目的:阐明中枢神经系统(CNS)转移对复发时表现状态(PS)的影响,在后续治疗中,以及具有共同表皮生长因子受体(EGFR)突变的肺腺癌患者的生存率。
方法:我们在2015年至2018年期间在日本的21个中心对肺腺癌根治术患者进行了多中心真实世界数据库研究。在每个中心检查EGFR突变状态。
结果:在4181名患者中,1431例接受了具有常见EGFR突变的肺腺癌的完整解剖切除。三百二十名患者经历了疾病复发,78例(24%)发生CNS转移。接受常规辅助化疗的患者的CNS转移明显高于未接受常规辅助化疗的患者(30%vs.20%,P=0.036)。辅助化疗在任何病理阶段均未显著改善无复发生存率(IA2-3期、IB期的调整风险比,II-III分别为1.363、1.287和1.004)。CNS转移在复发时不影响PS。后续治疗,主要由EGFR-酪氨酸激酶抑制剂(TKIs)组成,可以在有或没有中枢神经系统转移的患者中同样给予(96%与94%)。有和没有CNS转移的患者复发后的总生存期相等。
结论:对于EGFR突变的肺腺癌患者,常规辅助化疗的疗效可能有限。CNS转移可能在PS恶化之前在实践中发现,并且可能对后续EGFR-TKIs的依从性和复发后的生存率几乎没有负面影响。在这个辅助TKI治疗的时代,需要进一步的前瞻性观察性研究来阐明CNS转移的最佳治疗方法.
OBJECTIVE: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation.
METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center.
RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis.
CONCLUSIONS: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.