Assessment of prognostic circulating tumor cells in a phase III trial of adjuvant immunotherapy after complete resection of stage IV melanoma.

Hoshimoto S, Faries MB, Morton DL, Shingai T, Kuo C, Wang HJ, Elashoff R, Mozzillo N, Kelley MC, Thompson JF, Lee JE, Hoon DS
Ann Surg. 2012 255 (2): 357-62

PMID: 22202581 · PMCID: PMC3320770 · DOI:10.1097/SLA.0b013e3182380f56

OBJECTIVE - To verify circulating tumor cell (CTC) prognostic utility in stage IV resected melanoma patients in a prospective international phase III clinical trial.

BACKGROUND - Our studies of melanoma patients in phase II clinical trials demonstrated prognostic significance for CTCs in patients with AJCC stage IV melanoma. CTCs were assessed to determine prognostic utility in follow-up of disease-free stage IV patients pre- and during treatment.

METHODS - After complete metastasectomy, patients were prospectively enrolled in a randomized trial of adjuvant therapy with a whole-cell melanoma vaccine, Canvaxin, plus Bacille Calmette-Guerin (BCG) versus placebo plus BCG. Blood specimens obtained pretreatment (n = 244) and during treatment (n = 214) were evaluated by quantitative real-time reverse-transcriptase polymerase chain reaction (qPCR) for expression of MART-1, MAGE-A3, and PAX3 mRNA biomarkers. Univariate and multivariate Cox analyses examined CTC biomarker expression with respect to clinicopathological variables.

RESULTS - CTC biomarker(s) (≥ 1) was detected in 54% of patients pretreatment and in 86% of patients over the first 3 months. With a median follow-up of 21.9 months, 71% of patients recurred and 48% expired. CTC levels were not associated with known prognostic factors or treatment arm. In multivariate analysis, pretreatment CTC (> 0 vs. 0 biomarker) status was significantly associated with disease-free survival (DFS; HR 1.64, P = 0.002) and overall survival (OS; HR 1.53, P = 0.028). Serial CTC (>0 vs. 0 biomarker) status was also significantly associated with DFS (HR 1.91, P = 0.02) and OS (HR 2.57, P = 0.012).

CONCLUSION - CTC assessment can provide prognostic discrimination before and during adjuvant treatment for resected stage IV melanoma patients.

MeSH Terms (24)

Adult Aged Antigens, Neoplasm Biomarkers, Tumor Cancer Vaccines Chemotherapy, Adjuvant Double-Blind Method Female Humans Male MART-1 Antigen Melanoma Middle Aged Multivariate Analysis Neoplasm Proteins Neoplasm Staging Neoplastic Cells, Circulating Paired Box Transcription Factors PAX3 Transcription Factor Prognosis Real-Time Polymerase Chain Reaction Recurrence Reverse Transcriptase Polymerase Chain Reaction Survival Analysis

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