Effectiveness of a Multivariate Index Assay in the Preoperative Assessment of Ovarian Tumors

Ueland, Frederick R.; DeSimone, Christopher P.; Seamon, Leigh G.; Miller, Rachel; Goodrich, S.; Podzielinski, Iwona; Sokoll, Lori J.; Smith, Austin E.; Nagell, J.R. van; Zhang, Zhen

doi:10.1097/aog.0b013e31821b5118

Cited by 214 publications

(185 citation statements)

References 26 publications

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“…These findings thus add confidence to the discovery and partly support the validity of the markers used in the Ova1 test. Whilst the performance of the non‐CA125 Ova1 markers without CA125 has not been evaluated directly, one study showed that the Ova1 test detected over 50% of malignancies missed by CA125 alone 28. Without inclusion of physician's assessment, the sensitivity and specificity of CA125 alone (cut‐off 35 U/mL) were 77 and 73%, respectively, versus 93 and 43% using the Ova1 test.…”

Section: Discussionmentioning

confidence: 99%

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies

Timms

Arslan-Low

Kabir

et al. 2014

Proteomics Clinical Apps

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PurposeOvarian cancer is a devastating disease and biomarkers for its early diagnosis are urgently required. Serum may be a valuable source of biomarkers that may be revealed by proteomic profiling. Herein, complementary serum protein profiling strategies were employed for discovery of biomarkers that could discriminate cases of malignant and benign ovarian cancer.Experimental designIdentically collected and processed serum samples from 22 cases of invasive epithelial ovarian cancer, 45 benign ovarian neoplasms, and 64 healthy volunteers were subjected to immunodepletion and protein equalization coupled to 2D‐DIGE/MS and multidimensional fractionation coupled to SELDI‐TOF profiling with MS/MS for protein identification. Selected candidates were verified by ELISA in samples from malignant (n = 70) and benign (n = 89) cases and combined marker panels tested against serum CA125.ResultsBoth profiling platforms were complementary in identifying biomarker candidates, four of which (A1AT, SLPI, APOA4, VDBP) significantly discriminated malignant from benign cases. However, no combination of markers was as good as CA125 for diagnostic accuracy. SLPI was further tested as an early marker using prediagnosis serum samples. While it rose in cases toward diagnosis, it did not discriminate prediagnosis cases from controls.Conclusions and clinical relevanceThe candidate biomarkers warrant further validation in independent sample sets.

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Section: Discussionmentioning

confidence: 99%

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies

Timms

Arslan-Low

Kabir

et al. 2014

Proteomics Clinical Apps

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“…5,6 A total of 1110 subjects were prospectively enrolled at 44 sites across the United States, including primary care women's health clinics, general obstetrics and gynecology group practices, gynecologic oncology practices, community and universitybased hospitals, and health maintenance organizations. Institutional review board approval was obtained from each site.…”

Section: Methodsmentioning

confidence: 99%

“…5,6 Biomarker measurements were performed according to the MIA Instructions for Use at Quest Diagnostics, Inc (Chantilly, VA) or the Division of Clinical Chemistry, Department of Pathology, Johns Hopkins Medical Institutions. The MIA is a FDAcleared, assay that incorporates CA125 (CA125-II), transferrin, transthyretin (prealbumin), apolipoprotein A1, and beta-2-microglobulin.…”

Section: Methodsmentioning

confidence: 99%

“…These biomarker results were transformed by the OvaCalc software (Vermillion, Inc., Austin, TX) using a proprietary multivariate algorithm to generate an ovarian malignancy risk score as described previously. 5 The algorithm renders a single risk score from 0.0 to 10.0, and subjects were stratified as high risk with MIA scores 5.0 (premenopausal) or 4.4 (postmenopausal). For CA125 measurement, the same value used for MIA calculation was used for individual analysis, and compared with clinical cutoff values in accordance with published ACOG referral criteria of 200 units/mL for premenopausal women or >35 units/mL for postmenopausal women.…”

Section: Methodsmentioning

confidence: 99%

“…These triage tools are not screening tests, which are designed to detect disease in asymptomatic patients. The multivariate index assay (MIA, OVA1) is a multiple biomarker test that was cleared for use in clinical practice by the Food and Drug Administration (FDA) in 2009 based on a high sensitivity and negative predictive value for identifying ovarian malignancy in a clinical utility study reported by Ueland et al 5 The high sensitivity and negative predictive value for ovarian malignancy were confirmed in an independent but related intended-use provider population clinical validation study. 6 Optimizing the sensitivity of a diagnostic triage test necessarily comes at the expense of a reduced level of specificity or low positive predictive value (PPV).…”

