{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:14:18Z","timestamp":1788970458762,"version":"build-2803163510"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Cancer Center Research and Development Fund","award":["2023-J-03"],"award-info":[{"award-number":["2023-J-03"]}]},{"name":"National Cancer Center Research and Development Fund","award":["2026-J-03"],"award-info":[{"award-number":["2026-J-03"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25ck0106079"],"award-info":[{"award-number":["JP25ck0106079"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy. Patients refractory to high-dose methotrexate\u2013based induction therapy have an extremely poor prognosis. Although whole-brain radiotherapy (WBRT) is the standard salvage treatment and provides potent tumor control, early functional deterioration and late neurocognitive toxicity remain major concerns. A phase I\/II trial on relapsed or refractory PCNSL demonstrated favorable efficacy and tolerability of tirabrutinib, a second-generation selective Bruton\u2019s tyrosine kinase inhibitor. Tirabrutinib\u2019s oral administration has enabled outpatient management. However, its clinical value for induction-refractory PCNSL remains uncertain. We designed a multicenter, randomized phase II\/III trial (JCOG2314) to assess the non-inferiority of tirabrutinib to WBRT in overall survival and its potential to reduce functional deterioration and cognitive impairment. A total of 94 patients from 49 institutions will be enrolled over 4 years. The trial has been registered in the Japan Registry of Clinical Trials (study number: jRCT1031250645).<\/jats:p>","DOI":"10.1093\/jjco\/hyag090","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:20:25Z","timestamp":1781612425000},"page":"1145-1151","source":"Crossref","is-referenced-by-count":0,"title":["A multicenter randomized phase II\/III trial of salvage treatment for refractory primary central nervous system lymphoma using tirabrutinib: JCOG2314 (ReSTART)"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5057-7985","authenticated-orcid":false,"given":"Kota","family":"Kawabata","sequence":"first","affiliation":[{"name":"Japan Clinical Oncology Group Data Center\/Operations Office, National Cancer Center Hospital , 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-5626","authenticated-orcid":false,"given":"Fumiharu","family":"Ohka","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Medicine, Nagoya University , 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2484-1360","authenticated-orcid":false,"given":"Ryuta","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Graduate School of Medicine, Nagoya University , 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Onoe","sequence":"additional","affiliation":[{"name":"Radiation and Proton Therapy Center, Shizuoka Cancer Center , 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6450-3027","authenticated-orcid":false,"given":"Hideyuki","family":"Harada","sequence":"additional","affiliation":[{"name":"Radiation and Proton Therapy Center, Shizuoka Cancer Center , 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5593-9045","authenticated-orcid":false,"given":"Takashi","family":"Sasayama","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Kobe University Graduate School of Medicine , 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Yokoo","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma 371-8511,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4626-4645","authenticated-orcid":false,"given":"Yoshiki","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Kyoto University Graduate School of Medicine , 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-5298","authenticated-orcid":false,"given":"Junki","family":"Mizusawa","sequence":"additional","affiliation":[{"name":"Japan Clinical Oncology Group Data Center\/Operations Office, National Cancer Center Hospital , 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0082-9028","authenticated-orcid":false,"given":"Noriko","family":"Mitome","sequence":"additional","affiliation":[{"name":"Japan Clinical Oncology Group Data Center\/Operations Office, National Cancer Center Hospital , 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5100-3863","authenticated-orcid":false,"given":"Keita","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Japan Clinical Oncology Group Data Center\/Operations Office, National Cancer Center Hospital , 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Japan Clinical Oncology Group Data Center\/Operations Office, National Cancer Center 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