title: Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma.
abstract: The incidence of melanoma is increasing worldwide. Advances in targeted agents and immunotherapy have improved outcomes in metastatic disease, but biomarkers are required to optimize treatment. We determined the prevalence of circulating tumor cells (CTCs) and explored their utility as prognostic and pharmacodynamic biomarkers. A total of 101 patients with metastatic cutaneous melanoma were recruited prospectively. CTC number was determined using the CellSearch platform and melanoma kits in samples taken at baseline and serially during treatment. CTC numbers ranged between 0 and 36 per 7.5 ml blood; 26% of patients had ≥ 2 CTCs. Baseline CTC number was prognostic for median overall survival (OS) in univariate analysis (2.6 vs. 7.2 months (P<0.011) for patients with ≥ 2 CTCs vs. <2 CTCs, respectively). In multivariate analysis, CTC number was an independent prognostic biomarker of OS (hazard ratio (HR) 2.403, 95% confidence interval (CI) 1.303-4.430, P=0.005). Patients receiving treatment in whom CTC number remained ≥ 2 CTCs during treatment had shorter median OS than those who maintained <2 CTCs (7 vs. 10 months, HR 0.34, 95% CI 0.14-0.81, log-rank test P=0.015). In conclusion, CTC number in metastatic cutaneous melanoma patients is prognostic for OS with a cutoff of 2 CTCs per 7.5 ml blood. CTC number measured before and throughout treatment provided additional prognostic information. Larger studies are warranted to confirm CTC biomarker utility in melanoma patients.
authors.affiliation: Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Khoja
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Cong
authors.initials: C
authors.lastname: Zhou
authors.forename: Matthew
authors.initials: M
authors.lastname: Lancashire
authors.forename: Jessica
authors.initials: J
authors.lastname: Booth
authors.forename: Jeff
authors.initials: J
authors.lastname: Cummings
authors.forename: Raffaele
authors.initials: R
authors.lastname: Califano
authors.forename: Glen
authors.initials: G
authors.lastname: Clack
authors.forename: Andrew
authors.initials: A
authors.lastname: Hughes
authors.forename: Caroline
authors.initials: C
authors.lastname: Dive
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / Q000378:metabolism / Q000556:secondary*; D008875:Middle Aged; D015999:Multivariate Analysis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D011933:Reagent Kits, Diagnostic; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D011933:Reagent Kits, Diagnostic