Agrawal Namita, Shireman Jack M, Shiue Kevin, Kamer Aaron, Boyd LaKeisha, Zang Yong, Mukherjee Neel, Miller James, Kulwin Charles, Cohen-Gadol Aaron, Payner Troy, Lin Chih-Ta, Savage Jesse J, Lane Brandon, Bohnstedt Bradley, Lautenschlaeger Tim, Saito Naoyuki, Shah Mitesh, Watson Gordon, Dey Mahua
Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indianapolis, USA.
Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
Neurooncol Pract. 2024 May 8;11(5):593-603. doi: 10.1093/nop/npae043. eCollection 2024 Oct.
Stereotactic radiosurgery (SRS) following surgical resection is the standard of care for patients with symptomatic oligo brain metastasis (BM), however, it is associated with 10-15% local failure. Targeting a resection cavity is imprecise, thus preoperative radiosurgery where the target is well-defined may be superior, however, the efficacy of preoperative SRS has not yet been tested in a clinical trial.
We conducted a phase 2, single-arm trial of preoperative SRS followed by surgical resection in patients with 1-4 symptomatic oligo BMs (NCT03398694) with the primary objective of measuring 6-month local control (LC). SRS was delivered to all patients utilizing a gamma knife or linear accelerator as per RTOG-9005 dosing criteria [Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. . 2000;47(2):291-298] based on tumor diameter with the exception that the largest lesion diameter treated was 5 cm with 15 Gy with all SRS treatment given in single fraction dosing.
The trial screened 50 patients, 48 patients were treated under the protocol and 32 patients completed the entire follow-up period. Of all the patients who completed the follow-up period, the primary endpoint of 6-month LC was 100% (95% CI: 0.891-1.000; = .005). Secondary endpoints, presented as medians, were overall survival (17.6 months), progression-free survival (5.3 months), distant in-brain failure (40.8% at 1 year), leptomeningeal failure (4.8% at 1 year), and radiation necrosis (7.7% at 1 year).
Our data confirms superior local control in patients who received preoperative SRS when compared to historical controls. Further study with a larger randomized cohort of patients is warranted to fully understand the benefits of preoperative SRS.
手术切除后进行立体定向放射外科治疗（SRS）是有症状的寡转移脑转移瘤（BM）患者的标准治疗方法，然而，其局部失败率为10%-15%。针对切除腔进行治疗并不精确，因此术前放射外科治疗（此时靶区明确）可能更具优势，但是术前SRS的疗效尚未在临床试验中得到验证。
我们开展了一项2期单臂试验，对1-4个有症状的寡转移BM患者先进行术前SRS，然后进行手术切除（NCT03398694），主要目的是评估6个月时的局部控制率（LC）。根据RTOG-9005剂量标准[Shaw E, Scott C, Souhami L等。复发性既往接受过照射的原发性脑肿瘤和脑转移瘤的单次剂量放射外科治疗：RTOG协议90-05的最终报告。. 2000;47(2):291-298]，使用伽玛刀或直线加速器对所有患者进行SRS治疗，依据肿瘤直径确定剂量，唯一的例外是最大治疗病灶直径为5 cm，给予15 Gy，所有SRS治疗均采用单次剂量给药。
该试验筛查了50例患者，48例患者按照方案接受了治疗，32例患者完成了整个随访期。在所有完成随访期的患者中，6个月LC的主要终点为100%（95%CI：0.891-1.000； = .005）。次要终点以中位数表示，分别为总生存期（17.6个月）、无进展生存期（5.3个月）、脑内远处失败率（1年时为40.8%）、软脑膜失败率（1年时为4.8%）以及放射性坏死率（1年时为7.7%）。
我们的数据证实，与历史对照相比，接受术前SRS的患者局部控制效果更佳。有必要对更大规模的随机患者队列进行进一步研究，以全面了解术前SRS的益处。
