中有 2 例）。治疗期间患者的平均自付费用为 223.90 美元。
在这项 1 期/2 期研究中，我们确定了 42.6 Gy 10 次分割是毒性可接受的最短剂量分割方案。这种方案的 GU 和 GI 毒性发生率高于预期，且 EPIC 肠道 QoL 域降低。需要进一步研究来探索根治性前列腺切除术后辅助/挽救性 HypoFx RT 的替代分割方案。
