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  3. Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study
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Research

Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5920 (Published 15 October 2014) Cite this as: BMJ 2014;349:g5920
  1. Ben Van Calster, professor1,
  2. Kirsten Van Hoorde, doctoral researcher23,
  3. Lil Valentin, professor4,
  4. Antonia C Testa, professor5,
  5. Daniela Fischerova, consultant gynaecologist6,
  6. Caroline Van Holsbeke, consultant gynaecologist7,
  7. Luca Savelli, consultant gynaecologist8,
  8. Dorella Franchi, consultant gynaecologist9,
  9. Elisabeth Epstein, professor10,
  10. Jeroen Kaijser, research fellow111,
  11. Vanya Van Belle, postdoctoral researcher23,
  12. Artur Czekierdowski, professor12,
  13. Stefano Guerriero, professor13,
  14. Robert Fruscio, consultant gynaecologist14,
  15. Chiara Lanzani, consultant gynaecologist15,
  16. Felice Scala, consultant gynaecologist16,
  17. Tom Bourne, professor11117,
  18. Dirk Timmerman, professor111
  19. International Ovarian Tumour Analysis (IOTA) group
  1. 1Department of Development and Regeneration, KU Leuven, Herestraat 49 box 7003, 3000 Leuven, Belgium
  2. 2Department of Electrical Engineering, KU Leuven, Leuven, Belgium
  3. 3iMinds Medical Information Technologies, KU Leuven, Leuven, Belgium
  4. 4Department of Obstetrics and Gynaecology, Skåne University Hospital Malmö, Lund University, Malmö, Sweden
  5. 5Department of Oncology, Catholic University of the Sacred Heart, Rome, Italy
  6. 6Gynaecological Oncology Center, Department of Obstetrics and Gynaecology, Charles University, Prague, Czech Republic
  7. 7Department of Obstetrics and Gynaecology, Ziekenhuis Oost Limburg, Genk, Belgium
  8. 8Gynaecology and Reproductive Medicine Unit, S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
  9. 9Preventive Gynaecology Unit, Division of Gynaecology, European Institute of Oncology, Milan, Italy
  10. 10Department of Obstetrics and Gynaecology, Karolinska University Hospital, Stockholm, Sweden
  11. 11Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium
  12. 121st Department of Gynaecological Oncology and Gynaecology, Medical University in Lublin, Lublin, Poland
  13. 13Department of Obstetrics and Gynaecology, Azienda Ospedaliero Universitaria di Cagliari, Cagliari, Italy
  14. 14Clinic of Obstetrics and Gynaecology, University of Milan-Bicocca, San Gerardo Hospital, Monza, Italy
  15. 15Department of Woman, Mother and Neonate, Buzzi Children’s Hospital, Biological and Clinical School of Medicine, University of Milan, Milan, Italy
  16. 16Department of Gynaecologic Oncology, Istituto Nazionale Tumori, Naples, Italy
  17. 17Queen Charlotte’s and Chelsea Hospital, Imperial College, London, UK
  1. Correspondence to: B Van Calster ben.vancalster{at}med.kuleuven.be
  • Accepted 5 September 2014

Abstract

Objectives To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.

Design Observational diagnostic study using prospectively collected clinical and ultrasound data.

Setting 24 ultrasound centres in 10 countries.

Participants Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients.

Main outcome measures Histological classification and surgical staging of the mass.

Results The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate.

Conclusions The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Footnotes

  • Contributors: BVC conceived and designed the study, with additional support from KVH, LV, TB, and DT. LV, ACT, DFi, CVH, LS, DFr, EE, JK, AC, SG, RF, CL, FS, and DT enrolled patients and acquired data. BVC, KVH, CVH, JK, and DT were involved in data cleaning. BVC analysed the data, with support from KVH and VVB. BVC, KVH, LV, ACT, JK, VVB, TB, and DT were involved in data interpretation. BVC, JK, TB, and DT wrote the first draft of the manuscript, which was then critically reviewed and revised by the other coauthors. All authors approved the final version of the manuscript for submission. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. BVC, LV, TB, and DT are the guarantors

  • Funding: This study was supported by the Flemish government: Research Foundation–Flanders (FWO) project G049312N, Flanders’ Agency for Innovation by Science and Technology (IWT) project IWT-TBM 070706-IOTA3, and iMinds 2013. BVC and VVB are postdoctoral fellows of FWO. KVH is a doctoral fellow of IWT. TB is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, NIHR or Department of Health. LV is supported by the Swedish Medical Research Council (grants K2001-72X-11605-06A, K2002-72X-11605-07B, K2004-73X-11605-09A, and K2006-73X-11605-11-3), funds administered by Malmö University Hospital and Skåne University Hospital, Allmänna Sjukhusets i Malmö Stiftelse för bekämpande av cancer (the Malmö General Hospital Foundation for fighting against cancer), and two Swedish governmental grants (ALF-medel and Landstingsfinansierad Regional Forskning). The sponsors had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the work for publication. The researchers performed this work independently of the funding sources.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The research protocols were approved by the ethics committee of the University Hospitals KU Leuven and by each centre’s local ethics committee.

  • Data sharing: No additional data available.

  • Transparency: The manuscripts’ guarantors (BVC, LV, TB, and DT) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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