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Ex vivo chemoresponse assay of ovarian cancers predicts clinical outcome.
H. Gallion, W. Christopherson, R. Coleman, T. Herzog, B.-U. Sevin, A. Wells, L. Fiori,
Ovarian Investigator Group; UPMC, Pittsburgh, PA; Mercy Hosp, Pittsburgh, PA; UT Southwestern, Dallas, TX; Washington Univ, St. Louis, MO; Mayo Clinic/Jacksonville, Jacksonville, FL; Precision Therapeutics, Inc., Pittsburgh, PA
Abstract: Background: Advanced ovarian cancer remains without chemotherapeutic cure. Numerous regimens can achieve clinical responses, but each only in a subset of women. The challenge is to predict which regimen an individual will respond to prior to its administration.
Methods: We examined the clinical outcome of 317 women from 9 practices from whom ovarian cancer specimens were tested with an ex vivo chemoresponse assay between 4/30/97 and 4/30/02.
The assay results were scored for sensitivity or resistance based on live cell number after exposure to varied concentrations of each chemotherapeutic regimen, and reported to the referring physician.
Clinical data was compiled by an independent clinical research organization. Cox Proportional Hazard Model analysis identified independent prognostic factors.
Results: Classification into two groups (sensitive and resistant) failed to yield statistically significant differences in progression free interval (PFI).
Reclassification into three groups (sensitive, intermediate, and resistant) and the application of quality filters developed since 1997 was highly predictive of outcome. Of the 317 cases, 135 were treated with the same regimen that had been tested: the hazard ratio (HR) for PFI of ex vivo resistant tumors was 2.9 times (95% CI: 1.4 to 6.3; P<0.01) that of ex vivo sensitive tumors.
The PFI of women whose tumors scored as intermediate fell between those scored as sensitive and those scored as resistant. When analyses were expanded to include all women who received at least one of the drugs tested, the relationship remained robust (HR=2.1; CI: 1.2 to 3.1; P=0.01; N=256).
In the most challenging cohort, recurrent cancer, the HR was 2.6 (CI: 1.1 to 6.5; P<0.05; N=77).
Conclusions: These data strongly suggest that incorporating an ex vivo chemoresponse assay can improve the clinical outcome of individual patients receiving either single or combination chemotherapy regimens.
Abstract No: 5074
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