{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:00:11Z","timestamp":1793678411373,"version":"4.5.1"},"reference-count":30,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"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>Purpose: Peripapillary choroidal melanoma provides a unique challenge; proximity to visually important structures, such as the optic disc and fovea, confers a high risk for the development of maculopathy and optic neuropathy, leading to poorer visual outcomes with most forms of radiotherapy. Ocular proton therapy (OPT) requires an aperture to shape the beam to the tumour. An aperture \u2018notch\u2019 may minimise damage to the optic disc and\/or the fovea. This study aims to explore if there are any additional advantages to incorporating a notch over the optic nerve beam area. Design: Retrospective audit (cohort study). Participants: Participants included eighty-three patients treated at Liverpool with proton beam therapy from January 2012 to March 2020 for their peripapillary choroidal melanoma. All had a minimum of two and a half years of follow-up vision data; this was to ensure there was enough visual acuity assessment data to perform sufficient analysis. Patients excluded had choroidal melanoma situated over 3 mm from the optic disc, as these were unlikely to have an aperture notch. Methods: A retrospective audit was undertaken in accordance with the Declaration of Helsinki, and registered with the Royal Liverpool Hospitals audit department (audit reference number: Ophth\/SE\/2024-25\/25). Data was collated from the Liverpool Ocular Oncology database, clinic letters and the individual proton beam 3D plans. Robust statistical analysis using a mixed effects model was used to explore associations between notched beams and vision loss and complications. Main Outcome Measures: The primary outcome measure is visual acuity loss post-proton beam therapy. Secondary outcome measures were enucleation and other complication rates. Results: Analysis shows that at 10 years post-OPT, there would be an expected 0.058 (p = 0.077) logMAR of vision saved using a notch for the optic disc compared to no notch (normal apertures); this is considered clinically significant. This cohort also loses vision at a slower rate than other cases. No other predictors were found to be statistically significant for loss of vision, and notched beams showed no advantage in reducing rates of complications. Conclusions: There is some evidence of a trend that utilising a notch for optic disc does show long-term vision benefit; it demonstrates a clinically significant benefit in patients with peripapillary choroidal melanoma.<\/jats:p>","DOI":"10.3390\/cancers17223684","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:05:31Z","timestamp":1763463931000},"page":"3684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Outcomes Following Treatment with Notched Proton Beams for Peripapillary Choroidal Melanomas"],"prefix":"10.3390","volume":"17","author":[{"given":"Gulmeena","family":"Hussain","sequence":"first","affiliation":[{"name":"Liverpool Ocular Oncology Centre, St Paul\u2019s Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1409-0521","authenticated-orcid":false,"given":"Jonathan","family":"Lam","sequence":"additional","affiliation":[{"name":"Liverpool Ocular Oncology Centre, St Paul\u2019s Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Eleuteri","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Clinical Engineering, Royal Liverpool University Hospital, Prescot St., Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Mortimer","sequence":"additional","affiliation":[{"name":"National Eye Proton Therapy Centre, The Clatterbridge Cancer Centre, Wirral CH63 4JY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-2924","authenticated-orcid":false,"given":"Andrzej","family":"Kacperek","sequence":"additional","affiliation":[{"name":"National Eye Proton Therapy Centre, The Clatterbridge Cancer Centre, Wirral CH63 4JY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertil","family":"Damato","sequence":"additional","affiliation":[{"name":"Liverpool Ocular Oncology Centre, St Paul\u2019s Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Heimann","sequence":"additional","affiliation":[{"name":"Liverpool Ocular Oncology Centre, St Paul\u2019s Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8208-5009","authenticated-orcid":false,"given":"Rumana","family":"Hussain","sequence":"additional","affiliation":[{"name":"Liverpool Ocular Oncology Centre, St Paul\u2019s Eye Unit, Royal Liverpool University Hospital, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/s41416-021-01274-4","article-title":"Impact of COVID-19 pandemic on eye cancer care in United Kingdom","volume":"124","author":"Wang","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s40487-018-0056-8","article-title":"Uveal Melanoma: A Review of the Literature","volume":"6","author":"Singh","year":"2018","journal-title":"Oncol. Ther."},{"key":"ref_3","unstructured":"MelanomaUK (2023, January 08). Ocular Melanoma. Available online: https:\/\/www.melanomauk.org.uk\/ocular-melanoma-om."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/eye.2015.51","article-title":"Prognosis of uveal melanoma based on race in 8100 patients: The 2015 Doyne Lecture","volume":"29","author":"Shields","year":"2015","journal-title":"Eye"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/0974-620X.94718","article-title":"Choroidal melanoma","volume":"5","author":"Singh","year":"2012","journal-title":"Oman J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s43856-022-00082-y","article-title":"Long-term relative survival in uveal melanoma: A systematic review and meta-analysis","volume":"2","author":"Herrspiegel","year":"2022","journal-title":"Commun. Med."