Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer

Steven J. Cohen, Cornelis J.A. Punt, Nicholas Iannotti, Bruce H. Saidman, Kert D. Sabbath, Nashat Y. Gabrail, Joel Picus, Michael Morse, Edith Mitchell, M. Craig Miller, Gerald V. Doyle, Henk Tissing, Leon W.M.M. Terstappen, Neal J. Meropol

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    Abstract

    Purpose: As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.Patients and

    Methods: In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.

    Results: Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.

    Conclusion: The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.

    LanguageEnglish
    Pages3213-3221
    Number of pages9
    JournalJournal of clinical oncology
    Volume26
    Issue number19
    DOIs
    StatePublished - 2008

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    Circulating Neoplastic Cells
    Disease-Free Survival
    Colorectal Neoplasms
    Survival
    Neoplasms
    Immunomagnetic Separation
    Therapeutics
    Multicenter Studies

    Keywords

    • METIS-251916

    Cite this

    Cohen, S. J., Punt, C. J. A., Iannotti, N., Saidman, B. H., Sabbath, K. D., Gabrail, N. Y., ... Meropol, N. J. (2008). Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer. Journal of clinical oncology, 26(19), 3213-3221. DOI: 10.1200/JCO.2007.15.8923
    Cohen, Steven J. ; Punt, Cornelis J.A. ; Iannotti, Nicholas ; Saidman, Bruce H. ; Sabbath, Kert D. ; Gabrail, Nashat Y. ; Picus, Joel ; Morse, Michael ; Mitchell, Edith ; Miller, M. Craig ; Doyle, Gerald V. ; Tissing, Henk ; Terstappen, Leon W.M.M. ; Meropol, Neal J./ Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer. In: Journal of clinical oncology. 2008 ; Vol. 26, No. 19. pp. 3213-3221
    @article{45b0359322274e988a44ead38f8fa0b1,
    title = "Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer",
    abstract = "Purpose: As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.Patients and Methods: In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.Results: Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.Conclusion: The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.",
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    author = "Cohen, {Steven J.} and Punt, {Cornelis J.A.} and Nicholas Iannotti and Saidman, {Bruce H.} and Sabbath, {Kert D.} and Gabrail, {Nashat Y.} and Joel Picus and Michael Morse and Edith Mitchell and Miller, {M. Craig} and Doyle, {Gerald V.} and Henk Tissing and Terstappen, {Leon W.M.M.} and Meropol, {Neal J.}",
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    doi = "10.1200/JCO.2007.15.8923",
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    Cohen, SJ, Punt, CJA, Iannotti, N, Saidman, BH, Sabbath, KD, Gabrail, NY, Picus, J, Morse, M, Mitchell, E, Miller, MC, Doyle, GV, Tissing, H, Terstappen, LWMM & Meropol, NJ 2008, 'Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer' Journal of clinical oncology, vol 26, no. 19, pp. 3213-3221. DOI: 10.1200/JCO.2007.15.8923

    Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer. / Cohen, Steven J.; Punt, Cornelis J.A.; Iannotti, Nicholas; Saidman, Bruce H.; Sabbath, Kert D.; Gabrail, Nashat Y.; Picus, Joel; Morse, Michael; Mitchell, Edith; Miller, M. Craig; Doyle, Gerald V.; Tissing, Henk; Terstappen, Leon W.M.M.; Meropol, Neal J.

    In: Journal of clinical oncology, Vol. 26, No. 19, 2008, p. 3213-3221.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer

    AU - Cohen,Steven J.

    AU - Punt,Cornelis J.A.

    AU - Iannotti,Nicholas

    AU - Saidman,Bruce H.

    AU - Sabbath,Kert D.

    AU - Gabrail,Nashat Y.

    AU - Picus,Joel

    AU - Morse,Michael

    AU - Mitchell,Edith

    AU - Miller,M. Craig

    AU - Doyle,Gerald V.

    AU - Tissing,Henk

    AU - Terstappen,Leon W.M.M.

    AU - Meropol,Neal J.

    PY - 2008

    Y1 - 2008

    N2 - Purpose: As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.Patients and Methods: In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.Results: Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.Conclusion: The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.

    AB - Purpose: As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.Patients and Methods: In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.Results: Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.Conclusion: The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.

    KW - METIS-251916

    U2 - 10.1200/JCO.2007.15.8923

    DO - 10.1200/JCO.2007.15.8923

    M3 - Article

    VL - 26

    SP - 3213

    EP - 3221

    JO - Journal of clinical oncology

    T2 - Journal of clinical oncology

    JF - Journal of clinical oncology

    SN - 0732-183X

    IS - 19

    ER -