Prognosis after Whole-Brain Radiotherapy for Leptomeningeal Metastasis in Patients with Lung Adenocarcinoma with or without EGFR/ALK Alterations

Abstract

<h3>Purpose/Objective(s)</h3> Whole-brain radiotherapy (WBRT) is a treatment option for patients with leptomeningeal metastasis (LM) from lung adenocarcinoma. However, there is no consensus on the indication of WBRT, mainly due to a lack of selection criteria for patients who will benefit from WBRT. In addition, the factors associated with better clinical outcomes after WBRT have not been well elucidated. In particular, the impact of <i>EGFR</i> mutations or <i>ALK</i> rearrangement on survival in patients receiving WBRT for LM remains unclear. Here, we conducted a retrospective study to evaluate the prognosis of patients receiving WBRT for LM. <h3>Materials/Methods</h3> We retrospectively evaluated a total of 72 patients who received WBRT for LM from lung adenocarcinoma at our institution between June 2013 and August 2020. Seventy-one patients (98.6%) were diagnosed as LM by radiographic findings without cerebrospinal fluid cytology. Overall survival (OS) was calculated in all 72 patients from the starting date of WBRT until death. The following variables were analyzed as the factors associated with OS: Eastern Cooperative Oncology Group performance status (PS), age, <i>EGFR/ALK</i> status, the number of brain metastases, presence of extracranial metastasis, and primary tumor control. <h3>Results</h3> Among the 72 patients examined, <i>EGFR</i> mutations were found in 40, <i>ALK</i> rearrangement was found in 6, co-alterations were found in 1, and 25 patients had a wild-type for <i>EGFR</i> and <i>ALK</i> alterations. The median follow-up time was 5.2 months (range, 0.5–49.3), 54 of 72 patients (75.0%) died of disease progression, and the median OS was 6.2 months (95% CI; 4.4–12.5). Multivariate analysis indicated that PS 0–1 (<i>P</i> < 0.001), controlled primary tumor (<i>P</i> = 0.011) were independent positive predictors of OS after WBRT. <i>EGFR</i> mutation or <i>ALK</i> rearrangement was not an independent predictor of OS after WBRT (<i>P</i> = 0.10). Of the 47 patients with <i>EGFR</i>-mutant or <i>ALK</i>-rearranged lung adenocarcinoma, 10 received central nervous system–penetrant TKIs against LM before WBRT (the median time from LM diagnosis to WBRT was 2.7 months [range, 1.4–37.2]). No significant survival difference was observed between those with and without prior TKI use (median OS 8.1 vs. 12.5 months, respectively). <h3>Conclusion</h3> Good PS and controlled primary tumor had a significant positive impact on OS after WBRT for LM. <i>EGFR</i> or <i>ALK</i> status did not influence OS.