{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:32:57Z","timestamp":1791502377897,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The optimal treatment for vitreoretinal lymphoma (VRL) remains a challenge, as central nervous system (CNS) relapse occurs frequently, leading to the worst impact on survival. We previously proposed combined intravitreal methotrexate and systemic high\u2010dose methotrexate therapy for this disease. This study aimed to report the long\u2010term outcomes of patients with VRL using this combination treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study on patients with VRL at a tertiary referral center between 2003 and 2018.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty\u2010two patients were included, of whom 23 had primary VRL (PVRL) and nine had concurrent intraocular and CNS diseases. The treatment was well tolerated. Twenty\u2010six (81.3%) patients achieved complete response (CR). After a median follow\u2010up time of 103.5\u2009months, the 5\u2010year survival rate was 73.3%, whereas the 5\u2010year progression\u2010free survival (PFS) rate was 29.9%. Twenty\u2010four (75%) patients relapsed, including 12 with isolated intraocular relapses at first relapse and a total of 17 with CNS\/systemic relapses. The development of CNS\/systemic relapse negatively affected survival, but intraocular relapse did not. The median CNS\/systemic PFS was 69.5\u2009months, but the risk of CNS\/systemic relapse increased steadily with a cumulative incidence rate at 2, 5, and 10\u2009years being 22.6%, 44.2%, and 65%, respectively. Multivariate analysis identified concurrent CNS disease at diagnosis as the only poor\u2010risk factor for CNS\/systemic relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study confirms good efficacy and acceptable toxicities of the combination approach. However, incorporation of further intensive consolidation strategies into the treatment protocol to effectively prevent subsequent CNS\/systemic relapse deserves to be considered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.5609","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T08:36:25Z","timestamp":1672907785000},"page":"8102-8111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Long\u2010term outcomes of combined intravitreal methotrexate and systemic high\u2010dose methotrexate therapy in vitreoretinal lymphoma"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5442-1079","authenticated-orcid":false,"given":"Chieh\u2010Lung","family":"Cheng","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine National Taiwan 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