RTAD-07 PROTON VERSUS PHOTON VOLUMETRIC MODULATED ARC THERAPY CRANIOSPINAL IRRADIATION FOR HEMATOLOGIC LEPTOMENINGEAL DISEASE: A COMPARATIVE STUDY

Abstract

Craniospinal irradiation (CSI) is an effective treatment for hematologic leptomeningeal disease (LMD). Comparative outcome data for proton CSI (“pCSI”) vs volumetric modulated arc therapy (VMAT, “xCSI”) are not well described in hematologic malignancies, a vulnerable population with often-limited bone marrow reserve. We compared outcomes between xCSI and pCSI, hypothesizing higher toxicity with xCSI but similar survival. Hematologic patients who received CSI between 2013–2025 were identified. Toxicities were graded with CTCAE v.5.0 at baseline, during treatment, and 1- and 3-months post-CSI. Overall survival (OS) from CSI start was analyzed with Cox proportional hazards models adjusted for ECOG. Progression-free survival (PFS) and CNS-PFS were also evaluated. 34 patients received CSI: 26 (76%) xCSI, 8 (24%) pCSI. Dose ranged from 7.2 Gy-30.6 Gy in 4-17 fractions. Baseline characteristics were similar: ALL (59%) and NHL (18%) were most common (p=.51), and most ECOG 1 (p=.80). Non-hematologic toxicities were largely grade 1-2 (fatigue, nausea, pain) with no differences between modalities. Grade ≥3 lymphopenia was more common during xCSI vs pCSI (87.5% vs 50.0%; p=.047) but not at 1 month (36.4% vs 66.7%; p=.35). Median OS was 28.3 months with no difference between xCSI vs pCSI (24.1m vs NR; p=.23), including after ECOG adjustment (HR 0.16; 95% CI 0.02–1.45; p=.10). PFS (8.6m vs 27.9m; p=.30) and CNS-PFS (18.6m vs NR; p=.20) trended higher after pCSI without significant differences. CNS-PFS differed by treatment indication (bridging vs definitive vs consolidation; 18.6m vs 8.6m vs NR, respectively; p=.02). pCSI and xCSI demonstrated comparable toxicity in hematologic patients, supporting the safety of VMAT xCSI. However, higher rates of severe lymphopenia during xCSI warrant attention and may support pCSI in high-risk patients. Outcomes also differed by treatment indication, with poorer CNS control in patients treated definitively. This is an important step toward optimizing neuraxial radiotherapy in hematologic LMD.