{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T03:27:06Z","timestamp":1768447626441,"version":"3.49.0"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pelvic Melanoma relapse occurs in 15% of patients with loco regional metastases, and 25% of cases do not respond to new target-therapy and\/or immunotherapy. Melphalan hypoxic pelvic perfusion may, therefore, be an option for these non-responsive patients. Overall median survival time (MST), stratified for variables, including BRAF V600E mutation and eligibility for treatments with new immunotherapy drugs, was retrospectively assessed in 41 patients with pelvic melanoma loco regional metastases. They had received a total of 175 treatments with Melphalan hypoxic perfusion and cytoreductive excision. Among the 41 patients, 22 (53.7%) patients exhibited a wild-type BRAF genotype, 11 of which were not eligible for immunotherapy. The first treatment resulted in a 97.5% response-rate in the full cohort and a 100% response-rate in the 22 wild-type BRAF patients. MST was 18 months in the full sample, 20 months for the 22 wild-type BRAF patients and 21 months for the 11 wild-type BRAF patients not eligible for immunotherapy. Melphalan hypoxic perfusion is a potentially effective treatment for patients with pelvic melanoma loco regional metastases that requires confirmation in a larger multicenter study.<\/jats:p>","DOI":"10.3390\/ijms18112382","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T11:33:02Z","timestamp":1510227182000},"page":"2382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Does Locoregional Chemotherapy Still Matter in the Treatment of Advanced Pelvic Melanoma?"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8525-084X","authenticated-orcid":false,"given":"Stefano","family":"Guadagni","sequence":"first","affiliation":[{"name":"Department of Applied Clinical Sciences and Biotechnology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giammaria","family":"Fiorentini","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology, Ospedali Riuniti Marche Nord, 61121 Pesaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9652-5148","authenticated-orcid":false,"given":"Marco","family":"Clementi","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5464-7497","authenticated-orcid":false,"given":"Giancarlo","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-2691","authenticated-orcid":false,"given":"Paola","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Chiominto","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Baldoni","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Masedu","sequence":"additional","affiliation":[{"name":"Department of Applied Clinical Sciences and Biotechnology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-3456","authenticated-orcid":false,"given":"Marco","family":"Valenti","sequence":"additional","affiliation":[{"name":"Department of Applied Clinical Sciences and Biotechnology, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ambra Di","family":"Tommaso","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Fabi","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camillo","family":"Aliberti","sequence":"additional","affiliation":[{"name":"Department of Radiology, Institute for the Research and Treatment of Cancer, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Sarti","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology, Ospedali Riuniti Marche Nord, 61121 Pesaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Guadagni","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-8097","authenticated-orcid":false,"given":"Cristina","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Department of Applied Clinical 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Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10555-017-9657-1","article-title":"The impact of melanoma genetics on treatment response and resistance in clinical and experimental studies","volume":"36","author":"Kunz","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4329\/wjr.v5.i2.25","article-title":"Melanoma metastases in the abdomen and pelvis: Frequency and patterns of spread","volume":"5","author":"Trout","year":"2013","journal-title":"World J. Radiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0002-9610(01)00841-8","article-title":"Deliberate hypoxic pelvic and limb chemoperfusion in the treatment of recurrent melanoma","volume":"83","author":"Guadagni","year":"2002","journal-title":"Am. J. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/S1470-2045(16)30368-0","article-title":"Are we there yet? Prolonged MAPK inhibition in BRAF V600-mutant melanoma","volume":"17","author":"Khushalani","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1002\/cncr.28851","article-title":"The nature and management of metastatic melanoma after progression on BRAF inhibitors: Effects of extended BRAF inhibition","volume":"120","author":"Chan","year":"2014","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1200\/JCO.2013.53.0105","article-title":"Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab","volume":"32","author":"Topollian","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1001\/jama.2016.4059","article-title":"Association of pembrolizumab with tumor response and survival among patients with advanced melanoma","volume":"315","author":"Ribas","year":"2016","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/14740338.2016.1175430","article-title":"Pembrolizumab for melanoma-safety profile and future trends","volume":"15","author":"Daud","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s11912-017-0575-8","article-title":"The role of surgery for melanoma in an era of effective systemic therapy","volume":"19","author":"Raigani","year":"2017","journal-title":"Curr. Oncol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1200\/JCO.1999.17.9.2745","article-title":"Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma","volume":"17","author":"Chapman","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_12","first-page":"488","article-title":"Treatment of metastatic melanoma: An overview","volume":"23","author":"Bhatia","year":"2009","journal-title":"Oncology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1097\/00000658-196004000-00024","article-title":"Regional chemotherapy for cancer: Experiences with 116 perfusions","volume":"151","author":"Stehlin","year":"1960","journal-title":"Ann. