{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T14:59:19Z","timestamp":1794668359442,"version":"4.9.1"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Leptomeningeal 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess whether proton craniospinal irradiation (pCSI) would result in superior central nervous system progression-free survival (CNS-PFS) compared with IFRT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>A randomized, phase 2 trial of pCSI vs IFRT was conducted between April 16, 2020, and October 11, 2021, and included patients with non\u2013small cell lung cancer and breast cancer with LM. Patients with other solid tumors were also enrolled in an exploratory pCSI cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>For the randomized groups, after stratifying by histology and systemic disease status, patients were assigned (2:1) to pCSI or IFRT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary end point was CNS-PFS. Secondary end points included overall survival (OS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 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;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). 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;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.04) was also observed. For the exploratory pCSI cohort (n\u2009=\u200935), 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).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>This 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04343573?term=NCT04343573&amp;amp;amp;rank=1\">NCT04343573<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoncol.2025.3007","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T15:31:09Z","timestamp":1756999869000},"page":"1293","source":"Crossref","is-referenced-by-count":27,"title":["Proton Craniospinal Irradiation for Patients With Leptomeningeal Metastasis"],"prefix":"10.1001","volume":"11","author":[{"given":"Jonathan T.","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York"},{"name":"Department of Radiation Oncology, New York University Grossman School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Yerramilli","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pentsova","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Wolden","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise D.","family":"Correa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon S.","family":"Imber","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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