EP1038 Ovarian malignancy risk stratification using a third-generation multivariate index assay. (1st November 2019)

• Record Type: Journal Article
• Authors: Zhang, Z; Bullock, RG; Fritsche, H
• Is Part Of: International journal of gynecological cancer. Volume 29(2019)Supplement 4
• Page Start: A546
• Page End: A546
• Publication Date: 2019-11-01
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2019-ESGO.1082
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Introduction/Background: To further extend and improve the utility of two FDA-cleared multivariate index assays for preoperative malignancy risk assessment of adnexal masses, we developed a third generation multivariate index assay MIA3G that stratifies patients with an adnexal mass into three risk groups. A small high-risk (HR) rule-in group captures a majority of the total cancer cases with a clinically actionable positive predictive value (PPV). A low-risk rule-out group includes a significant portion of the remaining test population with a very high negative predictive value (NPV). Methodology: Seven serum protein analytes: apolipoprotein A-1, beta-2 microglobulin, CA125, follicle stimulating hormone, HE4, transferrin (TRF), and transthyretin (TT) were analyzed on samples from four IRB-approved independent multicenter study cohorts (table 1 ). The OVA1 Study set was used for training. Two algorithms and corresponding cutoffs were derived for pre- and post-menopausal patients separately. They were then independently validated on the remaining three study sample sets. In addition to sensitivity/specificity, PPVs/NPVs were estimated after adjusting the pre-test cancer prevalence of the validation sets to 5% for premenopausal and 10% for postmenopausal patients. Results: The results are summarized in table 2 and figure 1 . They were relatively consistent across the 3 validation sets. As an example, for the premenopausal patients in the validation sets, with an assumed prevalence of 5%, the HR group identified <10% of the test population yet captured 52% - 81% of the cancer cases, resulting in a PPV>33%. On the other hand, >64% of the premenopausal samples were assigned to the LR group at an NPV of 99%. MIA3G performed well for stage I/II invasive cancer and multiple histologic subtypes (data not shown). Conclusion: With further validation in a prospective studies, MIA3G could be potentially used in patients with suspicious adnexal masses as part of the decision of surgery. Disclosure: RG Bullock and HA Fritsche are employees of Vermillion Inc. which funded this work. Z Zhang is a consultant for Vermillion Inc. and contributed to this work independent of his affiliation with Johns Hopkins University