Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota.
Int J Radiat Oncol Biol Phys. 2014 Jul 1;89(3):509-17. doi: 10.1016/j.ijrobp.2014.03.012.
To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury.
Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer.
At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm(3) (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010).
Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.
报告在 5 个分割立体定向体放射治疗（SBRT）局部前列腺癌的最高剂量水平下，发生孤立的严重直肠毒性病例；并合理测试潜在的因果机制，以指导未来的研究和实验，帮助减轻或完全避免这种严重的肠道损伤。
对 2006 年至 2011 年期间纳入的 91 例局部前列腺癌 SBRT 剂量递增（45、47.5 和 50 Gy 分 5 次）的 1/2 期临床试验的临床和治疗计划数据进行了分析。
在最高剂量水平，6.6%的治疗患者（91 例中有 6 例）发生了高级别直肠毒性，其中 5 例需要结肠造口术。3 级以上的迟发性直肠毒性与直肠壁接受 50 Gy >3 cm3 的体积（P<.0001）和 39 Gy 治疗的直肠壁>35%周长（P=.003）呈强烈相关。2 级以上的急性直肠毒性与直肠壁接受 24 Gy >50%周长的治疗（P=.010）显著相关。
在考虑将 SBRT 高剂量用于治疗肠结构附近的肿瘤，包括前列腺癌时，需要谨慎。已经确定了基于生理原理的阈值剂量限制，如果得到尊重，可以最大限度地降低严重直肠毒性的风险。
