Serial monitoring of circulating tumor cells predicts outcome of induction biochemotherapy plus maintenance biotherapy for metastatic melanoma

Kazuo Koyanagi, Steven J. O'Day, Peter Boasberg, Michael B. Atkins, He Jing Wang, Rene Gonzalez, Karl Lewis, John A. Thompson, Clay M. Anderson, Jose Lutzky, Thomas T. Amatruda, Evan M Hersh, Jon Richards, Jeffrey S. Weber, Dave S B Hoon

Research output: Contribution to journalArticle

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Abstract

Purpose: Molecular biomarkers in blood are promising for assessment of tumor progression and treatment response. We hypothesized that serial monitoring of circulating tumor cells (CTC) with the use of multimarker quantitative real-time reverse transcriptase-PCR assays could be a surrogate predictor of outcome for melanoma patients enrolled in a multicenter phase II clinical trial of biochemotherapy (BCT) combined with maintenance biotherapy (mBT). Experimental Design: Blood specimens were collected from 87 patients before and during induction BCT and mBT for stage IV melanoma. Expression of five melanoma-associated CTC biomarkers (MART-1, GalNAc-T, PAX-3, MAGE-A3, and Mitf) was assessed by quantitative real-time reverse transcriptase-PCR, and correlated with treatment response and disease outcome. Results: The number of positive CTC biomarkers decreased overall during induction BCT (P < 0.0001). CTC biomarker detection after two cycles of BCT was correlated with treatment response (P = 0.005) and overall survival (P = 0.001): an increase in the number of CTC biomarkers was associated with poor response (P = 0.006) and overall survival (P < 0.0001). Multivariate analyses with the use of a Cox proportional hazards model identified the change in CTC biomarkers after two cycles of BCT as an independent prognostic factor for disease progression (risk ratio, 12.6; 95% confidence interval, 4.78-33.4; P < 0.0001) and overall survival (risk ratio, 6.11; 95% confidence interval, 2.37-15.7; P = 0.0005). Conclusion: Serial monitoring of CTC during induction BCT may be useful for predicting therapeutic efficacy and disease outcome in patients receiving BCT and mBT for stage IV melanoma.

Original languageEnglish (US)
Pages (from-to)2402-2408
Number of pages7
JournalClinical Cancer Research
Volume16
Issue number8
DOIs
StatePublished - Apr 15 2010

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Circulating Neoplastic Cells
Biological Therapy
Melanoma
Tumor Biomarkers
Maintenance
Reverse Transcriptase Polymerase Chain Reaction
Survival
Real-Time Polymerase Chain Reaction
Odds Ratio
Confidence Intervals
Phase II Clinical Trials
Therapeutics
Proportional Hazards Models
Disease Progression
Research Design
Multivariate Analysis
Biomarkers

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Serial monitoring of circulating tumor cells predicts outcome of induction biochemotherapy plus maintenance biotherapy for metastatic melanoma. / Koyanagi, Kazuo; O'Day, Steven J.; Boasberg, Peter; Atkins, Michael B.; Wang, He Jing; Gonzalez, Rene; Lewis, Karl; Thompson, John A.; Anderson, Clay M.; Lutzky, Jose; Amatruda, Thomas T.; Hersh, Evan M; Richards, Jon; Weber, Jeffrey S.; Hoon, Dave S B.

In: Clinical Cancer Research, Vol. 16, No. 8, 15.04.2010, p. 2402-2408.

Research output: Contribution to journalArticle

Koyanagi, K, O'Day, SJ, Boasberg, P, Atkins, MB, Wang, HJ, Gonzalez, R, Lewis, K, Thompson, JA, Anderson, CM, Lutzky, J, Amatruda, TT, Hersh, EM, Richards, J, Weber, JS & Hoon, DSB 2010, 'Serial monitoring of circulating tumor cells predicts outcome of induction biochemotherapy plus maintenance biotherapy for metastatic melanoma', Clinical Cancer Research, vol. 16, no. 8, pp. 2402-2408. https://doi.org/10.1158/1078-0432.CCR-10-0037
Koyanagi, Kazuo ; O'Day, Steven J. ; Boasberg, Peter ; Atkins, Michael B. ; Wang, He Jing ; Gonzalez, Rene ; Lewis, Karl ; Thompson, John A. ; Anderson, Clay M. ; Lutzky, Jose ; Amatruda, Thomas T. ; Hersh, Evan M ; Richards, Jon ; Weber, Jeffrey S. ; Hoon, Dave S B. / Serial monitoring of circulating tumor cells predicts outcome of induction biochemotherapy plus maintenance biotherapy for metastatic melanoma. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 8. pp. 2402-2408.
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abstract = "Purpose: Molecular biomarkers in blood are promising for assessment of tumor progression and treatment response. We hypothesized that serial monitoring of circulating tumor cells (CTC) with the use of multimarker quantitative real-time reverse transcriptase-PCR assays could be a surrogate predictor of outcome for melanoma patients enrolled in a multicenter phase II clinical trial of biochemotherapy (BCT) combined with maintenance biotherapy (mBT). Experimental Design: Blood specimens were collected from 87 patients before and during induction BCT and mBT for stage IV melanoma. Expression of five melanoma-associated CTC biomarkers (MART-1, GalNAc-T, PAX-3, MAGE-A3, and Mitf) was assessed by quantitative real-time reverse transcriptase-PCR, and correlated with treatment response and disease outcome. Results: The number of positive CTC biomarkers decreased overall during induction BCT (P < 0.0001). CTC biomarker detection after two cycles of BCT was correlated with treatment response (P = 0.005) and overall survival (P = 0.001): an increase in the number of CTC biomarkers was associated with poor response (P = 0.006) and overall survival (P < 0.0001). Multivariate analyses with the use of a Cox proportional hazards model identified the change in CTC biomarkers after two cycles of BCT as an independent prognostic factor for disease progression (risk ratio, 12.6; 95{\%} confidence interval, 4.78-33.4; P < 0.0001) and overall survival (risk ratio, 6.11; 95{\%} confidence interval, 2.37-15.7; P = 0.0005). Conclusion: Serial monitoring of CTC during induction BCT may be useful for predicting therapeutic efficacy and disease outcome in patients receiving BCT and mBT for stage IV melanoma.",
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T1 - Serial monitoring of circulating tumor cells predicts outcome of induction biochemotherapy plus maintenance biotherapy for metastatic melanoma

