LR2 risk model to diagnose ovarian cancer
We are writing to you to explain why the web applications of ADNEX and of LR1, LR2 and SRRisk are no longer available on the IOTA website, and why the ADNEX app and the other IOTA apps are no longer available in app-store or Google play. The explanation is a change in the European Medical Device Regulation (MDR), a set of regulations that governs the sale and distribution of medical devices within the European Union (EU).
According to the new MDR, the ADNEX calculator and the other IOTA calculators (web-application, app for apple and android devices and any other applications of the IOTA calculators) are now classified as medical devices. As a result, these calculators must undergo a certification process before they can be legally made available to healthcare professionals. Therefore, we have suspended the availability of the ADNEX calculator and the other calculators on our website until we have received the required certification, and we have also removed them from app-store and google play.
The process of obtaining MDR certification for medical devices is complex, very expensive and time-consuming. The IOTA steering committee is now working hard to obtain certification of the ADNEX web application, but we cannot provide reliable information on how long this process may take.
Please, observe that it is not the ADNEX model itself that is questioned and needs "certification". The ADNEX model has been externally validated on thousands of patients in different countries and settings and has been shown to have excellent ability to discriminate between benign and maligant adenxal masses. It is the calculator itself (web-application or app for android and apple devises) that needs to obtain certification.
An ADNEX app and some of the other IOTA risk calculation apps are available in many ultrasound systems. The apps in ultrasound systems have the necessary certification according to the manufacturers of the ultrasound machines. If you do not have an ultrasound machine with the ADNEX app or any of the other IOTA apps, we suggest you use the IOTA Benign descriptors or the IOTA Simple Rules.
We are very sorry about the situation. We know it causes substantial inconvenience.
If you have any questions or concerns, please contact us. We will keep you informed about any updates regarding the availability of the IOTA calculators.
Thank you for your understanding and continued support.
The IOTA Steering Committee:
Ben van Calster
The LR2 risk model can be used by medical doctors to preoperatively diagnose ovarian cancer in women who have at least one persistent adnexal (ovarian, para-ovarian, and tubal) tumor and are considered to require surgery.1 LR2 estimates the probability that an adnexal tumor is malignant. LR2 was developed by clinicians and statisticians from the International Ovarian Tumor Analysis (IOTA) group, based on clinical and ultrasound data from 754 women recruited at 9 centers in 5 countries (Italy, Belgium, Sweden, France, and UK). All patients included required surgery as judged by a local clinician. All current diagnostic models for adnexal tumors (e.g. IOTA models, RMI, ROMA) have been created for patients undergoing surgery, i.e. patients selected for expectant management were excluded when creating the model.
LR2 uses six predictors. There is one clinical variable, age, and five ultrasound variables, maximal diameter of the largest solid component, irregular internal cyst walls, presence of papillary projections with detectable flow, acoustic shadows, and ascites. All patients included required surgery as judged by a local clinician. As with all current diagnostic models for adnexal tumours (e.g. IOTA models, RMI, ROMA) it implies that patients selected for expectant management were excluded when creating the model. As a consequence LR2 cannot be applied to conservatively treated adnexal tumors.
The manuscript describing the model is published in the Journal of Clinical Oncology.1 The model has been externally validated in several subsequent studies.2-10 These studies confirm the discrimination between benign and malignant masses. However, calibration results suggest that LR2 underestimates the risk of malignancy. The discrimination performance of LR2 has been included in two systematic reviews on the subject.11-12
LR2 cannot replace training and experience in ultrasonography and cannot compensate for poor quality ultrasound equipment. The parameters used in LR2 are based on the terms and definitions as published by the IOTA group.13
- Timmerman D, et al. J Clin Oncol 2005;23:8794-801.
- Van Holsbeke C, et al. Clin Cancer Res 2009;15:684-91.
- Timmerman D, et al. Ultrasound Obstet Gynecol 2010;36:226-34.
- Van Holsbeke C, Van Calster B, et al. Clin Cancer Res 2012;18:815-25. [same data as ref 3]
- Nunes N, et al. Ultrasound Obstet Gynecol 2012;40:355-9.
- Sayasneh A, et al. Br J Cancer 2013;108:2448-54.
- Kaijser J, et al. Gynecol Oncol 2013;129:377-83.
- Nunes N, et al. Int J Gynecol Cancer 2013;23:1583-9.
- Testa A, Kaijser J, et al. Br J Cancer 2014;111:680-8.
- Meys EM, et al. Ultrasound Obstet Gynecol 2016 [Epub ahead of print].
- Kaijser J, et al. Hum Reprod Update 2014;20:449-62.
- Meys EM, et al. Eur J Cancer 2016;58:17-29.
- Timmerman D, et al. Ultrasound Obstet Gynecol 2000;16:500-505