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. 2023 Sep;164(2):387-396.
doi: 10.1007/s11060-023-04442-z. Epub 2023 Sep 10.

EGFR-mutated non-small lung cancer brain metastases and radiosurgery outcomes with a focus on leptomeningeal disease

Juan Diego Alzate  1 , Reed Mullen  2 , Elad Mashiach  2 , Kenneth Bernstein  3 , Fernando De Nigris Vasconcellos  2 , Lauren Rotmann  2 , Assaf Berger  2 , Tanxia Qu  3 , Joshua S Silverman  3 , John G Golfinos  2 , Bernadine R Donahue  3 , Douglas Kondziolka  2
Affiliations

EGFR-mutated non-small lung cancer brain metastases and radiosurgery outcomes with a focus on leptomeningeal disease

Juan Diego Alzate et al. J Neurooncol. 2023 Sep.

Abstract

Purpose: Patients with EGFR-mutated NSCLC represent a unique subset of lung cancer patients with distinct clinical and molecular characteristics. Previous studies have shown a higher incidence of brain metastases (BM) in this subgroup of patients, and neurologic death has been reported to be as high as 40% and correlates with leptomeningeal disease (LMD).

Methods: Between 2012 and 2021, a retrospective review of our prospective registry identified 606 patients with BM from NSCLC, with 170 patients having an EGFR mutation. Demographic, clinical, radiographic, and treatment characteristics were correlated to the incidence of LMD and survival.

Results: LMD was identified in 22.3% of patients (n = 38) at a median follow-up of 19 (2-98) months from initial SRS. Multivariate regression analysis showed targeted therapy and a cumulative number of metastases as significant predictors of LMD (p = 0.034, HR = 0.44), (p = .04, HR = 1.02). The median survival time after SRS of the 170 patients was 24 months (CI 95% 19.1-28.1). In a multivariate Cox regression analysis, RPA, exon 19 deletion, and osimertinib treatment were significant predictors of overall survival. The cumulative incidence of neurological death at 2 and 4 years post initial stereotactic radiosurgery (SRS) was 8% and 11%, respectively, and correlated with LMD.

Conclusion: The study shows that current-generation targeted therapy for EGFR-mutated NSCLC patients may prevent the development and progression of LMD, leading to improved survival outcomes. Nevertheless, LMD is associated with poor outcomes and neurologic death, making innovative strategies to treat LMD essential.

Keywords: Epidermal growth factor receptor; Leptomeningeal disease; Non-small cell lung cancer; Tyrosine kinase inhibitor.

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