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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Circulating Neoplastic Cells
Multicenter Studies
Melanoma
Reverse Transcriptase Polymerase Chain Reaction
Recurrence
Therapeutics
Survival
Real-Time Polymerase Chain Reaction
N-Acetylgalactosaminyltransferases
Transcription Factor 3
MART-1 Antigen
Melanoma-Specific Antigens
Homeobox Genes
Differentiation Antigens
Proportional Hazards Models
Neoplasms
Multivariate Analysis
Odds Ratio
Messenger RNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma : Outcome prediction in a multicenter trial. / Koyanagi, Kazuo; O'Day, Steven J.; Gonzalez, Rene; Lewis, Karl; Robinson, William A.; Amatruda, Thomas T.; Wang, He Jing; Elashoff, Robert M.; Takeuchi, Hiroya; Umetani, Naoyuki; Hoon, Dave S B.

In: Journal of Clinical Oncology, Vol. 23, No. 31, 2005, p. 8057-8064.

Research output: Contribution to journalArticle

Koyanagi, K, O'Day, SJ, Gonzalez, R, Lewis, K, Robinson, WA, Amatruda, TT, Wang, HJ, Elashoff, RM, Takeuchi, H, Umetani, N & Hoon, DSB 2005, 'Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma: Outcome prediction in a multicenter trial', Journal of Clinical Oncology, vol. 23, no. 31, pp. 8057-8064. https://doi.org/10.1200/JCO.2005.02.0958
Koyanagi, Kazuo ; O'Day, Steven J. ; Gonzalez, Rene ; Lewis, Karl ; Robinson, William A. ; Amatruda, Thomas T. ; Wang, He Jing ; Elashoff, Robert M. ; Takeuchi, Hiroya ; Umetani, Naoyuki ; Hoon, Dave S B. / Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma : Outcome prediction in a multicenter trial. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 31. pp. 8057-8064.
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title = "Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma: Outcome prediction in a multicenter trial",
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.",
author = "Kazuo Koyanagi and O'Day, {Steven J.} and Rene Gonzalez and Karl Lewis and Robinson, {William A.} and Amatruda, {Thomas T.} and Wang, {He Jing} and Elashoff, {Robert M.} and Hiroya Takeuchi and Naoyuki Umetani and Hoon, {Dave S B}",
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T1 - Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma

T2 - Outcome prediction in a multicenter trial

AU - Koyanagi, Kazuo

AU - O'Day, Steven J.

AU - Gonzalez, Rene

AU - Lewis, Karl

AU - Robinson, William A.

AU - Amatruda, Thomas T.

AU - Wang, He Jing

AU - Elashoff, Robert M.

AU - Takeuchi, Hiroya

AU - Umetani, Naoyuki

AU - Hoon, Dave S B

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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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