Abstract：
OBJECTIVE: Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BMs) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations.
METHODS: In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021. We compared survival of patients with and without targetable mutations based on clinical variables and treatment.
RESULTS: Among the 213 patients included, 87 (40.8%) had targetable mutations-primarily EGFR (22.5%)-and 126 (59.2%) did not. Patients with targetable mutations were more often female (63.2%, p <.001) and nonsmokers (58.6%, p <.001); had higher initial lung-molGPA (2.0 vs. 1.5, p <.001) and lower cumulative tumor volume (3.7 vs. 10.6 cm3, p <.001); and received more concurrent (55.2% vs. 36.5%, p =.007) and total (median 3 vs. 2, p <.001) systemic therapies. These patients had lower mortality rates (74.7% vs. 91.3%, p <.001) and risk (HR 0.298 [95%CI 0.190-0.469], p <.001) and longer median overall survival (20.2 vs. 7.4 months, p <.001), including survival ≥ 3 years (p =.001). Survival was best predicted by SRS with tumor resection in patients with non-targetable mutations (HR 0.491 [95%CI 0.318-757], p =.001) and by systemic therapy with SRS for those with targetable mutations (HR 0.124 [95%CI 0.013-1.153], p =.067).
CONCLUSIONS: The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Survival for patients without targetable mutations was longest with SRS and surgical resection. These results inform best practices for managing patients with NSCLC BM based on driver mutation status.
METHODS: In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021. We compared survival of patients with and without targetable mutations based on clinical variables and treatment.
RESULTS: Among the 213 patients included, 87 (40.8%) had targetable mutations-primarily EGFR (22.5%)-and 126 (59.2%) did not. Patients with targetable mutations were more often female (63.2%, p <.001) and nonsmokers (58.6%, p <.001); had higher initial lung-molGPA (2.0 vs. 1.5, p <.001) and lower cumulative tumor volume (3.7 vs. 10.6 cm3, p <.001); and received more concurrent (55.2% vs. 36.5%, p =.007) and total (median 3 vs. 2, p <.001) systemic therapies. These patients had lower mortality rates (74.7% vs. 91.3%, p <.001) and risk (HR 0.298 [95%CI 0.190-0.469], p <.001) and longer median overall survival (20.2 vs. 7.4 months, p <.001), including survival ≥ 3 years (p =.001). Survival was best predicted by SRS with tumor resection in patients with non-targetable mutations (HR 0.491 [95%CI 0.318-757], p =.001) and by systemic therapy with SRS for those with targetable mutations (HR 0.124 [95%CI 0.013-1.153], p =.067).
CONCLUSIONS: The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Survival for patients without targetable mutations was longest with SRS and surgical resection. These results inform best practices for managing patients with NSCLC BM based on driver mutation status.
摘要：
目的：非小细胞肺癌（NSCLC）脑转移瘤（BMs）的靶向治疗方案可与立体定向放射外科（SRS）结合以优化生存期。我们评估了NSCLCBMs的SRS后患者的预后，确定与靶向突变相关的生存轨迹。
方法：在此回顾性时间依赖性分析中，我们分析了2001年至2021年接受1次以上SRS疗程的NSCLC患者的中位总生存期.我们根据临床变量和治疗方法比较了有和没有靶向突变的患者的生存率。
结果：在213名患者中，87（40.8％）具有可靶向突变-主要是EGFR（22.5％）-和126（59.2％）没有。具有靶向突变的患者更常见的是女性（63.2％，p<.001)和不吸烟者(58.6%，p<.001）；初始肺-molGPA较高（2.0vs.1.5，p<.001）和较低的累积肿瘤体积（3.7vs.10.6cm3，p<.001)；并收到更多的并发(55.2%与36.5%,p=.007）和总计（中位数3与2，p<.001）全身治疗。这些患者的死亡率较低（74.7%vs.91.3%,p<.001）和风险（HR0.298[95CI0.190-0.469]，p<.001）和更长的中位总生存期（20.2vs.7.4个月，p<.001),包括生存≥3年（p=.001）。在具有非靶向突变的患者中，通过SRS切除肿瘤可以最好地预测生存率（HR0.491[95CI0.318-757]，p=.001），并通过SRS对具有靶向突变的患者进行全身治疗（HR0.124[95CI0.013-1.153]，p=.067）。
结论：可靶向突变的存在增强了接受SRS治疗的NSCLCBM患者的生存率，特别是与全身疗法一起使用时。在SRS和手术切除的情况下，没有靶向突变的患者的生存期最长。这些结果为基于驱动突变状态管理NSCLCBM患者提供了最佳实践。
方法：在此回顾性时间依赖性分析中，我们分析了2001年至2021年接受1次以上SRS疗程的NSCLC患者的中位总生存期.我们根据临床变量和治疗方法比较了有和没有靶向突变的患者的生存率。
结果：在213名患者中，87（40.8％）具有可靶向突变-主要是EGFR（22.5％）-和126（59.2％）没有。具有靶向突变的患者更常见的是女性（63.2％，p<.001)和不吸烟者(58.6%，p<.001）；初始肺-molGPA较高（2.0vs.1.5，p<.001）和较低的累积肿瘤体积（3.7vs.10.6cm3，p<.001)；并收到更多的并发(55.2%与36.5%,p=.007）和总计（中位数3与2，p<.001）全身治疗。这些患者的死亡率较低（74.7%vs.91.3%,p<.001）和风险（HR0.298[95CI0.190-0.469]，p<.001）和更长的中位总生存期（20.2vs.7.4个月，p<.001),包括生存≥3年（p=.001）。在具有非靶向突变的患者中，通过SRS切除肿瘤可以最好地预测生存率（HR0.491[95CI0.318-757]，p=.001），并通过SRS对具有靶向突变的患者进行全身治疗（HR0.124[95CI0.013-1.153]，p=.067）。
结论：可靶向突变的存在增强了接受SRS治疗的NSCLCBM患者的生存率，特别是与全身疗法一起使用时。在SRS和手术切除的情况下，没有靶向突变的患者的生存期最长。这些结果为基于驱动突变状态管理NSCLCBM患者提供了最佳实践。
