Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma: outcome prediction in a multicenter trial

K Koyanagi, SJ O'Day, R Gonzalez, K Lewis… - Journal of clinical …, 2005 - ascopubs.org
K Koyanagi, SJ O'Day, R Gonzalez, K Lewis, WA Robinson, TT Amatruda, HJ Wang…
Journal of clinical oncology, 2005ascopubs.org
Purpose Circulating tumor cells (CTCs) in blood may be important in assessing tumor
progression and treatment response. We hypothesized that quantitative real-time reverse
transcriptase polymerase chain reaction using multimarker mRNA assays could detect CTCs
and be used as a surrogate predictor of outcome in patients receiving neoadjuvant
biochemotherapy (BC) for melanoma. Patients and Methods Blood specimens were
collected at four sampling points from 63 patients enrolled on a prospective multicenter …
Purpose
Circulating tumor cells (CTCs) in blood may be important in assessing tumor progression and treatment response. We hypothesized that quantitative real-time reverse transcriptase polymerase chain reaction using multimarker mRNA assays could detect CTCs and be used as a surrogate predictor of outcome in patients receiving neoadjuvant biochemotherapy (BC) for melanoma.
Patients and Methods
Blood specimens were collected at four sampling points from 63 patients enrolled on a prospective multicenter phase II trial of BC before and after surgical treatment of American Joint Committee on Cancer stage III melanoma. Each specimen was assessed by quantitative real-time reverse transcriptase polymerase chain reaction for expression of four melanoma-associated markers: melanoma antigen recognized by T cells 1; β1 → 4-N-acetylgalactosaminyltransferase; paired box homeotic gene transcription factor 3; and melanoma antigen gene-A3 family, and the changes of CTCs during treatment and prognostic effect of CTCs after overall treatment on recurrence and survival were investigated.
Results
At a median postoperative follow-up time of 30.4 months, 44 (70%) patients were clinically disease free. In relapse-free patients, the number of detected markers significantly decreased during preoperative BC (P = .036), during postoperative BC (P = .002), and during overall treatment (P < .0001). Marker detection after overall treatment was associated with significant decreases in relapse-free and overall survival (P < .0001). By multivariate analysis using a Cox proportional-hazards model, the number of markers detected after overall treatment was a significant independent prognostic factor for overall survival (risk ratio, 12.6; 95% CI, 3.16 to 50.5; P = .0003).
Conclusion
Serial monitoring of CTCs in blood may be useful for indicating systemic subclinical disease and predicting outcome of patients receiving neoadjuvant BC for metastatic melanoma.
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