Abstract 4816: OVA1: An in vitro diagnostic multivariate index assay for preoperative assessment of ovarian tumors
Authors: Zhang Zhen , Sokoll Lori , Desimone Chris , Seamon Leigh , Ware Rachel , Goodrich Scott , Podzielinski Iwona , Smith Alan , Santoso Joseph , van Nagell John R. , Chan Daniel W. , Ueland Frederick R. 
Published: February 2011

Abstract
Objectives: We describe the development and validation of OVA1, an in vitro diagnostic multivariate index assay (IVDMIA) that has been recently approved by the FDA for preoperative assessment of the risk of ovarian cancer in women with ovarian tumors to help in deciding who should be referred to a gynecologic oncologist for surgery.
Methods: The OVA1 test combines five immunoassays into a single numerical result, including CA125 II, transthyretin (prealbumin), apolipoprotein A1, beta 2microglobulin, and transferrin. The OVA1 algorithm was derived using prospectively collected samples from women with a pelvic mass who were surgically evaluated for ovarian cancer. OVA1 was then validated in women scheduled for surgery for a known ovarian tumor in a prospective, multi-institutional trial involving 27 primary care and specialty sites throughout the United States. Over half of the patients (52%) were enrolled by non-GO surgeons. The OVA1 results were correlated with the physician assessment (assigned by the enrolling physician after considering all available clinical information) and surgical pathology. Subjects were excluded from analysis if surgery was not performed, pathology report was not available, or the blood specimen was unusable.
Results: The training sample set consisted of 274 samples from the University of Kentucky (including 63 epithelial ovarian cancer (EOC), 27 tumors of low malignant potential (LMP), 3 other ovarian malignancies, and 12 other cancers) and 125 samples from another multiple institution study (including 33 ovarian cancer). The independent validation study enrolled 590 women and 516 were evaluable with a pre-surgical assessment. There were 151 ovarian malignancies (29.3%), including: 96 EOC, 9 non-EOC, 28 LMP, and 18 malignancies metastatic to the ovary (met). The 235 premenopausal women enrolled (45.5%) accounted for 42 ovarian malignancies. The OVA1 test had a sensitivity of 92.5% and a specificity of 42.8% with corresponding PPV at 42.3% and NPV at 92.7%. OVA1 significantly improved the clinician's pre-surgical assessment for both non-GO and GO physicians. Sensitivity improved from 72.2% to 91.7% (95% CI: 83.0-96.1) for non-GO, and 77.5% to 98.9% (95% CI: 93.9-99.8) for GO. The NPV improved from 89.1% to 93.2% (95% CI: 85.9-96.8) for non-GO, and 85.5% to 97.6% (95% CI: 87.7-99.6) for GO. OVA1 correctly identified 70% (non-GO) and 95% (GO) of malignancies missed by the preoperative physician assessment alone. The OVA1 sensitivity by histologic subtype was: EOC 99.0% (95/96), non-EOC 77.8% (7/9), LMP 75.0% (21/28), and met 94.4% (17/18).
Conclusions: In the prospective, multi-institutional trial, the IDVMIA OVA1 correctly identified the majority of patients with ovarian malignancies that were missed by preoperative physician assessment alone, supporting the use of OVA1 to assist in surgical planning and decisions about referral to a gynecologic oncologist before surgery.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4816.