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However, its features in patients with sCNSi who are categorized as lower risk by international prognostic index (IPI) or CNS-IPI are not yet fully understood. In the present analysis, we evaluated DLBCL patients who developed sCNSi at their first progression and who participated in JCOG0601, most of whom were lower risk by IPI. Of 409 patients, 21 (5.1%) developed sCNSi during a median follow-up of 4.9\u00a0years. Five-year cumulative incidence of sCNSi were 5.1%; and 4.0%, 5.3%, and 11.5% at low, intermediate, and high risk of CNS-IPI, respectively. The most common locations of extranodal lesions at the time of registration in patients with sCNSi were the stomach (n\u2009=\u20094), paranasal cavity (n\u2009=\u20093), and bone marrow (n\u2009=\u20092). In univariable analysis, paranasal cavity lesion was a high-risk factor for sCNSi (subdistribution hazard ratio, 4.34 [95% confidence interval 1.28\u201314.73]). Median overall survival after sCNSi was 1.3\u00a0years, with a 2-year overall survival rate of 39.3%. The incidence of sCNSi in DLBCL patients at lower risk of CNS-IPI was low, as previously reported, but paranasal cavity lesion might indicate high risk for organ involvement.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Clinical trial registration<\/jats:title>\n                <jats:p>JCOG0601 was registered in the UMIN Clinical Trials Registry (UMIN000000929, date of registration; December 04, 2007) and the Japan Registry of Clinical Trials (jRCTs031180139, date of registration; February 20, 2019).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00277-024-05620-3","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T05:01:56Z","timestamp":1706331716000},"page":"2021-2031","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Secondary central nervous system involvement in patients with diffuse large B-cell lymphoma treated with rituximab combined CHOP therapy \u2013 a supplementary analysis of JCOG0601"],"prefix":"10.1007","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1075-9219","authenticated-orcid":false,"given":"Kazuyuki","family":"Shimada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Ohmachi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryunosuke","family":"Machida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuichi","family":"Ota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidekazu","family":"Itamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Tsujimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Takayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaki","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsutoshi","family":"Kurosawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Tabayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsu","family":"Shimoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Ohshima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kana","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dai","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Ando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomitsu","family":"Hotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Tsukasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"5620_CR1","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1093\/annonc\/mdp432","volume":"21","author":"D Villa","year":"2010","unstructured":"Villa D, Connors JM, Shenkier TN et al (2010) Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. 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The study protocol was approved by the Protocol Review Committee of Japan Clinical Oncology Group (JCOG) and the institutional review board of each participating center and the central review board of National Cancer Center (Tokyo, Japan), since enforcement of the Clinical Trials Act in Japan.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all patients before enrollment of the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"KS reported receiving grants and personal fees from Celgene, and Kyowa Kirin, grants from Otsuka, and personal fees from AstraZeneca, Eisai, Takeda, Janssen, Bristol Myers Squibb, Chugai, Nippon Shinyaku, Daiichi Sankyo, Meiji Seika, Ono, AbbVie, Novartis, Gilead, CSL Behling, Incyte, and Genmab outside the submitted work. KO reported receiving personal fees from Chugai, Kyowa Kirin, Meiji Seika, and Pfizer outside the submitted work. SO reported receiving personal fees from Novartis, Bristol Myers Squibb, Takeda, AstraZeneca, Janssen, and AbbVie outside the submitted work. NT reported receiving personal fees from Chugai and Kyowa Kirin outside the submitted work. TS reported receiving personal fees from Chugai, Novartis, Bristol Myers Squibb, Kyowa Kirin, and Taiho outside the submitted work. KM reported receiving grants and personal fees from Eisai, Nippon Shinyaku, Chugai, Asahi Kasei, and Sumitomo Dainippon, grants from Takeda, Otsuka, and Zenyaku, and personal fees from SymBio, Janssen, AstraZeneca, Bristol Myers Squibb, Meiji Seika, AbbVie, Novartis, and Incyte outside the submitted work. DM reported receiving grants and personal fees from AbbVie, Celgene, Kyowa Kirin, Chugai, Ono, Takeda, Janssen, Sanofi, Bristol Myers Squibb, Eisai, and MSD, grants from Amgen Astellas Biopharma, Novartis, Otsuka, Astellas, and Taiho, and personal fees from Nippon Shinyaku, Mundipharma, Zenyaku, SymBio, and AstraZeneca outside the submitted work. KA reported receiving grants from Chugai, Nippon Shinyaku, Takeda, Eisai, and Kyowa Kirin, and personal fees from Celgene, Otsuka, Novartis, and Astellas outside the submitted work. KT reported receiving grants from National Cancer Center and the Ministry of Health, Labour and Welfare during the conduct of the study, grants and personal fees from Meiji Seika, Daiichi Sankyo, and HUYABIO, grants from Kyowa Kirin, Bristol Myers Squibb, Bayer, and Regeneron, and personal fees from Ono, Solasia, Yakuruto, Eisai, and Takeda outside the submitted work. HN reported receiving grants and personal fees from AstraZeneca, Celgene, Mundipharma, Takeda, Chugai, Bristol Myers Squibb, Jansen, Kyowa Kirin, SymBio, Ono, and Eisai, grants from Zenyaku Kogyo, Bayer, AbbVie, MSD, and Nippon Shinyaku, and personal fees from Sanofi, Novartis, Chordia Therapeutics, Nihon Medi-Physics, and Meiji Seika outside the submitted work. All other authors have nothing to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}