2049 - Cranial Radiotherapy and Local Fraction Dose for Treatment-Naive EGFR-Mutant NSCLC with Brain Metastases on First-Line-3rd-Generation TKIs, Stratified by Lung-molGPA: A Multi-Center Retrospective Analysis
Presenter(s)
G. Deng1, and Z. Li2; 1Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences,, Ji Nan, Shandong, China, 2SHANDONG CANCER HOSPITAL AND INSTITUTE, JINAN, China
Purpose/Objective(s): Third-generation EGFR-TKIs have shown strong effectiveness in treating brain metastases in patients with EGFR-mutant non-small cell lung cancer. However, the best approach for cranial radiotherapy(RT) and the appropriate fractionation dose are still under discussion. We assessed the survival outcomes of various cranial RT methods and local RT fraction doses, categorized by the lung-molGPA index.
Materials/Methods: We conducted a retrospective analysis of 373 patients from multiple centers with EGFR-mutant lung adenocarcinoma and newly diagnosed brain metastases who received first-line third-generation EGFR-TKIs. Patients were divided based on their cranial RT strategies: whole-brain radiotherapy, local RT, and simultaneous integrated boost. A specific subgroup analysis was performed on the local RT group based on the fraction dose (<5Gy vs. =5Gy per fraction). Survival outcomes, including overall survival(OS) and intracranial progression-free survival(iPFS), were estimated using the Kaplan-Meier method and stratified by lung-molGPA scores.
Results: Among the RT strategies, OS significantly differed (p=0.0011), with local RT demonstrating the most favorable OS compared to SIB and WBRT. No significant difference was observed in overall iPFS (p=0.1699). In the high lung-molGPA prognostic group, the OS benefit of local RT and SIB over WBRT remained statistically significant (p=0.0084). In the subgroup analysis strictly limited to patients receiving local RT, no significant overall OS difference was found between the <5Gy and =5Gy fraction dose groups (p=0.8302). However, a significant survival crossover was observed upon lung-molGPA stratification: in the low lung-molGPA prognostic group, the =5Gy fraction dose yielded a significantly superior OS (p=0.0253), whereas in the high lung-molGPA group, the <5Gy fraction dose provided a significantly better OS (p=0.0392). Furthermore, within this local RT cohort, the <5Gy fraction dose group exhibited significantly superior overall iPFS compared to the =5Gy group (p=0.0070).
Conclusion: For patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM treated with first-line third-generation TKIs, local RT yields a superior OS compared to WBRT. Crucially, the optimal fraction dose for local RT is highly dependent on baseline prognosis: a single fraction dose of =5Gy maximizes OS in patients with low lung-molGPA scores, while a <5Gy dose significantly prolongs OS in those with high lung-molGPA scores, alongside providing overall superior intracranial control . These multicenter findings highlight the necessity of individualized, lung-molGPA-guided radiotherapy dose prescription to achieve optimal synergistic efficacy with third-generation EGFR-TKIs.