Clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma.

Objective: To identify clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma (LUAD) and to evaluate survival after brain metastasis.

Methods: Patients who underwent complete resection of stage I-IIIA LUAD between 2011 and 2020 were included. A subset of patients had broad-based panel next-generation sequencing performed on their tumors. Fine-Gray models for the development of brain metastasis were constructed, with death without brain metastasis as a competing risk.

Results: A total of 2660 patients were included. The median duration of follow-up was 71 months (95% confidence interval [CI], 69-73 months). The cumulative incidence of brain metastasis at 10 years was 9.8%. Among patients who developed a brain metastasis, the median time from surgery to brain metastasis was 21 months (interquartile range, 10-42 months). Higher maximum standardized uptake value of the primary tumor, neoadjuvant therapy, lymphovascular invasion, and stage III disease were associated with the development of brain metastasis. Among patients who underwent next-generation sequencing, a multivariable analysis identified neoadjuvant therapy, pathologic stage, and TP53 mutations as associated with development of brain metastasis. The median survival after brain metastasis was 18 months (95% CI, 13-24 months). Better performance status, lack of extracranial metastasis, stereotactic radiosurgery, and targeted therapy were associated with better survival after brain metastasis.

Conclusions: Brain metastasis is common after complete resection of LUAD and often occurs within 2 years. Markers of aggressive tumor biology, including higher maximum standardized uptake value, lymphovascular invasion, and TP53 mutations, and neoadjuvant therapy are associated with brain metastasis.