Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan,
Oncology. 2020;98(7):460-467. doi: 10.1159/000506368. Epub 2020 Mar 27.
Brain metastases (BM) are one of the strongest negative prognostic factors in patients with non-small cell lung cancer (NSCLC). Molecularly targeted agents are standard of care for NSCLC patients with a driver mutation; however, their efficacy in patients with BM is not fully understood because patients with BM are usually excluded from clinical studies. This study investigated the current management and outcomes of newly diagnosed NSCLC patients with BM in Japanese clinical practice, focusing on their driver mutation status.
We enrolled newly diagnosed, treatment-naïve NSCLC patients with BM between January 2012 and December 2015 from 4 institutions in Japan. The medical records of each patient were retrospectively reviewed, and the treatment details and outcomes were evaluated.
In total, 203 patients with BM were enrolled in this study and 73 (36%) were neurologically symptomatic. Regarding initial treatment, 110 patients (54%) received local therapy, including radiotherapy and surgery, whereas 77 (38%) received systemic therapy. The median overall survival (OS) was 14.3 months for all patients, and it was significantly longer among patients with a driver mutation (28.9 months; 95% confidence interval [CI], 20.9-41.0) than among patients without a driver mutation (9.9 months; 95% CI, 7.0-13.4) (hazard ratio [HR] 0.39; 95% CI, 0.27-0.57; p < 0.001). Multivariate analysis identified performance status (HR 1.78; 95% CI, 1.16-2.72; p = 0.009) and driver mutation status (HR 0.27; 95% CI, 0.17-0.44; p < 0.001) as significant prognostic factors. No significant difference in OS was noted according to the type of initial treatment, i.e., local versus systemic.
The median OS of patients with a driver mutation was longer than 2 years, even of patients with BM, and it was significantly longer than that of patients without a driver mutation. Driver mutation status, in addition to performance status, was a significant prognostic factor in NSCLC patients with BM.
脑转移（BM）是非小细胞肺癌（NSCLC）患者最强的负面预后因素之一。对于有驱动基因突变的 NSCLC 患者，分子靶向药物是标准治疗方法；然而，由于 BM 患者通常被排除在临床试验之外，因此他们的疗效并不完全清楚。本研究在日本临床实践中调查了新诊断的 NSCLC 合并 BM 患者的当前管理和结果，重点关注其驱动基因突变状态。
我们从日本的 4 家机构招募了 2012 年 1 月至 2015 年 12 月期间新诊断、未经治疗的 NSCLC 合并 BM 患者。回顾性审查每位患者的病历，并评估治疗细节和结果。
本研究共纳入 203 例 BM 患者，其中 73 例（36%）有神经系统症状。关于初始治疗，110 例（54%）患者接受局部治疗，包括放疗和手术，77 例（38%）患者接受全身治疗。所有患者的中位总生存期（OS）为 14.3 个月，有驱动基因突变的患者明显更长（28.9 个月；95%置信区间 [CI]，20.9-41.0），无驱动基因突变的患者为 9.9 个月；95% CI，7.0-13.4）（风险比 [HR] 0.39；95% CI，0.27-0.57；p < 0.001）。多变量分析确定表现状态（HR 1.78；95% CI，1.16-2.72；p = 0.009）和驱动基因突变状态（HR 0.27；95% CI，0.17-0.44；p < 0.001）为显著预后因素。根据初始治疗的类型，即局部与全身，OS 无显著差异。
有驱动基因突变的患者的中位 OS 超过 2 年，即使是 BM 患者，也明显长于无驱动基因突变的患者。除了表现状态外，驱动基因突变状态是 NSCLC 合并 BM 患者的重要预后因素。
