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

Sojun Hoshimoto, Mark B. Faries, Donald L. Morton, Tatsushi Shingai, Christine Kuo, He Jing Wang, Robert Elashoff, Nicola Mozzillo, Mark C. Kelley, John F. Thompson, Jeffrey E. Lee, Dave S B Hoon

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Abstract

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. Study registration ID# NCT00052156.

Original languageEnglish
Pages (from-to)357-362
Number of pages6
JournalAnnals of Surgery
Volume255
Issue number2
DOIs
Publication statusPublished - Feb 2012

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Circulating Neoplastic Cells
Immunotherapy
Melanoma
Biomarkers
Tumor Biomarkers
Multivariate Analysis
Metastasectomy
Therapeutics
Phase III Clinical Trials
Phase II Clinical Trials
Reverse Transcriptase Polymerase Chain Reaction
Disease-Free Survival
Real-Time Polymerase Chain Reaction
Vaccines
Placebos
Messenger RNA

ASJC Scopus subject areas

  • Surgery

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Assessment of prognostic circulating tumor cells in a phase III trial of adjuvant immunotherapy after complete resection of stage IV melanoma. / Hoshimoto, Sojun; Faries, Mark B.; Morton, Donald L.; Shingai, Tatsushi; Kuo, Christine; Wang, He Jing; Elashoff, Robert; Mozzillo, Nicola; Kelley, Mark C.; Thompson, John F.; Lee, Jeffrey E.; Hoon, Dave S B.

In: Annals of Surgery, Vol. 255, No. 2, 02.2012, p. 357-362.

Research output: Contribution to journalArticle

Hoshimoto, S, Faries, MB, Morton, DL, Shingai, T, Kuo, C, Wang, HJ, Elashoff, R, Mozzillo, N, Kelley, MC, Thompson, JF, Lee, JE & Hoon, DSB 2012, 'Assessment of prognostic circulating tumor cells in a phase III trial of adjuvant immunotherapy after complete resection of stage IV melanoma', Annals of Surgery, vol. 255, no. 2, pp. 357-362. https://doi.org/10.1097/SLA.0b013e3182380f56
Hoshimoto, Sojun ; Faries, Mark B. ; Morton, Donald L. ; Shingai, Tatsushi ; Kuo, Christine ; Wang, He Jing ; Elashoff, Robert ; Mozzillo, Nicola ; Kelley, Mark C. ; Thompson, John F. ; Lee, Jeffrey E. ; Hoon, Dave S B. / Assessment of prognostic circulating tumor cells in a phase III trial of adjuvant immunotherapy after complete resection of stage IV melanoma. In: Annals of Surgery. 2012 ; Vol. 255, No. 2. pp. 357-362.
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abstract = "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. Study registration ID# NCT00052156.",
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T1 - Assessment of prognostic circulating tumor cells in a phase III trial of adjuvant immunotherapy after complete resection of stage IV melanoma

AU - Hoshimoto, Sojun

AU - Faries, Mark B.

AU - Morton, Donald L.

AU - Shingai, Tatsushi

AU - Kuo, Christine

AU - Wang, He Jing

AU - Elashoff, Robert

AU - Mozzillo, Nicola

AU - Kelley, Mark C.

AU - Thompson, John F.

AU - Lee, Jeffrey E.

AU - Hoon, Dave S B

PY - 2012/2

Y1 - 2012/2

N2 - 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. Study registration ID# NCT00052156.

AB - 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. Study registration ID# NCT00052156.

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