Early experience with proton craniospinal irradiation in adult patients with leptomeningeal disease

Background: Leptomeningeal disease (LMD) is a fatal complication of cancer linked to poor survival rates and limited treatment options. While photon involved-field radiotherapy is the standard of care for local palliation and symptom alleviation, it lacks durable disease control. Recent data suggest proton craniospinal irradiation (pCSI) to be a promising treatment option, potentially prolonging progression-free survival (PFS) and overall survival (OS). Herein, we report our initial experience with pCSI for treating LMD from solid malignancies. Methods: Adult patients treated with pCSI for LMD were identified, with analysis of patient, tumor, and treatment characteristics as well as clinical outcomes. Results: Nine patients were eligible for analysis who were treated between February 2023 and February 2024. The median age at pCSI and Karnofsky performance status (KPS) were 58.6 years and 80%, respectively. The primary disease was breast cancer in 33.3%, and LMD involved both the brain and spine in 55.5%. Approximately half of the patients (55.5%) had a cerebrospinal fluid diversion before treatment, and nearly all patients underwent pCSI with 30 Gy (relative biological effectiveness) in 10 fractions. All patients completed pCSI as planned. The median clinical and central nervous system (CNS) radiographic follow-up periods were both 3.5 months. Six deaths were observed during the available follow-up. The median PFS, CNS PFS, and OS were 2.7, 4.0, and 4.0 months, respectively. Younger age, higher KPS, and concurrent treatment with targeted therapy were associated with longer OS, while cases with LMD involving both the brain and spine had shorter survival. The observed toxicity was manageable, without any occurrence of grade 4 or 5 toxicity. Conclusion: pCSI can be an effective and safe treatment option for a highly selected population of patients with LMD. Further data and prospective studies are warranted to clarify its role in the management of LMD.