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. 2025 Apr 22;20(1):61.
doi: 10.1186/s13014-025-02618-7.

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

Felix Ehret #  1   2   3 , Ammy M Yuan #  4 , Ariel E Marciscano  5 , Stephen Zieminski  6 , Peggy A Leland  6 , Melin J Khandekar  5 , Kevin S Oh  5 , Helen A Shih  5
Affiliations

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

Felix Ehret et al. Radiat Oncol. .

Abstract

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.

Keywords: Brain metastasis; CSI; Craniospinal irradiation; Leptomeningeal disease; Leptomeningeal metastasis; Proton therapy.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the local institutional review board (protocol number 2024P000907). Consent for publication: Not applicable. Competing interests: Felix Ehret gratefully acknowledges funding from the German Cancer Aid (Mildred-Scheel Postdoctoral Fellowship) and Accuray, Inc., and received honoraria and travel support from ZAP Surgical Systems, Inc.

Figures

Fig. 1
Fig. 1
Time to (A) CNS progression, (B) CNS progression-free survival
Fig. 2
Fig. 2
Progression-free survival for (A) Full cohort, (B) Stratified for concurrent targeted therapy, (C) Stratified for the extent of LMD, (D) Stratified for the median Karnofsky performance status
Fig. 3
Fig. 3
Overall survival for (A) Full cohort, (B) Stratified for concurrent targeted therapy, (C) Stratified for the extent of LMD, (D) Stratified for the median Karnofsky performance status
Fig. 4
Fig. 4
Case example. (A, B) 58-year-old male, KPS of 90%, with the diagnosis of extensive-stage small cell lung cancer and widespread cerebellar leptomeningeal disease on contrast-enhanced magnetic resonance imaging (MRI). He received chemotherapy with carboplatin and etoposide as well as immunotherapy with atezolizumab before and after proton craniospinal irradiation (pCSI) (C) pCSI treatment plan, 30 Gy (RBE) total dose, 10 fractions. (D, E) Three months after pCSI, contrast-enhanced MRI demonstrated complete resolution of LMD
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References

    1. Wang N, Bertalan MS, Brastianos PK. Leptomeningeal metastasis from systemic cancer: review and update on management. Cancer. 2018;124(1):21–35. - PMC - PubMed
    1. Buszek SM, Chung C. Radiotherapy in leptomeningeal disease: a systematic review of randomized and non-randomized trials. Front Oncol. 2019;9:1224. - PMC - PubMed
    1. Wilcox JA et al. Leptomeningeal metastases from solid tumors: a SNO and ASCO consensus review on clinical management and future directions. Neuro Oncol. 2024 Oct 3;26(10):1781–804. - PMC - PubMed
    1. Clarke JL, et al. Leptomeningeal metastases in the MRI era. Neurology. 2010;74(18):1449–54. - PMC - PubMed
    1. El Shafie RA, et al. Palliative radiotherapy for leptomeningeal carcinomatosis-analysis of outcome, prognostic factors, and symptom response. Front Oncol. 2018;8:641. - PMC - PubMed

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