Synapse - Proton craniospinal irradiation for patients with leptomeningeal metastasis

Proton craniospinal irradiation for patients with leptomeningeal metastasis Journal Article

Authors:	Yang, J. T.; Yerramilli, D.; Pentsova, E.; Wolden, S.; Young, R. J.; Correa, D. D.; Imber, B. S.; Wijetunga, N. A.; Goglia, A. G.; Zhang, Z.; Zheng, J.; Baser, R.; Bernstein, A.; Kratochvil, L.; Xiao, J.; Hattangadi-Gluth, J.; Miller, A. M.; Wilcox, J. A.; Warner, A. B.; Yu, H.; Kris, M. G.; Seidman, A. D.; Powell, S. N.; Boire, A.
Article Title:	Proton craniospinal irradiation for patients with leptomeningeal metastasis
Abstract:	<p>ImportanceLeptomeningeal metastasis (LM) is associated with limited survival and few treatment options. Photon involved-field radiotherapy (IFRT) is the most common radiotherapy treatment for patients with LM from solid tumors. ObjectiveTo assess whether proton craniospinal irradiation (pCSI) would result in superior central nervous system progression-free survival (CNS-PFS) compared with IFRT. Design, Setting, and ParticipantsA randomized, phase 2 trial of pCSI vs IFRT was conducted between April 16, 2020, and October 11, 2021, and included patients with non-small cell lung cancer and breast cancer with LM. Patients with other solid tumors were also enrolled in an exploratory pCSI cohort. InterventionFor the randomized groups, after stratifying by histology and systemic disease status, patients were assigned (2:1) to pCSI or IFRT. Main Outcomes and MeasuresThe primary end point was CNS-PFS. Secondary end points included overall survival (OS). ResultsOf 98 total patients, 72 individuals (73.5%) were female, and the median (IQR) age was 59 (50-65) years. A total of 42 and 21 patients were randomly assigned to pCSI and IFRT, respectively. At planned interim analysis, a significant benefit in CNS-PFS was observed with pCSI compared with IFRT, leading to the early discontinuation of the trial. In this final analysis, a significant benefit was continually observed in CNS-PFS with pCSI (median, 8.2 months; 95% CI, 6.6-15.3) vs IFRT (median, 2.3 months; 95% CI, 1.2-4.0; P < .001). A statistically significant and clinically meaningful OS benefit with pCSI (median, 11.3 months; 95% CI, 7.5-18.3) vs IFRT (median, 4.9 months; 95% CI, 3.9-15.0; P = .04) was also observed. For the exploratory pCSI cohort (n = 35), the median CNS-PFS was 5.8 months (95% CI, 4.4-9.1) and OS was 7.0 months (95% CI, 5.4-10.6). Conclusions and RelevanceThis randomized clinical trial that assessed the optimal radiotherapy treatment for LM found improved CNS-PFS and OS with pCSI compared with IFRT. The results suggest that pCSI should be considered when available. Trial RegistrationClinicalTrials.gov Identifier: NCT04343573</p>
Keywords:	toxicity; dysfunction; whole-brain radiotherapy; cancer
Journal Title:	JAMA Oncology
ISSN:	2374-2437
Publisher:	American Medical Association
Publication status:	Online ahead of print
Date Published:	2025-09-04
Online Publication Date:	2025-09-04
Language:	English
ACCESSION:	WOS:001566844000001
DOI:	10.1001/jamaoncol.2025.3007
PROVIDER:	wos
PMCID:	PMC12412039
PUBMED:	40906462
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Wos