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Circulating tumor cell (CTC) counts and CTC telomerase activity (TA) as prognotic markers of overall survival (OS) in SWOG S0421: Docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer (mCRPC)

Goldkorn, Amir and Vogelzang, Nicholas J. and Fink, Louis M. and Ely, Benjamin and Quinn, David I. and Tangen, Catherine M. and Tai, Yu-Chong and Twardowski, Przemyslaw and Van Veldhuizen, Peter J. and Agarwal, Neeraj and Carducci, Michael Anthony and Monk, J. P. and Garzotto, Mark and Mack, Philip C. and Lara, Primo and Higano, Celestia S. and Hussain, Maha and Cote, Richard J. and Thompson, Ian Murchie (2012) Circulating tumor cell (CTC) counts and CTC telomerase activity (TA) as prognotic markers of overall survival (OS) in SWOG S0421: Docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer (mCRPC). Journal of Clinical Oncology, 30 (30). ISSN 1527-7755. https://resolver.caltech.edu/CaltechAUTHORS:20170208-112200426

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Abstract

Background: CTCs are promising biomarkers in mCRPC, and telomerase activity (TA) is a recognized cancer marker. In this phase III trial we analyzed CTCs using 2 methods: CellSearch for fixed cell enumeration, and a novel Parylene-C slot filter for live CTC capture and TA measurement. Methods: Blood samples (7.5 ml) were drawn at baseline (d1) and pre-cycle 2 (d21) of Rx and shipped overnight for central processing. For CellSearch enumeration, Cox regression was used to evaluate the association between OS, baseline CTC counts, and CTC dynamics (d1 to d21). For TA, filter-trapped cells were lysed and assayed for TA using qPCR-based telomeric repeat amplification. Cox regression evaluated the association between OS and TA overall and within subgroups characterized by good vs. poor (<5 vs. >=5) prognosis baseline CTC counts. For all measurements, receiver operator characteristic (ROC) analysis and characteristics and regression trees (CART) were used to explore further prognostic cutpoints. Results: Samples were obtained from 263 men. Median d1 CTC count was 5, and there was a significant difference in OS for d1 CTC < vs. >=5, hazard ratio (HR) 2.92 (p<0.001) after adjustment for other factors. D1 CTC and OS had ROC AUC of 0.781. In men with low d1 CTC (< 5), an increase in CTC was associated with shorter OS, HR 4.04 (p=0.004); in men with high d1 CTC (>=5), a >=2-fold decrease in CTC was associated with longer OS, HR 0.45 (p=0.012); adjusting for risk factors. For TA, men with baseline CTC >=5 (41% of cohort) who had high CTC TA had HR 1.14 (p<0.005) for OS after adjustment for other factors including CTC counts. CART identified additional risk subgroups based on CTC counts and TA. Conclusions: In this phase III trial, d1 CTC and d1 to d21 CTC dynamics were prognostic of OS after risk factor adjustment, comprising the largest docetaxel-based prospective cohort to date which validates a 5 CTC prognostic threshold and identifies new potentially useful enumeration subgroups. In men with CTCs >=5, TA from cells live-captured on a new slot filter constitutes the first CTC-derived biomarker prognostic of OS in a prospective clinical trial.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://ascopubs.org/doi/abs/10.1200/jco.2012.30.30_suppl.1PublisherArticle
ORCID:
AuthorORCID
Tai, Yu-Chong0000-0001-8529-106X
Additional Information:© 2012 American Society of Clinical Oncology.
Issue or Number:30
Record Number:CaltechAUTHORS:20170208-112200426
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170208-112200426
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74159
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:08 Feb 2017 21:39
Last Modified:03 Oct 2019 16:35

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