Early Outcomes from Proton Craniospinal Irradiation (pCSI) for Leptomeningeal Disease from Solid Tumors

Abstract

Prospective data suggest that proton craniospinal irradiation (pCSI) improves overall survival (OS) in patients with leptomeningeal disease (LMD) from solid tumors, compared to the historical standard of involved field radiation. To evaluate outcomes of this novel approach in a real-world setting, our institutional experience with treating adults with pCSI for LMD from solid malignancies was evaluated. On an IRB-approved protocol, medical records of adults with LMD from solid tumors treated with pCSI were retrospectively reviewed for patient, disease and treatment characteristics and outcomes. CNS-PFS and OS were calculated from the last day of pCSI, and survival was modeled using Kaplan-Meier analysis. From December 2021 to November 2022, 17 patients with median age 51y (range 22-71y) were treated with pCSI for LMD from solid tumors. Thirteen patients (76%) were female. Ten had ECOG PS of 0-1, and seven had PS 2-3. Nine patients (53%) had breast cancer, 3 (18%) had non-small cell lung cancer (NSCLC), 2 (12%) had melanoma, 1 (6%) had colorectal adenocarcinoma, 1 (6%) had endocervical adenocarcinoma, and 1 (6%) had two synchronous primaries (adenocarcinoma of the gastro-esophageal junction and neuroendocrine carcinoma of the lung). All patients had prior radiation; ten had prior radiation to the brain, one had prior radiation to the spine, and six had other sites previously radiated. Fourteen patients (82%) were treated to 30 Gy in 10 fractions and 3 (18%) were treated to 25 Gy in 10 fractions due to overlap with prior radiation fields. Median follow-up was 4 months (range, 1-13 months). Among 15 evaluable patients, median CNS-PFS and median OS were 3.6 months and 4.7 months, respectively. For patients with breast cancer or NSCLC, 62% were alive at 6 months; median OS has not been reached. Treatment was well tolerated with no grade 3-4 non-hematologic adverse events. pCSI is a novel method for treatment of LMD from solid tumors that has been rapidly adopted. Based on our preliminary review, it is safe and well-tolerated; patient selection is critical. As these patients are often heavily pretreated, prior radiation fields must be considered in pCSI planning.