McClelland Shearwood, Lautenschlaeger Tim, Zang Yong, Hanna Nasser H, Shiue Kevin, Kamer Aaron P, Agrawal Namita, Ellsworth Susannah G, Rhome Ryan M, Watson Gordon A
Department of Radiation Oncology, Indiana University School of Medicine, 535 Barnhill Drive, RT 041, Indianapolis, IN 46202, US.
Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, US.
Rep Pract Oncol Radiother. 2020 Jul-Aug;25(4):500-506. doi: 10.1016/j.rpor.2020.04.007. Epub 2020 Apr 23.
Up to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates.
This study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0-2 cm lesions, 14 Gy for 2.1-3 cm lesions, and 12 Gy for 3.1-4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90-05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria.
This study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population.
Clinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).
接受免疫检查点抑制剂（ICI）治疗并同时接受立体定向放射外科治疗（SRS）的脑转移患者中，高达20%会出现症状性放射性坏死。本研究的目的是评估免疫治疗脑转移瘤的放射外科剂量降低（RADREMI）对6个月症状性放射性坏死率的影响。
本研究是一项前瞻性单臂I期试验性研究，将招募在SRS前30天内接受ICI治疗的脑转移患者。所有患者将接受RADREMI剂量方案治疗，即0 - 2厘米的病灶给予18 Gy的SRS剂量，2.1 - 3厘米的病灶给予14 Gy，3.1 - 4厘米的病灶给予12 Gy。所有患者将接受为期6个月的症状性放射性坏死监测（定义为需要使用类固醇药物治疗和/或手术干预且影像学表现与放射性坏死相符的6个月临床症状发生率）以及6个月的局部控制情况监测。我们预计RADREMI剂量方案将显著降低同时进行SRS + ICI治疗时的症状性放射性坏死率，且不会显著牺牲目前RTOG 90 - 05 SRS剂量方案所取得的局部控制效果。局部控制将根据神经肿瘤学疗效评估（RANO）标准进行定义。
本研究是首个前瞻性试验，旨在研究降低剂量的SRS联合ICI治疗脑转移瘤的安全性。这些研究结果应为未来针对该患者群体的RADREMI剂量方案多机构协作疗效试验提供丰富的依据。
Clinicaltrials.gov标识符：NCT04047602（注册日期：2019年7月25日）
