Impact of EGFR mutation subtypes and TKI generations on clinical outcomes in lung adenocarcinoma patients with brain metastases treated with gamma knife radiosurgery.

BACKGROUND

Brain metastases are a common and severe complication in patients with lung adenocarcinoma (ADC) harboring epidermal growth factor receptor (EGFR) mutations. Gamma Knife Radiosurgery (GKRS) is a standard treatment for brain metastases, and its efficacy may be influenced by the type of EGFR mutation and the generation of tyrosine kinase inhibitors (TKIs) used. This retrospective study evaluated the impact of EGFR mutation subtypes (exon 19 deletion vs. exon 21 L858R) and TKI generations on clinical outcomes in patients with lung ADC treated with GKRS.

METHODS

A total of 55 patients and 136 brain metastases were analyzed from January 2017 to December 2023. Tumor response was assessed based on local failure and distant brain failure, defined as tumor progression at the treated site and new brain metastases outside the GKRS-treated regions, respectively. The Kaplan-Meier method and univariate and multivariate analyses using Cox proportional hazard regression models were used to identify prognostic factors for local failure, and distant brain failure.

RESULTS

The study found that second- and third-generation TKIs, such as afatinib and osimertinib, provided significantly better local control compared to first-generation TKIs (hazard ratio [HR] = 0.12, p = 0.017). Furthermore, tumors with exon 19 deletion demonstrated improved distant brain control compared to those with exon 21 L858R substitution (HR = 2.18, p = 0.048). These findings suggest that mutation type and TKI generation are independent prognostic factors for clinical outcomes following GKRS.

CONCLUSION

This study suggests that both the generation of TKIs and the specific EGFR mutation subtype may influence clinical outcomes following GKRS in lung ADC patients with brain metastases. These findings may aid in stratifying patients and optimizing treatment strategies in clinical practice.