ArticleTherapeutic advances in medical oncology2026
Lung-molGPA may stratify the prognostic impact of TP53 co-mutation in EGFR-mutant lung adenocarcinoma with brain metastases: a multi-center retrospective analysis.
Article in Therapeutic advances in medical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The optimal approach to treatment intensification for epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with brain metastases remains a topic of debate, especially in the context of high-risk molecular features such as TP53 co-mutation. The extent to which baseline clinical risk influences treatment efficacy is yet to be determined. Objectives: We aim to systematically evaluate the prognostic significance of EGFR/TP53 co-mutations in treatment-naïve patients with lung adenocarcinoma and newly diagnosed brain metastases. Design: This study enrolled 218 treatment-naïve patients with EGFR-mutant lung adenocarcinoma and brain metastases who received first-line third-generation EGFR-tyrosine kinase inhibitors (TKIs). Treatment effects were evaluated using interaction models stratified by Lung-molGPA scores. Stratification: Group A (Lung-molGPA 1-2) versus Group B (Lung-molGPA 2.5-4). Methods: Within each group, the influence of TP53 co-mutations on survival was analyzed. Additionally, among patients with TP53 co-mutations, the effects of cranial radiotherapy (CRT) and treatment with either third-generation EGFR-TKIs monotherapy or third-generation EGFR-TKIs combined with chemotherapy on overall survival (OS) were further investigated, taking into account the Lung-molGPA scores. Results: The Lung-molGPA significantly influenced the prognostic impact of TP53 mutations and the survival benefits of treatment intensification strategies (log-rank test Conclusion: Baseline clinical risk, as delineated by the Lung-molGPA, serves as a crucial determinant of therapeutic benefit in cases of EGFR-mutant lung adenocarcinoma with cerebral metastases. Implementing risk-adapted treatment intensification strategies could potentially prevent overtreatment in patients classified as low-risk, while simultaneously optimizing clinical outcomes in high-risk cohorts.
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