Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial

Amir Goldkorn, Benjamin Ely, Catherine M. Tangen, Yu Chong Tai, Tong Xu, Hongli Li, Przemyslaw Twardowski, Peter J. Van Veldhuizen, Neeraj Agarwal, Michael A. Carducci, J. Paul Monk, Mark Garzotto, Philip Mack, Primo N Lara, Celestia S. Higano, Maha Hussain, Nicholas J. Vogelzang, Ian M. Thompson, Richard J. Cote, David I. Quinn

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J). Cox regression was used to assess baseline (pre-treatment) TA versus OS, and recursive partitioning was used to explore potential prognostic subgroups and to generate Kaplan-Meier (KM) OS curves. Samples were obtained from 263 patients and generated 215 TA measures. In patients with baseline CTC count ≥5 (47% of patients), higher CTC TA was associated with hazard ratio 1.14 (p50.001) for OS after adjusting for other clinical covariates including CTC counts and serum PSA at study entry. Recursive partitioning identified new candidate risk groups with KM OS curve separation based on CTC counts and TA. Notably, in men with an intermediate range baseline CTC count (6-54 CTCs/7.5 ml), low versus high CTC TA was associated with median survival of 19 versus 12 months, respectively (p50.009). Baseline telomerase activity from CTCs live-captured on a new slot microfilter is the first CTC-derived candidate biomarker prognostic of OS in a large patient subgroup in a prospective clinical trial. CTC telomerase activity thus merits further study and validation as a step.

Original languageEnglish (US)
Pages (from-to)1856-1862
Number of pages7
JournalInternational Journal of Cancer
Volume136
Issue number8
DOIs
StatePublished - Apr 15 2015

Fingerprint

Circulating Neoplastic Cells
Telomerase
Castration
Prostatic Neoplasms
Survival
Cell Count
Kaplan-Meier Estimate
bis(2,3,3,3-tetrachloropropyl) ether
Biomarkers
Validation Studies

Keywords

  • Biomarker
  • Circulating tumor cells
  • Prognosis
  • Prostate cancer
  • Telomerase activity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421 : A phase III metastatic castration resistant prostate cancer trial. / Goldkorn, Amir; Ely, Benjamin; Tangen, Catherine M.; Tai, Yu Chong; Xu, Tong; Li, Hongli; Twardowski, Przemyslaw; Van Veldhuizen, Peter J.; Agarwal, Neeraj; Carducci, Michael A.; Monk, J. Paul; Garzotto, Mark; Mack, Philip; Lara, Primo N; Higano, Celestia S.; Hussain, Maha; Vogelzang, Nicholas J.; Thompson, Ian M.; Cote, Richard J.; Quinn, David I.

In: International Journal of Cancer, Vol. 136, No. 8, 15.04.2015, p. 1856-1862.

Research output: Contribution to journalArticle

Goldkorn, A, Ely, B, Tangen, CM, Tai, YC, Xu, T, Li, H, Twardowski, P, Van Veldhuizen, PJ, Agarwal, N, Carducci, MA, Monk, JP, Garzotto, M, Mack, P, Lara, PN, Higano, CS, Hussain, M, Vogelzang, NJ, Thompson, IM, Cote, RJ & Quinn, DI 2015, 'Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial', International Journal of Cancer, vol. 136, no. 8, pp. 1856-1862. https://doi.org/10.1002/ijc.29212
Goldkorn, Amir ; Ely, Benjamin ; Tangen, Catherine M. ; Tai, Yu Chong ; Xu, Tong ; Li, Hongli ; Twardowski, Przemyslaw ; Van Veldhuizen, Peter J. ; Agarwal, Neeraj ; Carducci, Michael A. ; Monk, J. Paul ; Garzotto, Mark ; Mack, Philip ; Lara, Primo N ; Higano, Celestia S. ; Hussain, Maha ; Vogelzang, Nicholas J. ; Thompson, Ian M. ; Cote, Richard J. ; Quinn, David I. / Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421 : A phase III metastatic castration resistant prostate cancer trial. In: International Journal of Cancer. 2015 ; Vol. 136, No. 8. pp. 1856-1862.
@article{d127ba6469114417ab19d6849a4fbdf8,
title = "Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial",
abstract = "Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J). Cox regression was used to assess baseline (pre-treatment) TA versus OS, and recursive partitioning was used to explore potential prognostic subgroups and to generate Kaplan-Meier (KM) OS curves. Samples were obtained from 263 patients and generated 215 TA measures. In patients with baseline CTC count ≥5 (47{\%} of patients), higher CTC TA was associated with hazard ratio 1.14 (p50.001) for OS after adjusting for other clinical covariates including CTC counts and serum PSA at study entry. Recursive partitioning identified new candidate risk groups with KM OS curve separation based on CTC counts and TA. Notably, in men with an intermediate range baseline CTC count (6-54 CTCs/7.5 ml), low versus high CTC TA was associated with median survival of 19 versus 12 months, respectively (p50.009). Baseline telomerase activity from CTCs live-captured on a new slot microfilter is the first CTC-derived candidate biomarker prognostic of OS in a large patient subgroup in a prospective clinical trial. CTC telomerase activity thus merits further study and validation as a step.",
keywords = "Biomarker, Circulating tumor cells, Prognosis, Prostate cancer, Telomerase activity",
author = "Amir Goldkorn and Benjamin Ely and Tangen, {Catherine M.} and Tai, {Yu Chong} and Tong Xu and Hongli Li and Przemyslaw Twardowski and {Van Veldhuizen}, {Peter J.} and Neeraj Agarwal and Carducci, {Michael A.} and Monk, {J. Paul} and Mark Garzotto and Philip Mack and Lara, {Primo N} and Higano, {Celestia S.} and Maha Hussain and Vogelzang, {Nicholas J.} and Thompson, {Ian M.} and Cote, {Richard J.} and Quinn, {David I.}",
year = "2015",
month = "4",
day = "15",
doi = "10.1002/ijc.29212",
language = "English (US)",
volume = "136",
pages = "1856--1862",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421

