Introduction: Patients with brain metastases (BMs) arising from EGFR‐mutated and anaplastic lymphoma kinase gene (ALK)‐rearranged NSCLC have a favorable prognosis compared with patients with non–oncogene‐addicted NSCLC, emphasizing the importance of minimizing toxicities such as the cognitive sequelae of whole brain radiation therapy (WBRT). Although radiosurgery without WBRT is the preferred strategy for one to three BMs, this paradigm remains controversial for patients with multiple BMs. Methods: We reviewed the cases of patients with EGFR‐mutated and ALK‐rearranged NSCLC presenting to our cancer center between 2008 and 2017 and included only patients receiving treatment to four or more BMs in a single radiosurgery session. Results: We identified 35 patients with a median follow‐up of 4.1 years. The maximum number of BMs treated in a single radiosurgery session ranged from four to 26 (median number of BM treated per radiosurgery course: 6), and in total over all courses the number ranged from four to 47 (median: 10). The median survival was 3.0 years (4.2 for ALK‐rearranged NSCLC; 2.4 for EGFR‐mutated NSCLC) from the diagnosis of BM, and survival was comparable regardless of number of radiosurgery courses, number of BMs treated in total, or number of BMs treated in a single radiosurgery session. The mean hippocampal and whole‐brain doses were exceedingly low even for patients receiving treatment to more than 10 BMs (1.2 and 0.8 Gy, respectively). Radiosurgery was well tolerated overall and the 5‐year rate of freedom from neurologic death was 84%. The 5‐year rate of freedom from WBRT was 97%. Conclusions: Radiosurgery for multiple BMs is controversial, yet patients with EGFR‐mutated and ALK‐rearranged NSCLC may be uniquely suited to benefit from this approach. These results support single and multiple courses of radiosurgery without WBRT for patients with oncogene‐addicted NSCLC with four or more BMs.

中文翻译：

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对致癌基因成瘾的非小细胞肺癌多发脑转移进行放射外科治疗的优异结果

简介：与非癌基因成瘾的 NSCLC 患者相比，由 EGFR 突变和间变性淋巴瘤激酶基因 (ALK) 重排的 NSCLC 引起的脑转移 (BMs) 患者具有良好的预后，强调最小化毒性的重要性，例如认知功能障碍全脑放射治疗 (WBRT) 的后遗症。尽管没有 WBRT 的放射外科手术是 1 到 3 个 BM 的首选策略，但这种模式对于多个 BM 的患者仍然存在争议。方法：我们回顾了 2008 年至 2017 年期间在我们癌症中心就诊的 EGFR 突变和 ALK 重排 NSCLC 患者的病例，并且仅包括在一次放射外科治疗中接受 4 个或更多 BM 治疗的患者。结果：我们确定了 35 名患者，中位随访时间为 4.1 年。单次放射外科治疗的最大 BM 数量范围为 4 到 26（每个放射外科治疗的 BM 中位数：6），并且在所有课程中，总数范围为 4 到 47（中位数：10）。从诊断 BM 算起，中位生存期为 3.0 年（ALK 重排 NSCLC 为 4.2 年；EGFR 突变的 NSCLC 为 2.4 年），无论放射外科疗程数、BM 治疗总数或 BM 治疗数如何，生存期均具有可比性在一次放射外科治疗中。即使患者接受超过 10 BM（分别为 1.2 和 0.8 Gy）的治疗，平均海马和全脑剂量也非常低。放射外科治疗总体耐受性良好，5 年无神经系统死亡率为 84%。5 年免于 WBRT 的率为 97%。结论：多个 BM 的放射外科手术是有争议的，但 EGFR 突变和 ALK 重排的 NSCLC 患者可能特别适合从这种方法中受益。这些结果支持对具有 4 个或更多 BM 的癌基因成瘾性 NSCLC 患者进行单次和多次放射外科手术，无需 WBRT。