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Phase III validation using PLCO specimens of a consensus panel of ovarian cancer biomarkers developed by SPORE/EDRN investigators

Principal Investigator
Name
Daniel W. Cramer
Degrees
-
Institution
Brigham and Women's Hospital / Harvard Medical School
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2005-0009
Initial CDAS Request Approval
Aug 17, 2005
Title
Phase III validation using PLCO specimens of a consensus panel of ovarian cancer biomarkers developed by SPORE/EDRN investigators
Summary
Ovarian cancer is the most lethal gynecological malignancy among North American women. Most patients at diagnosis have stage III/IV disease and only 25% of them will survive 5-years. However, for stage I/II disease, survival can be as high as 90%. This suggests that early detection could offer a promising approach to improve the long-term survival of ovarian cancer patients. There has been interest in adapting serum CA125, approved for ovarian cancer monitoring, as a screening test. However, CA125 may have poor sensitivity for early-staged disease and for mucinous or clear cell types of ovarian cancer. In addition, CA125 may be elevated by a number of benign conditions, lowering its specificity. To minimize the number of women who may require secondary screening or laparoscopy to evaluate an abnormal screening test, the sensitivity and specificity of the test may need to approach at least 80% and 98% respectively. Since it is unlikely any single marker will achieve this target, a reasonable approach is to develop a panel of biomarkers.
Aims

Beginning with panels of biomarkers for ovarian cancer developed independently by Specialized Programs of Research Excellence (SPORE) and Early Detection Research Network (EDRN) investigators, we will: 1). Retest the combined biomarkers on a newly-assembled test set of 160 cases with pre-operative bloods representing major histologic types and including 80 early-staged and 80 late-staged cases, 160 controls with benign disease, and 480 general population controls. 2). Identify the most informative 5 biomarkers in a consensus panel that can be evaluated with standard ELISAs, requiring only 0.5 ml of sera as well as a more inclusive set of markers that could be evaluated on two Luminex panels requiring 0.10ml. 3). Using 1 ml of sera from the PLCO subjects, apply the consensus ELISA and Luminex panels to all prediagnostic specimens from all PLCO participants who subsequently developed ovarian cancer and from all longitudinal specimens from 10 matched controls who did not develop ovarian cancer for each case. 4). Using any residual sera, apply high end mass spectrometry and other discovery techniques to seek new markers especially in pre-clinical cases who were false negative or controls who were false positive by the panels. Our hypothesis is that a panel of biomarkers will have better performance characteristics as a screening test for pre-clinical ovarian cancer than any single marker.

Collaborators

Andre Kajdacsy-Balla (University of Illinois - Chicago)
Andrew Godwin (Fox Chase Cancer Center)
David Fishman (NYU Cancer Institute)
Eleftherios Diamandis (Mount Sinai Hospital)
Anna Lokshin (University of Pittsburgh)
Martin McIntosh (FHCRC)
Nicole Urban (FHCRC)
Ed Partridge (University of Alabama)
Paul Cairns (Fox Chase Cancer Center)
Robert Bast (University of Texas MD Anderson Cancer)
Saundra Buys (University of Utah/Boise)
Eugene Sobel (Friends Research Institute)
Steven Skates (Massachusetts General Hospital)
Zoreh Davanipour (Friends Research Institute)

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