Analysis reveals distinct toxicity profiles and survival rates for proton and photon craniospinal irradiation in leptomeningeal carcinomatosis.
Craniospinal irradiation (CSI) is an effective treatment for solid tumor leptomeningeal carcinomatosis (LMC). Although proton CSI (pCSI) improves survival vs involved-field photon therapy, differences in outcomes when treating the entire neuraxis with volumetric modulated arc therapy (VMAT, or “xCSI”) remain unclear. We compared toxicity and outcomes for solid tumor LMC treated with pCSI vs xCSI, hypothesizing greater hematologic toxicity with xCSI but similar performance status-adjusted survival. Adults diagnosed with LMC and planned for CSI to 30Gy/10fx from 2020–2025 were included. Acute and late (1, 3m post-CSI) hematologic toxicities were graded per CTCAE v5.0. Systemic and intrathecal (IT) therapy pre- and post-CSI were recorded. CNS progression-free (PFS) and overall (OS) survivals were calculated from CSI start with Cox proportional hazards models adjusting for ECOG status. Of 36 patients, 33 completed CSI: 20 (61%) pCSI, 13 (39%) xCSI. Median age was 53yo, most were ECOG 0-1 (p=0.4), and most histologies were breast (42%) or lung (36%; p=0.3). After CSI, systemic therapy use was higher in pCSI (92% vs 46%, p=0.03), while IT use was similar. Acute anemia (G1+) was more common with xCSI (61% vs 20%, p=0.04), trending towards higher acute lymphopenia (88% vs 67% G3+, p=0.09). At 1m, leukopenia (G1+) trended higher with xCSI (46% vs 10%, p=0.05). At 3m, toxicity differences resolved. Median OS was 10.7m (95% CI 4.6-NR: 10.9m pCSI, 4.6m xCSI; p=0.03). Median CNS PFS was 5.5m (95% CI 1-NR: 8.5m pCSI, 3.0 xCSI; p=0.02). There was no significant difference in ECOG-adjusted OS (HRxCSI 1.3 [95% CI 0.9-14.9]; p=0.07) or CNS PFS (HRxCSI 1.4 [95% CI 1.0-15.4]; p=0.05). This is the first comparison of pCSI vs xCSI for solid tumor LMC, suggesting VMAT xCSI safety and that survival differences reflect patient selection. Given its wider availability, further work is needed to clarify VMAT’s role in LMC management.
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Lamanilao et al. (2025) studied this question.
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