Rangachari Deepa, Yamaguchi Norihiro, VanderLaan Paul A, Folch Erik, Mahadevan Anand, Floyd Scott R, Uhlmann Erik J, Wong Eric T, Dahlberg Suzanne E, Huberman Mark S, Costa Daniel B
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Lung Cancer. 2015 Apr;88(1):108-11. doi: 10.1016/j.lungcan.2015.01.020. Epub 2015 Feb 4.
Brain metastases (BM) are common in non-small-cell lung cancer (NSCLC). However, the baseline incidence and evolution of BM over time in oncogene-driven NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC.
The presence of BM, clinicopathologic data, and tumor genotype were retrospectively compiled and analyzed from a cohort of 381 patients.
We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs. BM were present in 24.4% of EGFR-mutated and 23.8% of ALK-rearranged NSCLCs at the time of diagnosis of advanced disease. This study did not demonstrate a difference in the cumulative incidence of BM over time between the two cohorts (EGFR/ALK cohort competing risk regression [CRR] coefficient of 0.78 [95% CI 0.44-1.39], p=0.41). In still living patients with advanced EGFR-mutated NSCLC, 34.2% had BM at 1 year, 38.4% at 2 years, 46.7% at 3 years, 48.7% at 4 years, and 52.9% at 5 years. In still living patients with advanced ALK-rearranged NSCLC, 23.8% had BM at 1 year, 45.5% at 2 years, and 58.4% at 3 years.
BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by three years of survival with the use of targeted therapies. These data point toward the CNS as an important unmet clinical need in the evolving schema for personalized care in NSCLC.
脑转移（BM）在非小细胞肺癌（NSCLC）中很常见。然而，关于致癌基因驱动的NSCLC中BM的基线发病率及其随时间的演变情况鲜有报道。在本研究中，我们评估了表皮生长因子受体（EGFR）突变或间变性淋巴瘤激酶（ALK）重排的NSCLC患者中BM的发生频率。
回顾性收集并分析了381例患者的BM情况、临床病理数据及肿瘤基因型。
我们确定了86例EGFR突变（90.7%为转移性疾病；85.9%接受了EGFR抑制剂治疗）和23例ALK重排（91.3%为转移性疾病；85.7%接受了ALK抑制剂治疗）的NSCLC患者。在晚期疾病诊断时，24.4%的EGFR突变NSCLC患者和23.8%的ALK重排NSCLC患者存在BM。本研究未显示两个队列之间BM累积发病率随时间的差异（EGFR/ALK队列竞争风险回归[CRR]系数为0.78[95%CI 0.44 - 1.39]，p = 0.41）。在仍存活的晚期EGFR突变NSCLC患者中，1年时34.2%发生BM，2年时38.4%，3年时46.7%，4年时48.7%，5年时52.9%。在仍存活的晚期ALK重排NSCLC患者中，1年时23.8%发生BM，2年时45.5%，3年时58.4%。
BM在晚期EGFR突变或ALK重排的NSCLC中很常见，估计使用靶向治疗三年生存率时超过45%的患者会出现中枢神经系统受累。这些数据表明中枢神经系统是NSCLC个性化治疗不断发展模式中一个重要的未满足临床需求。
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