{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:07Z","timestamp":1787027767210,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"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>Background\/Objectives: Primary gynecological melanomas are rare malignancies with lower survival rates compared to cutaneous melanomas. Both preclinical and clinical data support the evidence that mucosal melanomas are photon-radioresistant but responsive to carbon ion radiotherapy (CIRT). The aim of this study is to assess, in a real-world cohort, the effectiveness and tolerability of radical CIRT in patients with inoperable gynecological mucosal melanoma. Methods: This is a real-world study aimed to assess the effectiveness and the safety of CIRT in this setting. We defined as the primary endpoints the objective response rate (ORR) and the clinical benefit (CB). The secondary endpoints included the actuarial local control rate (LC) assessed after 1 year and 2 years and the toxicity scored according to CTCAE v.5. Actuarial outcomes were analyzed using the Kaplan\u2013Meier method, while potential predictors were investigated through the Log-rank test. Results: Between 2017 and 2023, eleven Caucasian patients underwent pelvic CIRT (total dose 68.8 GyRBE) for mucosal malignant melanoma of the vulva or the vagina. With a median follow-up of 18 months, we observed an ORR of 82% and a CB of 100%. LC at 1 and 2 years was 100% and 86%, respectively, and among the factors analyzed for their potential impact on LC, age &lt; 60 years seems to be a potential predictor (p = 0.014). The treatment was well tolerated, with only one case of acute grade 3 erythema and, in the late phase, one case of grade 3 erythema and grade 3 urethral toxicity. Conclusions: CIRT was effective and safe for gynecological melanomas. Larger collaborative cohort studies and longer follow-ups are needed to take a step forward in comprehending the correct management of this disease.<\/jats:p>","DOI":"10.3390\/cancers16244147","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T06:29:30Z","timestamp":1733984970000},"page":"4147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Investigating the Local Effectiveness of Carbon Ion Radiotherapy for Unresectable Female Genital Tract Melanomas: A Preliminary Real-World Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1595-104X","authenticated-orcid":false,"given":"Amelia","family":"Barcellini","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"},{"name":"Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3531-9885","authenticated-orcid":false,"given":"Giulia","family":"Fontana","sequence":"additional","affiliation":[{"name":"Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Vai","sequence":"additional","affiliation":[{"name":"Medical Physics Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Damiano","family":"Aletti","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Surgery, IRCCS European Institute of Oncology, 20141 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8690-9420","authenticated-orcid":false,"given":"Alexandra","family":"Charalampopoulou","sequence":"additional","affiliation":[{"name":"Hadron Academy PhD Course, University School for Advanced Studies (IUSS), 27100 Pavia, Italy"},{"name":"Radiobiology Unit, Development and Research Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Chiellino","sequence":"additional","affiliation":[{"name":"Department of Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Ditto","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"},{"name":"Department of Gynecologic Oncology, Centro di Riferimento Oncologico, National Cancer Institute, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6734-739X","authenticated-orcid":false,"given":"Fabio","family":"Landoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy"},{"name":"Division of Gynecologic Surgery, IRCCS Fondazione San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3315-2580","authenticated-orcid":false,"given":"Laura Deborah","family":"Locati","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"},{"name":"Medical Oncology Unit, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8451-429X","authenticated-orcid":false,"given":"Giorgia","family":"Mangili","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-1747","authenticated-orcid":false,"given":"Fabio","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Humanitas San Pio X, 20159 Milan, Italy"},{"name":"Department of Biomedical Science, Humanitas University, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Piccolo","sequence":"additional","affiliation":[{"name":"Radiotherapy Unit, Ospedale di Circolo Fondazione Macchi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Franzetti","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Imparato","sequence":"additional","affiliation":[{"name":"Radiology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Raspagliesi","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6495-8574","authenticated-orcid":false,"given":"Ester","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, Clinical Department, CNAO National Center for Oncological Hadrontherapy, 27100 Pavia, Italy"},{"name":"Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ygyno.2018.04.562","article-title":"Melanoma of the lower genital tract: Prognostic factors and treatment modalities","volume":"150","author":"Gadducci","year":"2018","journal-title":"Gynecol. 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