Journal
NEURO-ONCOLOGY
Volume 23, Issue 1, Pages 134-143Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/noaa152
Keywords
craniospinal irradiation; leptomeningeal metastases; proton radiation
Categories
Funding
- Cycle for Survival Equinox Innovation Initiative Award
- National Institutes of Health/National Cancer Institute [P30-CA008748]
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Proton craniospinal irradiation is a safe treatment for patients with leptomeningeal metastases from solid tumors, with durable disease control observed in some patients.
Background. Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. Methods. We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial. The primary endpoint was to describe treatment-related toxicity, with dose-limiting toxicity (DLT) defined as any radiation-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity according to the Common Terminology Criteria for Adverse Events that occurred during or within 4 weeks of completion of proton CSI. Secondary endpoints included CNS progression-free survival (PFS) and overall survival (OS). Results. We enrolled 24 patients between June 2018 and April 2019. Their median follow-up was 11 months. Twenty patients were evaluable for protocol treatment-related toxicities and 21 for CNS PFS and OS. Two patients in the dose expansion cohort experienced DLTs consisted of grade 4 lymphopenia, grade 4 thrombocytopenia, and/or grade 3 fatigue. All DLTs resolved without medical intervention.The median CNS PFS was 7 months (95% CI: 5-13) and the median OS was 8 months (95% CI: 6 to not reached). Four patients (19%) were progression-free in the CNS for more than 12 months. Conclusion. Hypofractionated proton CSI using proton therapy is a safe treatment for patients with LM from solid tumors. We saw durable disease control in some patients.
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