Abstract
Craniospinal irradiation (CSI) is an effective treatment for solid tumor leptomeningeal carcinomatosis (LMC). While proton CSI (pCSI) has demonstrated improved survival compared to involved-field photon therapy, outcomes using volumetric modulated arc therapy (VMAT, or “xCSI”) for full neuraxis coverage remain unclear. This study compared toxicity and outcomes among patients with solid tumor LMC treated with either pCSI or xCSI, with the hypothesis that xCSI would be associated with increased toxicity but similar survival when adjusted for performance status. Adults diagnosed with LMC and treated with CSI to 30 Gy in 10 fractions between 2020 and 2025 were included. Acute and late toxicities (hematologic, fatigue, nausea, headache) were graded using CTCAE v5.0 during treatment and at 1- and 3-months post-CSI. Overall survival (OS) was calculated from CSI start and analyzed using Cox proportional hazards models adjusted for ECOG performance status and metastatic burden, defined as low (<2 organs) vs high (≥3 organs) involvement. Of 37 patients (median age 54), 21 (57%) received pCSI and 16 (43%) xCSI. Most patients had ECOG 1 (p=0.262), with breast (41%) and lung (38%) as the most common histologies (p=0.323). Grade ≥1 thrombocytopenia was significantly higher during xCSI (1.54 vs 0.36, p=0.005) but resolved by 1 month. No other significant differences in hematologic or non-hematologic toxicities were observed. Median OS was not significantly different: 11.6 months for pCSI vs 4.6 months for xCSI (p=0.238) and remained nonsignificant after adjusting for ECOG (HR 1.3; 95% CI, 0.17–1.34) and metastatic burden (HR 0.52; 95% CI, 0.19–1.47). However, low-volume metastatic disease was significantly associated with improved OS (HR 0.35; 95% CI, 0.14–0.91; p=0.032), independent of treatment modality. These findings support the safety of VMAT xCSI and suggest observed survival differences may reflect patient selection. Further study is needed to define xCSI’s role in LMC management.