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confidence: 99%

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Impact of a multivariate index assay on referral patterns for surgical management of an adnexal mass

Bristow

Hodeib

Smith³

et al. 2013

American Journal of Obstetrics and Gynecology

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OBJECTIVE:To determine the impact on referral patterns of using a Multivariate Index Assay, CA125, modified-American College of Obstetricians and Gynecologists referral guidelines, and clinical assessment among patients undergoing surgery for an adnexal mass after initial evaluation by nongynecologic oncologists.STUDY DESIGN: Overall, 770 patients were enrolled by nongynecologic oncologists from 2 related, multiinstitutional, prospective trials and analyzed retrospectively. All patients had preoperative imaging and biomarker analysis. The subset of patients enrolled by nongynecologic oncologists was analyzed to determine the projected referral patterns and sensitivity for malignancy based on multivariate index assay (MIA), CA125, modified-American College of Obstetricians and Gynecologists (ACOG) guidelines, and clinical assessment compared with actual practice. RESULTS:The prevalence of malignancy was 21.3% (n ¼ 164 MIA demonstrated statistically significant higher sensitivity (P < .0001) and lower specificity (P < .0001) for detecting malignancy compared with clinical assessment, CA125, and modified-ACOG guidelines. CONCLUSION:In this study population, use of MIA as a risk stratification test was associated with referral patterns by nongynecologic oncologists comparable to actual clinical practice and higher sensitivity for malignancy than other adnexal mass triage algorithms.

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Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer

Berek

Friedlander

Bast

2017

Holland‐Frei Cancer Medicine

222

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Overview Ovarian cancer is one of the most treatable solid tumors, as the majority will respond temporarily to surgery and cytotoxic agents. The disease, however, frequently persists and recurs in 70% of cases, having the highest fatality‐to‐case ratio of all the gynecologic cancers. Ovarian cancer is neither a common nor a rare disease, with a lifetime risk of 1 in 70 and a prevalence in the postmenopausal population in the United States of 1 in 2500, which impact strategies for early detection and prevention. Germ line mutations of BRCA1 and BRCA2 are associated with 10–15% of ovarian cancers and increase the risk of ovarian cancer dramatically. Factors that contribute to persistent ovulation increase the risk in women with sporadic disease, whereas use of oral contraceptives decreases the risk of disease post menopause. While epithelial ovarian cancers have been thought to arise from the ovarian surface epithelium or in the lining of inclusion cysts beneath the ovarian surface, many high‐grade serous “ovarian” carcinomas as well as peritoneal cancers are now believed to arise in the fimbriae of fallopian tube, rather than the ovary or peritoneum. Epithelial ovarian cancers can exhibit serous, endometrioid, mucinous, or clear cell histotypes. Low‐grade type I ovarian cancers grow slowly, can evolve from tumors of low malignant potential, bear Ras mutations in a majority of cases, express wild type TP53, often are detected in early stage (I–II), and respond less frequently to platinum‐ and taxane‐based therapy. High‐grade type II ovarian cancers grow rapidly, arise from precursors with TP53 mutations, are driven by DNA copy number changes, are diagnosed in late stage (III–IV), and frequently respond to combination chemotherapy. Owing to a lack of specific symptoms or an effective screening strategy, more than 70% of ovarian cancers are diagnosed in an advanced stage (III–IV). Primary treatment of epithelial ovarian cancer involves cytoreductive surgery and 6–8 cycles of carboplatin and paclitaxel. For those women with small volumes of disease after surgery, intraperitoneal administration of chemotherapy improves survival. Recurrent disease cannot be cured with currently available agents, but survival can be prolonged with combinations of cytotoxic agents including retreatment with paclitaxel and carboplatin. Palliative agents include liposomal doxorubicin, gemcitabine, topotecan, bevacizumab, pemetrexed, and etoposide. Experimental therapy for low‐grade cancers involves MEK inhibitors, whereas trials of PI3K pathway inhibitors and PARP inhibitors are underway in patients with high‐grade epithelial ovarian cancers. Combinations of targeted agents will be required.

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Effectiveness of a Multivariate Index Assay in the Preoperative Assessment of Ovarian Tumors

Abstract: The multivariate index assay demonstrated higher sensitivity and lower specificity compared with physician assessment and CA 125 in detecting ovarian malignancies.

Cited by 214 publications

References 26 publications

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies

Impact of a multivariate index assay on referral patterns for surgical management of an adnexal mass

Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer

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