Early Outcomes from Proton Craniospinal Irradiation for Leptomeningeal Metastasis from Solid Tumors

Abstract

IntroductionTreatment options for leptomeningeal metastasis (LM) are limited. A recent phase II study found that proton craniospinal irradiation (pCSI) was well-tolerated and improved survival. We report our experience with pCSI for solid-tumor LM. MethodsThis is a retrospective review of patients treated with pCSI for solid-tumor LM from December 2020 to January 2024 at our center. Patient characteristics were summarized using descriptive statistics. Median overall survival and median central nervous system progression-free survival from the first day of pCSI were estimated using Kaplan-Meier survival curves. ResultsWe identified 45 patients who completed pCSI. Median age was 54 years (range, 23-79); 73% were female, and 53% lived more than 100 miles from our center. Breast cancer (53%), lung cancer (20%), and melanoma (9%) were the most common primary cancers; 51% of patients had stable systemic disease at LM diagnosis. All had imaging evidence of LM, and 64% of cases were confirmed by cytologic examination of the cerebrospinal fluid. Eighty percent had symptomatic LM, and the median Karnofsky Performance Scale (KPS) at LM diagnosis was 80. The median time from primary cancer diagnosis to LM detection was 23.1 months (range, 0-221.3). Fifty-three percent of patients had active brain metastasis at LM diagnosis; 33% of all patients had received prior intracranial radiation. Median time from simulation to pCSI start was 12 days. At the first visit following pCSI, median KPS was 70. During or right after radiation, seventy-six percent of patients reported nausea, 51% headache, and 31% fatigue. Following pCSI, 4% received intrathecal chemotherapy, 67% systemic therapy, and 9% hospice care; 18% were observed and 2% lost to follow up. Median overall survival was 13.7 months (95% confidence interval [CI], 11.2 to not reached), and median progression-free survival was 6.5 months (95% CI, 4.9 to 12.8). ConclusionsThe outcomes in our cohort are comparable to those recently reported in a phase II trial. Further study is indicated to determine the optimal candidates for pCSI and sequential therapies.