T2 - A phase III metastatic castration resistant prostate cancer trial

AU - Goldkorn, Amir

AU - Ely, Benjamin

AU - Tangen, Catherine M.

AU - Tai, Yu Chong

AU - Xu, Tong

AU - Li, Hongli

AU - Twardowski, Przemyslaw

AU - Van Veldhuizen, Peter J.

AU - Agarwal, Neeraj

AU - Carducci, Michael A.

AU - Monk, J. Paul

AU - Garzotto, Mark

AU - Mack, Philip

AU - Lara, Primo N

AU - Higano, Celestia S.

AU - Hussain, Maha

AU - Vogelzang, Nicholas J.

AU - Thompson, Ian M.

AU - Cote, Richard J.

AU - Quinn, David I.

PY - 2015/4/15

Y1 - 2015/4/15

N2 - Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J). Cox regression was used to assess baseline (pre-treatment) TA versus OS, and recursive partitioning was used to explore potential prognostic subgroups and to generate Kaplan-Meier (KM) OS curves. Samples were obtained from 263 patients and generated 215 TA measures. In patients with baseline CTC count ≥5 (47% of patients), higher CTC TA was associated with hazard ratio 1.14 (p50.001) for OS after adjusting for other clinical covariates including CTC counts and serum PSA at study entry. Recursive partitioning identified new candidate risk groups with KM OS curve separation based on CTC counts and TA. Notably, in men with an intermediate range baseline CTC count (6-54 CTCs/7.5 ml), low versus high CTC TA was associated with median survival of 19 versus 12 months, respectively (p50.009). Baseline telomerase activity from CTCs live-captured on a new slot microfilter is the first CTC-derived candidate biomarker prognostic of OS in a large patient subgroup in a prospective clinical trial. CTC telomerase activity thus merits further study and validation as a step.

AB - Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J). Cox regression was used to assess baseline (pre-treatment) TA versus OS, and recursive partitioning was used to explore potential prognostic subgroups and to generate Kaplan-Meier (KM) OS curves. Samples were obtained from 263 patients and generated 215 TA measures. In patients with baseline CTC count ≥5 (47% of patients), higher CTC TA was associated with hazard ratio 1.14 (p50.001) for OS after adjusting for other clinical covariates including CTC counts and serum PSA at study entry. Recursive partitioning identified new candidate risk groups with KM OS curve separation based on CTC counts and TA. Notably, in men with an intermediate range baseline CTC count (6-54 CTCs/7.5 ml), low versus high CTC TA was associated with median survival of 19 versus 12 months, respectively (p50.009). Baseline telomerase activity from CTCs live-captured on a new slot microfilter is the first CTC-derived candidate biomarker prognostic of OS in a large patient subgroup in a prospective clinical trial. CTC telomerase activity thus merits further study and validation as a step.

KW - Biomarker

KW - Circulating tumor cells

KW - Prognosis

KW - Prostate cancer

KW - Telomerase activity

UR - http://www.scopus.com/inward/record.url?scp=84922661468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922661468&partnerID=8YFLogxK

U2 - 10.1002/ijc.29212

DO - 10.1002/ijc.29212

M3 - Article

C2 - 25219358

AN - SCOPUS:84922661468

VL - 136

SP - 1856

EP - 1862

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 8

ER -