{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:01:42Z","timestamp":1792803702812,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Horizon Europe STEPUPIORS Project","award":["HORIZON-WIDERA-2021-ACCESS-03"],"award-info":[{"award-number":["HORIZON-WIDERA-2021-ACCESS-03"]}]},{"name":"Horizon Europe STEPUPIORS Project","award":["101079217"],"award-info":[{"award-number":["101079217"]}]},{"name":"Horizon Europe STEPUPIORS Project","award":["451-03-136\/2025-03\/200043"],"award-info":[{"award-number":["451-03-136\/2025-03\/200043"]}]},{"name":"European Commission","award":["HORIZON-WIDERA-2021-ACCESS-03"],"award-info":[{"award-number":["HORIZON-WIDERA-2021-ACCESS-03"]}],"id":[{"id":"https:\/\/ror.org\/00k4n6c32","id-type":"ROR","asserted-by":"crossref"}]},{"name":"European Commission","award":["101079217"],"award-info":[{"award-number":["101079217"]}],"id":[{"id":"https:\/\/ror.org\/00k4n6c32","id-type":"ROR","asserted-by":"crossref"}]},{"name":"European Commission","award":["451-03-136\/2025-03\/200043"],"award-info":[{"award-number":["451-03-136\/2025-03\/200043"]}],"id":[{"id":"https:\/\/ror.org\/00k4n6c32","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["HORIZON-WIDERA-2021-ACCESS-03"],"award-info":[{"award-number":["HORIZON-WIDERA-2021-ACCESS-03"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["101079217"],"award-info":[{"award-number":["101079217"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200043"],"award-info":[{"award-number":["451-03-136\/2025-03\/200043"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Ultra-low-dose radiotherapy (ULD-RT), an ultra-low-dose regimen delivering 4 Gy in two fractions, has emerged as a promising treatment for indolent ocular adnexal lymphoma (OAL), offering disease control with minimal toxicity. However, the clinical outcomes and safety profile of ULD-RT remain inconsistently reported across studies. Methods: We conducted a systematic review of peer-reviewed studies evaluating ULD-RT in patients with OAL, including prospective, retrospective, and comparative cohorts published between 2000 and 2025. A comprehensive search was performed in PubMed, Embase, and Scopus. Eligible studies reported clinical outcomes (e.g., response rates, local control, progression-free survival) and safety data (acute and late toxicities). Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Results: Ten studies comprising 591 patients met the inclusion criteria. The overall response rate to ULD-RT ranged from 88% to 100%, with complete response rates of 50% to 95%. Local control rates ranged from 63% to 100%, and 2-year progression-free survival exceeded 85% in most studies. Importantly, no grade \u2265 3 toxicities were observed following the regimen of 4 Gy in two fractions. Acute toxicities occurred in up to 42% of patients, typically grade 1 dry eye or conjunctivitis. Late toxicities were uncommon (16\u201333%), with cataracts rarely requiring surgery. All included studies were rated as good quality (NOS score \u2265 7), indicating low risk of bias. Conclusions: ULD-RT is a highly effective and safe treatment modality for OAL, providing excellent local control with a favorable toxicity profile. These findings support the adoption of ULD-RT as a first-line radiotherapy strategy for indolent OAL. Future prospective trials with longer follow-up and standardized toxicity reporting are warranted to confirm and refine its clinical role.<\/jats:p>","DOI":"10.3390\/cancers17172845","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T16:18:15Z","timestamp":1756484295000},"page":"2845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Outcomes and Safety of Ultra-Low-Dose Radiotherapy for Ocular Adnexal Lymphoma: A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9552-8649","authenticated-orcid":false,"given":"Milo\u0161","family":"Gruji\u0107","sequence":"first","affiliation":[{"name":"Center for Radiation Oncology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Clinical Oncology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Volchenkov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Oncology N.N. Petrov, 197758 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7735-549X","authenticated-orcid":false,"given":"Aidos","family":"Akhmetali","sequence":"additional","affiliation":[{"name":"Outpatient Care Department, Hematology Center LLP, Karaganda Medical University, Karaganda 100000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2146-3381","authenticated-orcid":false,"given":"Marija","family":"\u017divkovi\u0107 Radojevi\u0107","sequence":"additional","affiliation":[{"name":"Center for Radiation Oncology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Clinical Oncology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Milosavljevi\u0107","sequence":"additional","affiliation":[{"name":"Center for Radiation Oncology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Clinical Oncology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7891-7962","authenticated-orcid":false,"given":"Katarina","family":"Jankovi\u0107","sequence":"additional","affiliation":[{"name":"Center for Radiation Oncology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Krasi\u0107","sequence":"additional","affiliation":[{"name":"Center for Radiation Oncology, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Mihajlovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Oncology, University Clinical Center Nis, 18000 Nis, Serbia"},{"name":"Faculty of Medicine, University of Nis, 18000 Nis, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-6655","authenticated-orcid":false,"given":"Mohamed","family":"Shelan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Inselspital Bern, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0731-8041","authenticated-orcid":false,"given":"Luca","family":"Nicosia","sequence":"additional","affiliation":[{"name":"Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, 37034 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8437-3493","authenticated-orcid":false,"given":"Mladen","family":"Marinkovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Radiation Oncology, Institute for Oncology and Radiology of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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