AU - Koyanagi, Kazuo

AU - O'Day, Steven J.

AU - Boasberg, Peter

AU - Atkins, Michael B.

AU - Wang, He Jing

AU - Gonzalez, Rene

AU - Lewis, Karl

AU - Thompson, John A.

AU - Anderson, Clay M.

AU - Lutzky, Jose

AU - Amatruda, Thomas T.

AU - Hersh, Evan M

AU - Richards, Jon

AU - Weber, Jeffrey S.

AU - Hoon, Dave S B

PY - 2010/4/15

Y1 - 2010/4/15

N2 - Purpose: Molecular biomarkers in blood are promising for assessment of tumor progression and treatment response. We hypothesized that serial monitoring of circulating tumor cells (CTC) with the use of multimarker quantitative real-time reverse transcriptase-PCR assays could be a surrogate predictor of outcome for melanoma patients enrolled in a multicenter phase II clinical trial of biochemotherapy (BCT) combined with maintenance biotherapy (mBT). Experimental Design: Blood specimens were collected from 87 patients before and during induction BCT and mBT for stage IV melanoma. Expression of five melanoma-associated CTC biomarkers (MART-1, GalNAc-T, PAX-3, MAGE-A3, and Mitf) was assessed by quantitative real-time reverse transcriptase-PCR, and correlated with treatment response and disease outcome. Results: The number of positive CTC biomarkers decreased overall during induction BCT (P < 0.0001). CTC biomarker detection after two cycles of BCT was correlated with treatment response (P = 0.005) and overall survival (P = 0.001): an increase in the number of CTC biomarkers was associated with poor response (P = 0.006) and overall survival (P < 0.0001). Multivariate analyses with the use of a Cox proportional hazards model identified the change in CTC biomarkers after two cycles of BCT as an independent prognostic factor for disease progression (risk ratio, 12.6; 95% confidence interval, 4.78-33.4; P < 0.0001) and overall survival (risk ratio, 6.11; 95% confidence interval, 2.37-15.7; P = 0.0005). Conclusion: Serial monitoring of CTC during induction BCT may be useful for predicting therapeutic efficacy and disease outcome in patients receiving BCT and mBT for stage IV melanoma.

AB - Purpose: Molecular biomarkers in blood are promising for assessment of tumor progression and treatment response. We hypothesized that serial monitoring of circulating tumor cells (CTC) with the use of multimarker quantitative real-time reverse transcriptase-PCR assays could be a surrogate predictor of outcome for melanoma patients enrolled in a multicenter phase II clinical trial of biochemotherapy (BCT) combined with maintenance biotherapy (mBT). Experimental Design: Blood specimens were collected from 87 patients before and during induction BCT and mBT for stage IV melanoma. Expression of five melanoma-associated CTC biomarkers (MART-1, GalNAc-T, PAX-3, MAGE-A3, and Mitf) was assessed by quantitative real-time reverse transcriptase-PCR, and correlated with treatment response and disease outcome. Results: The number of positive CTC biomarkers decreased overall during induction BCT (P < 0.0001). CTC biomarker detection after two cycles of BCT was correlated with treatment response (P = 0.005) and overall survival (P = 0.001): an increase in the number of CTC biomarkers was associated with poor response (P = 0.006) and overall survival (P < 0.0001). Multivariate analyses with the use of a Cox proportional hazards model identified the change in CTC biomarkers after two cycles of BCT as an independent prognostic factor for disease progression (risk ratio, 12.6; 95% confidence interval, 4.78-33.4; P < 0.0001) and overall survival (risk ratio, 6.11; 95% confidence interval, 2.37-15.7; P = 0.0005). Conclusion: Serial monitoring of CTC during induction BCT may be useful for predicting therapeutic efficacy and disease outcome in patients receiving BCT and mBT for stage IV melanoma.

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