Survival Outcomes in Lung Cancer Patients Newly Diagnosed Through Brain Metastasis Surgery: Impact of Druggable Mutations and Radiotherapy.

Background: Precocious brain metastasis in lung cancer, diagnosed through surgical resection before primary lung cancer detection, represents a unique clinical scenario with limited research. This study aims to investigate the clinical characteristics, prognosis, and the impact of different treatments on survival outcomes in this distinct population.

Materials and methods: We retrospectively analyzed clinical outcomes of lung cancer patients newly diagnosed following brain metastasis decompression surgery in our institute, over a period from July 2012 to May 2023. Patient demographics including gender, age, surgical approach, pathological findings, receipt of radiotherapy, systemic treatment modalities, and presence of druggable mutations were documented. Druggable mutations were defined as actionable genetic alterations (AGAs) detected in patients for which corresponding targeted therapeutic agents were available.

Results: Among 64 patients analyzed, 53 (82.8%) were diagnosed with adenocarcinoma; 38 (59.4%) harbored druggable mutations. There was only one patient with small cell carcinoma in this series. Types of druggable mutations were discussed in the study. The clinical stage was IVB among 38 (59.4%) patients. Forty-nine (76.6%) patients had metastatic brain lesions with number ≦3. Thirty-five (54.7%) patients received post-operative radiotherapy. The cohort's median overall survival (OS) was 19.6 months. Patients with druggable mutations had an OS longer than patients without druggable mutation (46.0 vs 14.5 months, Log rank test p =0.004). Among patients with druggable mutations, we found no difference in characteristics between patients with and without post-operative cranial radiotherapy. Patients receiving post-operative cranial radiotherapy did not show significantly better clinical efficacy than patients without radiotherapy (adjusted hazard ratio: 0.68, 95% confidence interval 0.16 to 2.91).

Conclusion: In patients with precocious brain metastases from lung cancer, the presence of druggable mutations and subsequent targeted therapy significantly extended survival, whereas post-operative brain radiotherapy may not confer additional survival benefits. These findings highlight the importance of molecular profiling and targeted therapy in this unique patient population.