{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:59:52Z","timestamp":1788274792261,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Objective: To assess oncological and ophthalmological outcomes after international referral of uveal melanoma patients for proton therapy. Materials and Methods: This is a retrospective study among Dutch uveal melanoma patients who were treated in Switzerland with 60.0 CGE proton therapy (in 4 fractions) from 1987 to 2019. All patients were ineligible for brachytherapy due to tumour size and\/or proximity to the optic nerve. Time-to-event analyses were performed using Kaplan\u2013Meier\u2019s methodology and Cox proportional hazards models. Results: There were 103 patients (104 eyes) with a median largest tumour diameter of 19 mm (range 6\u201326 mm). Tumours were localised centrally (11%), mid-peripherally (65%) or peripherally (34%). Median follow-up was 7 years. Five-year local control, distant metastasis-free survival and eye preservation rates were 94%, 70% and 81% respectively. At five years, severe, moderate and mild visual impairment was observed in respectively 79%, 4% and 6% of the patients. Larger tumour volumes and more central tumour localisation were associated with severe visual impairment. After correction for these factors, dose to the macula, optic disc and retina, but not optic nerve was significantly associated with severe visual impairment. Conclusion: International referral for proton therapy yielded good tumour control and eye preservation rates, but risk of distant metastasis and severe visual impairment were substantial, possibly due to the selection of advanced tumour stages and\/or central localisation. Dose to the macula may be more relevant than dose to the optic nerve for preservation of visual acuity, which is relevant for the treatment planning of proton therapy.<\/jats:p>","DOI":"10.3390\/cancers13246241","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T01:20:41Z","timestamp":1639444841000},"page":"6241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Clinical Outcomes after International Referral of Uveal Melanoma Patients for Proton Therapy"],"prefix":"10.3390","volume":"13","author":[{"given":"Marina","family":"Marinkovic","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart J.","family":"Pors","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke P.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Schalenbourg","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, FAA, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Zografos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, FAA, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Pica","sequence":"additional","affiliation":[{"name":"Proton therapy Center, Paul Scherrer Institute, ETH Domain, 5232 Villigen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hrbacek","sequence":"additional","affiliation":[{"name":"Proton therapy Center, Paul Scherrer Institute, ETH Domain, 5232 Villigen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd G.","family":"Van Duinen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. H. Khanh","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaco C.","family":"Bleeker","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coen R. N.","family":"Rasch","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2261-3820","authenticated-orcid":false,"given":"Martine J.","family":"Jager","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorius P. M.","family":"Luyten","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-4753","authenticated-orcid":false,"given":"Nanda","family":"Horeweg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41572-020-0158-0","article-title":"Uveal melanoma","volume":"6","author":"Jager","year":"2020","journal-title":"Nat. Rev. Dis. 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