A new strategy for calculating the risk of ovarian malignancy algorithm (ROMA)

Tae-Dong Jeong; Eun-Jung Cho; Dae-Hyun Ko; Woochang Lee; Sail Chun; Hi Jeong Kwon; Ki-Sook Hong; Yong-Man Kim; Won-Ki Min

doi:10.1515/cclm-2016-0582

Article

A new strategy for calculating the risk of ovarian malignancy algorithm (ROMA)

Tae-Dong Jeong , Eun-Jung Cho , Dae-Hyun Ko , Woochang Lee , Sail Chun , Hi Jeong Kwon , Ki-Sook Hong , Yong-Man Kim and Won-Ki Min

Published/Copyright: January 20, 2017

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 8

Abstract

Background:

Reliable quantitative measurements of HE4 and CA125 levels are required to calculate the risk of ovarian malignancy algorithm (ROMA) value. We suggest a new reporting strategy for interpreting ROMA values based on analytical measurement range (AMR) and qualified-intervals of the HE4 and CA125 results.

Methods:

HE4 and CA125 assays from Abbott and Roche were used. The AMRs and the qualified-intervals were as follows: Architect HE4 assay, 20–1500 and 17.2–2637.8 pmol/L; Architect CA125 II assay, 1–1000 and 3.9–14,163.0 U/mL; Elecsys HE4 assay, 15–1500 and 28.8–3847 pmol/L; Elecsys CA125 II assay, 0.6–5000 and 6.5–5000 U/mL. These values were used to simulate the ROMA values.

Results:

Reporting algorithm for the ROMA value could be classified into three categories. (1) If quantitative HE4 and CA125 levels are reliable, the numerical ROMA value can be reported. (2) If HE4 value is <20 and <28.8 for Abbott and Roche in premenopausal woman, the ROMA value should be reported as “low risk” regardless of the CA125 result. In postmenopausal woman, however, it should be reported as “low risk” (CA125<203.0 and <165.8 for Abbott and Roche) or “undetermined” (vice-versa value). (3) If CA125 value is <3.9 and <6.5 for Abbott and Roche, it should be reported as “low risk” (premenopausal HE4<51.5 and <62.2, postmenopausal HE4<323.0 and <281.5 for Abbott and Roche) or “undetermined” (vice-versa value).

Conclusions:

New reporting strategy will provide more informative reporting of ROMA values in clinical practice.

Keywords: CA125; HE4; quantitative measurement; risk of ovarian malignancy algorithm

Corresponding author: Woochang Lee, MD, PhD, Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea, Phone: +82-2-3010-4506, Fax: +82-2-478-0884

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol 2009;112:40–6.10.1016/j.ygyno.2008.08.031Search in Google Scholar

2. Moore RG, Jabre-Raughley M, Brown AK, Robison KM, Miller MC, Allard WJ, et al. Comparison of a novel multiple marker assay vs the risk of malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. Am J Obstet Gynecol 2010;203:228 e1–6.10.1016/j.ajog.2010.03.043Search in Google Scholar

3. Bandiera E, Romani C, Specchia C, Zanotti L, Galli C, Ruggeri G, et al. Serum human epididymis protein 4 and risk for ovarian malignancy algorithm as new diagnostic and prognostic tools for epithelial ovarian cancer management. Cancer Epidemiol Biomarkers Prev 2011;20:2496–506.10.1158/1055-9965.EPI-11-0635Search in Google Scholar

4. Sandri MT, Bottari F, Franchi D, Boveri S, Candiani M, Ronzoni S, et al. Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: correlation with pathological outcome. Gynecol Oncol 2013;128:233–8.10.1016/j.ygyno.2012.11.026Search in Google Scholar

5. Ruggeri G, Bandiera E, Zanotti L, Belloli S, Ravaggi A, Romani C, et al. HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and a combination algorithm. Clin Chim Acta 2011;412:1447–53.10.1016/j.cca.2011.04.028Search in Google Scholar

6. Chen WT, Gao X, Han XD, Zheng H, Guo L, Lu RQ. HE4 as a serum biomarker for ROMA prediction and prognosis of epithelial ovarian cancer. Asian Pac J Can Prev 2014;15:101–5.10.7314/APJCP.2014.15.1.101Search in Google Scholar

7. Elecsys® HE4 and CA 125 II and their use in the risk assessment of epithelial ovarian cancer by ROMA (Risk of Ovarian Malignancy Algorithm). Available at: http://www.cobas.com/content/dam/cobas_com/pdf/product/Elecsys%20HE4%20Human%20Epididymal%20Protein%204/ROMA%20fact%20sheet.pdf. Accessed 14 July 2015.Search in Google Scholar

8. Anton C, Carvalho FM, Oliveira EI, Maciel GA, Baracat EC, Carvalho JP. A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses. Clinics 2012;67:437–41.10.6061/clinics/2012(05)06Search in Google Scholar

9. Plebani M. HE4 in gynecological cancers: report of a European investigators and experts meeting. Clin Chem Lab Med 2012;50:2127–36.10.1515/cclm-2012-0373Search in Google Scholar PubMed

10. Ferraro S, Braga F, Lanzoni M, Boracchi P, Biganzoli EM, Panteghini M. Serum human epididymis protein 4 vs carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review. J Clin Pathol 2013;66:273–81.10.1136/jclinpath-2012-201031Search in Google Scholar PubMed

11. US Department of Health and Human Services. Draft Guidance for Industry, Clinical Laboratories, and Staff: In Vitro Diagnostic Multivariate Index Assays. Available at: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071455.pdf. Accessed 14 July 2015.Search in Google Scholar

12. Zhang Z. An in vitro diagnostic multivariate index assay (IVDMIA) for ovarian cancer: harvesting the power of multiple biomarkers. Rev Obstet Gynecol 2012;5:35–41.Search in Google Scholar

13. Zhang Z, Chan DW. The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidemiol Biomarkers Prev 2010;19:2995–9.10.1158/1055-9965.EPI-10-0580Search in Google Scholar PubMed PubMed Central

14. Yip P, Chen TH, Seshaiah P, Stephen LL, Michael-Ballard KL, Mapes JP, et al. Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers. PLoS One 2011;6:e29533.10.1371/journal.pone.0029533Search in Google Scholar PubMed PubMed Central

15. CAP’s Technology Assessment Committee. In vitro diagnostic multivariate assays (IVDMIAs). Available at: http://www.cap.org/apps/docs/committees/technology/ivdmia.pdf. Accessed 14 July 2015.Search in Google Scholar

Received: 2016-7-1

Accepted: 2016-12-5

Published Online: 2017-1-20

Published in Print: 2017-7-26

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Articles in the same Issue

https://doi.org/10.1515/cclm-2016-0582

Keywords for this article

CA125; HE4; quantitative measurement; risk of ovarian malignancy algorithm