前列腺切除术后前列腺窝立体定向放疗的 1 期临床试验。
Phase 1 Trial of SBRT to the Prostate Fossa After Prostatectomy.
机构信息
Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California.
Department of Preventative Medicine, University of Southern California Keck School of Medicine, Los Angeles, California.
出版信息
Int J Radiat Oncol Biol Phys. 2019 May 1;104(1):50-60. doi: 10.1016/j.ijrobp.2018.12.047. Epub 2018 Dec 31.
PURPOSE
The primary objective was to evaluate the maximum tolerated dose (within 10 weeks after treatment) associated with increasing hypofractionation to the prostate fossa (PF). We hypothesized that escalating the dose per fraction (fx) to the PF would have acceptable toxicity.
MATERIALS AND METHODS
Tested dose levels (DLs) were 3.6 Gy × 15 fx (DL1); 4.7 Gy × 10 fx (DL2); and 7.1 Gy × 5 fx (DL3). Escalation followed a 6 + 6 rules-based design with 12 patients required at the maximum tolerated dose. Dose-limiting toxicity was defined as grade (G) ≥3, gastrointestinal (GI) or genitourinary (GU) toxicity by National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Patients completed quality-of-life questionnaires.
RESULTS
Twenty-four patients with indications for adjuvant or salvage radiation therapy (RT) enrolled (6 at DL1 and 2; 12 at DL3). All patients had at least 6 months of follow-up (median follow-up, 14.1 months). Four patients received concurrent androgen deprivation therapy. No G ≥ 3 GI or GU toxicity was seen at any DL; 2 of 6 patients in the DL1 group, 3 of 6 in DL2, and 7 of 12 in DL3 experienced G2 GI toxicity during RT. Except in 1 patient, all acute G2 GI toxicity resolved by 10 weeks. Three of 12 patients reported an increase to G1 and G2 GU toxicity in the 2 weeks after RT in groups DL1 and DL2 and 1 of 12 patients in DL3. At week 2 after RT, decline in the 26-item Expanded Prostate Cancer Index Composite bowel domain met criteria for a minimally important difference in 71% of patients. At week 10, 1 of 6, 2 of 6, and 7 of 11 patients at DLs 1, 2, and 3, respectively, still met minimally important difference criteria. International Prostate Symptom Scores worsened 2 weeks after treatment but improved by 6 to 10 weeks.
CONCLUSIONS
Dose escalation up to 7.1 Gy × 5 fx to the PF was completed without acute G ≥ 3 toxicity. There was transient G2 rectal toxicity at all DLs during and immediately after RT. We must perform long-term follow-up and assessment of late toxicity of SBRT to the PF.
目的
主要目的是评估与前列腺窝（PF）的分次剂量递增相关的最大耐受剂量（治疗后 10 周内）。我们假设递增 PF 中的分次剂量（fx）会产生可接受的毒性。
材料与方法
测试剂量水平（DL）分别为 3.6 Gy×15 fx（DL1）；4.7 Gy×10 fx（DL2）；和 7.1 Gy×5 fx（DL3）。按照基于 6+6 规则的设计进行递增，最大耐受剂量需要 12 例患者。剂量限制毒性定义为国家癌症研究所不良事件通用术语标准（版本 4.03）的 G≥3 级、胃肠道（GI）或泌尿生殖系统（GU）毒性。患者完成生活质量问卷。
结果
24 例有辅助或挽救性放疗（RT）适应证的患者入组（DL1 组 6 例，DL3 组 2 例）。所有患者的随访时间至少为 6 个月（中位随访时间 14.1 个月）。4 例患者接受了同期雄激素剥夺治疗。任何 DL 均未见 G≥3 级 GI 或 GU 毒性；DL1 组 6 例中有 2 例，DL2 组 6 例中有 3 例，DL3 组 12 例中有 7 例在 RT 期间出现 G2 级 GI 毒性。除 1 例患者外，所有急性 G2 级 GI 毒性均在 10 周内缓解。DL1 和 DL2 组各有 3 例和 1 例患者在 RT 后 2 周内报告 GU 毒性增加至 G1 和 G2 级，DL3 组有 1 例患者报告 G2 级 GU 毒性。在 RT 后 2 周，26 项前列腺癌指数综合（Expanded Prostate Cancer Index Composite）肠域评分下降达到了最小有意义差异标准的 71%。在 RT 后 10 周时，DL1、DL2 和 DL3 组的 6 例、6 例和 11 例患者中，分别有 1 例、2 例和 7 例仍符合最小有意义差异标准。国际前列腺症状评分（International Prostate Symptom Score）在治疗后 2 周时恶化，但在 6 至 10 周时改善。
结论
递增至 PF 的 7.1 Gy×5 fx 剂量未出现急性 G≥3 级毒性。在 RT 期间和之后，所有 DL 均出现一过性 G2 级直肠毒性。我们必须进行长期随访和评估 SBRT 对 PF 的迟发性毒性。
Zotero 插件