Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial
Year: 2014
Type: article
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 (p = 0.001) 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 (p = 0.009). 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 towards molecular CTC-based precision cancer management.
Source: International Journal of Cancer
DOI: 10.1002/ijc.29212
Authors: 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 C. Mack, Primo Lara, Celestia S. Higano, Maha Hussain, Nicholas J. Vogelzang, Ian M. Thompson, Richard J. Cote, David I. Quinn
Institutions: University of Southern California, USC Norris Comprehensive Cancer Center, Fred Hutch Cancer Center, California Institute of Technology, City Of Hope National Medical Center, City of Hope, University of Kansas, The University of Kansas Cancer Center, University of Utah, Huntsman Cancer Institute, Johns Hopkins University, The Ohio State University, Portland VA Medical Center, University of California, Davis, Seattle Cancer Care Alliance, University of Washington, University of Michigan, U-M Rogel Cancer Center, Comprehensive Cancer Centers of Nevada, The University of Texas at San Antonio Health Science Center, University of Miami
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1033243903, G1063390784, G117886320, G1202672505, G1216887118, G1219254266, G1257093844, G1257575315, G1312097577, G1331445602, G1343089328, G136433756, G1375689152, G1391839138, G1469275664, G1545560008, G1548551769, G158054334, G1653272384, G1687173946, G1701879424, G176778339, G1790576020, G1814228702, G188931153, ECOG-ACRIN Network Group Operations Center, G1911575068, G1938688226, G1958973285, G1985252453, G2043432835, G2057923966, G2064543036, Scott & White Community Clinical Oncology Program, G2160369479, G2197455483, G220021360, G2201816905, G2235549394, G2237949143, G2276667821, G2334490894, G2345882982, G2419449687, G2435896781, G2485941414, G251042051, G2562936776, G2679961467, G268786457, MAREK'S DISEASE VIRUS--TRANSFORMATION AND ONCOGENESIS, G2733372321, G2750730928, COLUMBIA UNIVERSITY SOUTHWEST ONCOLOGY GROUP PROGRAM, G2847983442, G2875799307, Ozark Health Ventures, LLC dba Cancer Research for the Ozarks, GRAND RAPIDS CLINICAL ONCOLOGY PROGRAM, SOUTHWEST ONCOLOGY GROUP STATISTICAL CENTER, G3126600779, G3159066211, G3189416178, G3239274266, G3242537740, Southeast Cancer Control Consortium, Inc, G3277991276, G3295642875, G3309877080, G3334379738, G3337849518, G3350348941, G3478738010, G3484997517, G3491596100, G3497039781, G3521018462, G3601756391, City of Hope Southwest Oncology Group Clinical Trials, G36541222, G3705794112, G3710026009, G3717917512, G3737421695, SWOG Network Group Operations Center of the NCTN, G379387698, G3896758871, G3939550896, G3953184339, G3989676687, G3996959562, G4132498144, G413878341, G4249097859, G425646771, Southwest Oncology Group, G444114835, G4466285564, Southwest Oncology Group, G4491827645, G4493846124, G449830344, G4499290131, G4499432180, G4527800867, SOUTHWEST ONCOLOGY GROUP, G4935167430, SOUTHWEST ONCOLOGY GROUP, G5073861092, G5154223049, G5187432406, G5264753430, G532004893, G543303160, G5503582138, G5543746979, G5566132837, G5761683024, G5765316850, G6081897200, SOUTHWEST ONCOLOGY GROUP, G6203648436, G6211207823, G6245294507, G6493065596, Cancer and Leukemia Group B, G6702782149, G6717414950, G6723594983, G6777566682, G6782300252, G7061256793, G7140878794, G7152607643, G7222907299, G7230571265, CENTRAL ILLINOIS COMMUNITY CLINICAL ONCOLOGY PROGRAM, G7520596819, G7593726543, Virginia Mason Community Clinical Oncology Program, G763325562, G7755328110, G776903742, G7772521268, Nevada Cancer Research foundation-Community Clinical Oncology Program, G7860541851, G7926913928, G8006406963, G8036334546, G8143312774, Eastern Cooperative Oncology Group Operations Office, G8413228103, G860872252, SOUTHWEST ONCOLOGY GROUP, G8740717309, G8777682367, G8800314823, PARTICIPATE AS MEMBER OF SOUTHWEST ONCOLOGY GROUP, G8937348795, G9000076717, G9000083837, G9000105589, G9000128743, Cancer Center Support Grant P30, University of Southern California Norris Comprehensive Cancer Center Support Grant (CCSG), G910064448, G933283670, G937543590, G963778558, G964706321, G971274320, G973482110
OpenAlex ID: W1848925583