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

Kazuo Koyanagi, Steven J. O'Day, Rene Gonzalez, Karl Lewis, William A. Robinson, Thomas T. Amatruda, He Jing Wang, Robert M. Elashoff, Hiroya Takeuchi, Naoyuki Umetani, Dave S.B. Hoon

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Abstract

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.

Original languageEnglish
Pages (from-to)8057-8064
Number of pages8
JournalJournal of Clinical Oncology
Volume23
Issue number31
DOIs
Publication statusPublished - 2005 Dec 1

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Koyanagi, K., O'Day, S. J., Gonzalez, R., Lewis, K., Robinson, W. A., Amatruda, T. T., Wang, H. J., Elashoff, R. M., Takeuchi, H., Umetani, N., & Hoon, D. S. B. (2005). Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma: Outcome prediction in a multicenter trial. Journal of Clinical Oncology, 23(31), 8057-8064. https://doi.org/10.1200/JCO.2005.02.0958