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.

Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma

“…Based on the validated HMW-MAA antigen detection, 22,23 uveal melanoma CTC count was lower than in most epithelial tumor types, but was in line with previous results obtained in metastatic cutaneous melanoma patients. 18 Our results showed that elevated CTC count, using either a 1 or 2 CTC=7.5 mL positivity threshold, is associated with survival in our prospective Figure 1.…”

“…It has been reported previously in cutaneous melanoma patients, together with its sensitivity and reproducibility. 17,18 Briefly, cells expressing CD146 were immunomagnetically enriched and stained with 4,2-diamidino-2-phenylindole dihydrochloride (DAPI), phycoerythrin-conjugated antibody (clone 9.2.27) that binds to HMW-MAA and a mixture of two allophycocyaninconjugated antibodies to identify leukocytes (CD45, clone HI30) and endothelial cells (CD34, clone 581). To be counted as a melanoma CTC, a cell must have an oval morphology and a nucleus [DAPI (1)], together with a HMW-MAA(1), CD45(2) and CD34(2) phenotype.…”

“…Patient characteristics and outcome were prospectively collected. CTCs (1) were detected in 12 of the 40 included patients (30%, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Among the 26 patients with known detectable mutations, ctDNA was detected and quantified in 22 (84%, range 4-11,421 copies=mL).…”

Clinical Significance of Circulating Tumor Microemboli as a Prognostic Marker in Patients with Pancreatic Ductal Adenocarcinoma

“…The PFS and OS were both shorter in patients with unfavorable CTM. (21,22 ). Besides, the study that demonstrated that CTC numbers were associated with shorter survival in pancreatic cancer had limited cases (20 ).…”

Quantitative changes of melanoma‐associated antigens as a biomarker for targeted therapy response

“…At the moment, there are no existent biomarkers, which could anticipate this phenomenon (3). Longitudinal follow-up of patients and monitoring of circulating tumor cell (CTC) levels could predict treatment failure and help switch to another type of treatment (4)(5)(6).…”