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Guadagni, S., Palumbo, G., Fiorentini, G., Clementi, M., and Marsili, L. (2017). Surgical versus percutaneous isolated pelvic perfusion (IPP) for advanced melanoma: Comparison in terms of melphalan pharmacokinetic pelvic bio-availability. BMC Res Notes, 10.","DOI":"10.1186\/s13104-017-2738-y"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF02306286","article-title":"Preoperative therapy for advanced pelvic malignancy by isolated pelvic perfusion with the balloon-occlusion technique","volume":"3","author":"Wanebo","year":"1996","journal-title":"Ann. Surg. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/SLA.0b013e318242ebe7","article-title":"Hyperthermic pelvic perfusion with tumor necrosis factor-\u03b1 for locally advanced cancers. Encouraging results of a phase II study","volume":"255","author":"Bonvalot","year":"2012","journal-title":"Ann. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/pcmr.12475","article-title":"The state of melanoma: challenges and opportunities","volume":"29","author":"Merlino","year":"2016","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1002\/cncr.25148","article-title":"Prognostic factors in cutaneous Desmoplastic Melanoma: A study of 252 patients","volume":"116","author":"Murali","year":"2010","journal-title":"Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.jaad.2015.02.1113","article-title":"Metaanalysis of BRAF mutations and clinicopathologic characteristics in primary melanoma","volume":"72","author":"Kim","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pellegrini, C., Di Nardo, L., Cipolloni, G., Martorelli, C., de Padova, M., Antonini, A., Maturo, M.G., del Regno, L., Strafella, S., and Micantonio, T. (2017). Heterogeneity of Braf, Nras, and Tert-Promoter Mutational Status in Multiple Melanomas and association with Mc1r Genotype: Findings from Molecular and immunohistochemical analysis. J. Mol. Diagn.","DOI":"10.1016\/j.jmoldx.2017.10.002"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1002\/cncr.30642","article-title":"Immune checkpoint inhibitors in challenging populations","volume":"123","author":"Johnson","year":"2017","journal-title":"Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s002800050611","article-title":"Mechanisms of enhancement of the antitumour activity of Melphalan by the tumour-blood-flow inhibitor 5,6-dimethylxanthenone-4-acetic acid","volume":"39","author":"Pruijn","year":"1997","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1002\/cncr.24220","article-title":"Efficacy of repeat isolated limb infusion with melphalan and actinomycin D for recurrent melanoma","volume":"115","author":"Kroon","year":"2009","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1097\/CMR.0000000000000359","article-title":"Multicenter, real-life experience with checkpoint inhibitors and targeted therapy agents in advanced melanoma patients in Switzerland","volume":"27","author":"Mangana","year":"2017","journal-title":"Melanoma Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jss.2017.03.066","article-title":"Melphalan hypoxic perfusion with hemofiltration for melanoma locoregional metastases in the pelvis","volume":"215","author":"Guadagni","year":"2017","journal-title":"J. Surg. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s12325-016-0283-z","article-title":"Use patterns and costs of isolated limb perfusion and infusion in the treatment of regional metastatic melanoma: A retrospective database analysis","volume":"33","author":"Ma","year":"2016","journal-title":"Adv. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1200\/JCO.2009.23.4799","article-title":"Final version of 2009 AJCC melanoma staging and classification","volume":"27","author":"Balch","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/jso.23519","article-title":"Factors associated with response, survival, and limb salvage in patients undergoing isolated limb infusion","volume":"109","author":"Steinman","year":"2014","journal-title":"J. Surg. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.yexmp.2012.03.001","article-title":"Competitive allele specific TaqMan PCR for KRAS, BRAF and EGFR mutation detection in clinical formalin fixed paraffin embedded samples","volume":"92","author":"Didelot","year":"2012","journal-title":"Exp. Mol. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/00008390-200302000-00009","article-title":"Hypoxic pelvic and limb perfusion with Melphalan and mitomycin C for recurrent limb melanoma: A pilot study","volume":"13","author":"Guadagni","year":"2003","journal-title":"Melanoma Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ejso.2004.01.009","article-title":"Hemodynamic variations during thoracic and abdominal stop-flow regional chemotherapy","volume":"30","author":"Varrassi","year":"2004","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/CMR.0000000000000367","article-title":"MGMT methylation correlates with melphalan pelvic perfusion survival in stage III melanoma patients: A pilot study","volume":"27","author":"Guadagni","year":"2017","journal-title":"Melanoma Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response valuation criteria in solid tumors: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2382\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:48:48Z","timestamp":1760208528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,9]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11]]}},"alternative-id":["ijms18112382"],"URL":"https:\/\/doi.org\/10.3390\/ijms18112382","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,9]]}}}