title: Clinical features and response to systemic therapy in a historical cohort of advanced or unresectable mucosal melanoma.
abstract: There are very few data available regarding the pattern of first metastases in resected mucosal melanomas (MMs) as well as the response of advanced MM to cytotoxic therapy. A retrospective, single-institution cohort was assembled of all patients with advanced/unresectable MM between 1995 and 2012 who had received systemic therapy with available imaging (N=81). Responses to first-line and second-line systemic therapy were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The relationship between response, overall survival, and clinical covariates was investigated using Cox proportional hazards regression. Primary sites included anorectal (N=31, 38%), vulvovaginal (N=28, 35%), head and neck (N=21, 26%), and gallbladder (N=1, 1%) mucosa. Seven percent of patients had their first relapse in the brain. Cytotoxic therapy represented 82 and 51% of first-line and second-line regimens. The best response achieved in the first-line setting was similar for single-agent [10%; 95% confidence interval (CI): 1-32%] and combination alkylator therapy (8%; 95% CI: 2-21%). Median overall survival from first-line treatment was 10.3 months (95% CI: 8.7-13.9 months). Patients with elevated lactic dehydrogenase [hazard ratio (HR): 1.87, 95% CI: 1.10-3.19, P=0.020] and Eastern Cooperative Oncology Group performance status 1-2 (HR: 1.69, 95% CI: 1.05-2.72, P=0.030) had a higher risk of death, whereas patients with 12-week objective responses had a lower risk of death (HR: 0.12, 95% CI: 0.04-0.41, P<0.001). Cytotoxic systemic therapy has modest activity in advanced/unresectable MM, belying its adjuvant benefit. Patients whose tumors have an objective response to therapy have a lower probability of death. Brain imaging should be considered in routine surveillance.
authors: aMelanoma and Immunotherapeutics Service, Department of Medicine bDepartment of Radiology cDepartment of Epidemiology and Biostatistics dDepartment of Surgery, Memorial Sloan Kettering Cancer Center eWeill Cornell Medical College fColumbia University Medical Center, New York, New York, USA.
authors: Alexander N
authors: AN
authors: Shoushtari
authors: Mark J
authors: MJ
authors: Bluth
authors: Debra A
authors: DA
authors: Goldman
authors: Christiana
authors: C
authors: Bitas
authors: Robert A
authors: RA
authors: Lefkowitz
authors: Michael A
authors: MA
authors: Postow
authors: Rodrigo R
authors: RR
authors: Munhoz
authors: Gauri
authors: G
authors: Buchar
authors: Robert H
authors: RH
authors: Hester
authors: Jacqueline A
authors: JA
authors: Romero
authors: Laura J
authors: LJ
authors: Fitzpatrick
authors: Martin R
authors: MR
authors: Weiser
authors: Katherine S
authors: KS
authors: Panageas
authors: Jedd D
authors: JD
authors: Wolchok
authors: Paul B
authors: PB
authors: Chapman
authors: Richard D
authors: RD
authors: Carvajal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006305:Health Status Indicators; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009092:Mucous Membrane; D009154:Mutation; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D066066:Response Evaluation Criteria in Solid Tumors; D012189:Retrospective Studies; D015996:Survival Rate; D014625:Vaginal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014846:Vulvar Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000074322:Antineoplastic Agents, Immunological; D008565:Membrane Proteins; D007770:L-Lactate Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human