J Cancer 2020; 11(24):7283-7290. doi:10.7150/jca.46462

Research Paper

Metachronous Brain Metastasis in patients with EGFR-mutant NSCLC indicates a worse prognosis

Wen Ouyang1*, Jing Yu1*, Yan zhou1, Yu Xu1, Jie Li1, Jun Gong1, Junhong Zhang1✉, Conghua Xie1,2,3✉

1. Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.
2. Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.
3. Hubei Clinical Cancer Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
*Both authors contributed equally as co-first authors.

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Ouyang W, Yu J, zhou Y, Xu Y, Li J, Gong J, Zhang J, Xie C. Metachronous Brain Metastasis in patients with EGFR-mutant NSCLC indicates a worse prognosis. J Cancer 2020; 11(24):7283-7290. doi:10.7150/jca.46462. Available from https://www.jcancer.org/v11p7283.htm

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Purpose: NSCLC patients with EGFR mutation were associated with high incidence of brain metastasis (BM). BM could be grouped by the time of occurrence, including synchronous BM at initial diagnosis and metachronous BM during disease course. The primary aim of the study was to investigate the survival of patients with metachronous BM.

Methods: A total of 99 EGFR-mutant advanced NSCLC patients in our institute between 2012 and 2018 were grouped into synchronous BM and metachronous BM. Comparisons of OS were performed based on BM status. The independent prognostic factors of OS were investigated, and extracranial and intracranial PFS were further analyzed.

Results: Patients with metachronous BM (mOS: 22.1 months) had poorer outcomes than synchronous BM (mOS: 30.3 months) (P=0.016). Moreover, multivariate analysis indicated that BM status (P=0.015), local therapy for BM (P=0.013) and subsequent treatment of Osimertinib (P=0.008) impact significantly on OS. Significantly, the proportion of local therapy for BM had no difference between patients with synchronous and metachronous BM. And patients with metachronous BM harbored a more favorable prognostic factor (higher proportion of subsequent Osimertinib treatment), but also harbored a poorer prognostic factor (metachronous BM), which confirmed BM status was the most significant prognostic factor of OS. At last, results of extracranial and intracranial PFS indicated that patients with metachronous BM tended to have a higher risk of intracranial disease progression.

Conclusions: Patients developing metachronous BM during EGFR-TKIs treatment have worse outcomes than synchronous BM. Our findings suggested that the patients with metachronous BM should receive more aggressive treatments.

Keywords: non-small cell lung cancer, epidermal growth factor receptor, brain metastases, synchronous, metachronous