},{"key":"ref_7","first-page":"462","article-title":"Progression of ocular melanoma metastasis to the liver: The 2012 Zimmerman lecture","volume":"131","author":"Grossniklaus","year":"2013","journal-title":"J. Am. Med. Assoc. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zemba, M., Dumitrescu, O.M., Gheorghe, A.G., Radu, M., Ionescu, M.A., Vatafu, A., and Dinu, V. (2023). Ocular Complications of Radiotherapy in Uveal Melanoma. Cancers, 15.","DOI":"10.3390\/cancers15020333"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/s41433-022-02178-0","article-title":"Proton beam radiotherapy for choroidal and ciliary body melanoma in the UK-national audit of referral patterns of 1084 cases","volume":"37","author":"Hussain","year":"2023","journal-title":"Eye"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.apradiso.2008.06.012","article-title":"Protontherapy of eye tumours in the UK: A review of treatment at Clatterbridge","volume":"67","author":"Kacperek","year":"2009","journal-title":"Appl. Radiat. Isot."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"392","DOI":"10.5114\/jcb.2019.87407","article-title":"Complications and adverse events of plaque brachytherapy for ocular melanoma","volume":"11","author":"Peddada","year":"2019","journal-title":"J. Contemp. Brachytherapy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.ijrobp.2005.01.016","article-title":"Proton beam radiotherapy of choroidal melanoma: The Liverpool-Clatterbridge experience","volume":"62","author":"Damato","year":"2005","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_13","first-page":"249","article-title":"Recurrence of choroidal melanoma after Ru-106 brachytherapy","volume":"117","author":"Bogdali","year":"2016","journal-title":"Klin. Ocz."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.5732\/cjc.010.10529","article-title":"Proton therapy in clinical practice","volume":"30","author":"Liu","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.sjopt.2013.06.014","article-title":"Proton beam radiotherapy of uveal melanoma","volume":"27","author":"Damato","year":"2013","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/sj.bjc.6602754","article-title":"Proton beam therapy","volume":"93","author":"Levin","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_17","unstructured":"International Atomic Energy Agency (2024). Absorbed Dose Determination in External Beam Radiotherapy, International Atomic Energy Agency."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Harrell, F. (2015). Regression Modeling Strategies, Springer. [2nd ed.].","DOI":"10.1007\/978-3-319-19425-7"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ajo.2018.01.025","article-title":"A 12-Year Study of Slotted Palladium-103 Plaque Radiation Therapy for Choroidal Melanoma: Near, Touching, or Surrounding the Optic Nerve","volume":"188","author":"Maheshwari","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1159\/000518975","article-title":"Outcomes following Notched Ruthenium-106 Plaque Brachytherapy for Juxtapapillary Choroidal Melanomas","volume":"7","author":"Sobti","year":"2021","journal-title":"Ocul. Oncol. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1007\/s00417-017-3703-0","article-title":"Juxtapapillary and circumpapillary choroidal melanoma: Globe-sparing treatment outcomes with iodine-125 notched plaque brachytherapy","volume":"255","author":"Hegde","year":"2017","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3129\/i08-177","article-title":"Stereotactic radiotherapy in the treatment of juxtapapillary choroidal melanoma: 2-Year follow-up","volume":"44","author":"Somani","year":"2009","journal-title":"Can. J. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1136\/bjo.2008.153429","article-title":"Stereotactic radiotherapy for treatment of juxtapapillary choroidal melanoma: 3-Year follow-up","volume":"93","author":"Krema","year":"2009","journal-title":"Br. J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1136\/bjophthalmol-2012-302808","article-title":"A comparison between 125Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma","volume":"97","author":"Krema","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.pdpdt.2017.10.018","article-title":"Photodynamic therapy as initial treatment for small choroidal melanomas","volume":"20","author":"Jmor","year":"2017","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10792-020-01594-z","article-title":"Good long-term visual outcomes of parapapillary choroidal melanoma patients treated with proton therapy: A comparative study","volume":"41","author":"Pica","year":"2021","journal-title":"Int. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.ajo.2014.02.032","article-title":"Proton beam therapy of parapapillary choroidal melanoma","volume":"157","author":"Riechardt","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ajo.2017.11.008","article-title":"Efficacy and Safety of Low-Dose Iodine Plaque Brachytherapy for Juxtapapillary Choroidal Melanoma","volume":"186","author":"Oellers","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/s41433-022-02200-5","article-title":"Early anti-VEGF treatment for radiation maculopathy and optic neuropathy: Lessons learned","volume":"37","author":"Powell","year":"2023","journal-title":"Eye"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1167\/iovs.64.7.35","article-title":"Randomized Trial of Treat-and-Extend Intravitreal Aflibercept for Radiation Retinopathy: 1-Year Outcomes","volume":"64","author":"Ali","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/22\/3684\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:22:55Z","timestamp":1763464975000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/22\/3684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,18]]},"references-count":30,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cancers17223684"],"URL":"https:\/\/doi.org\/10.3390\/cancers17223684","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,18]]}}}