{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:52:49Z","timestamp":1783698769673,"version":"3.55.0"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014835","name":"Istituto Nazionale Tumori IRCCS &quot;Fondazione G. Pascale&quot;","doi-asserted-by":"publisher","award":["M2\/2"],"award-info":[{"award-number":["M2\/2"]}],"id":[{"id":"10.13039\/501100014835","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant\/BRAF wild-type (mut\/wt) and 169 wt\/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt\/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt\/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7\u201318) versus 9 months (95% CI, 6\u201316) and 32 (95% CI, 23\u201349) versus 27 months (95% CI, 16\u201335), respectively). Irrespectively of mutational status, a longer OS was significantly associated with normal LDH, &lt;3 metastatic sites, lower white blood cell and platelet count, lower neutrophil-to-lymphocyte (N\/L) ratio. Our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant MM.<\/jats:p>","DOI":"10.3390\/cancers13030475","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T12:03:57Z","timestamp":1611662637000},"page":"475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["No Impact of NRAS Mutation on Features of Primary and Metastatic Melanoma or on Outcomes of Checkpoint Inhibitor Immunotherapy: An Italian Melanoma Intergroup (IMI) Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Michele","family":"Guida","sequence":"first","affiliation":[{"name":"Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-4615","authenticated-orcid":false,"given":"Nicola","family":"Bartolomeo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Quaglino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Dermatologic Clinic, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-3190","authenticated-orcid":false,"given":"Gabriele","family":"Madonna","sequence":"additional","affiliation":[{"name":"Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione \u201cG. Pascale\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Pigozzo","sequence":"additional","affiliation":[{"name":"Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 31033 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Di Giacomo","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Minisini","sequence":"additional","affiliation":[{"name":"Department of Oncology, ASUFC University Hospital, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-4897","authenticated-orcid":false,"given":"Marco","family":"Tucci","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, University of Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Spagnolo","sequence":"additional","affiliation":[{"name":"Skin Cancer Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Occelli","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera Santa Croce e Carle di Cuneo SC Oncologia, 12100 Cuneo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1870-3380","authenticated-orcid":false,"given":"Laura","family":"Ridolfi","sequence":"additional","affiliation":[{"name":"Department of Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Queirolo","sequence":"additional","affiliation":[{"name":"Division of Melanoma Sarcoma and Rare Tumors, IEO European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"De Risi","sequence":"additional","affiliation":[{"name":"Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Quaresmini","sequence":"additional","affiliation":[{"name":"Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Gambale","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9191-9124","authenticated-orcid":false,"given":"Vanna","family":"Chiaron Sileni","sequence":"additional","affiliation":[{"name":"Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 31033 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione \u201cG. Pascale\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Stigliano","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Dermatologic Clinic, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7982-7788","authenticated-orcid":false,"given":"Sabino","family":"Strippoli","sequence":"additional","affiliation":[{"name":"Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Italian Melanoma Intergroup (IMI) Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1056\/NEJMoa1502583","article-title":"The genetic Evolution of Melanoma from precursor lesions","volume":"373","author":"Shain","year":"2015","journal-title":"N. 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