Clinical trial NCT02836275: Value of MRI in the Characterization of Ovarian Masses Unable to Classify With Ultrasound Using the International Ovarian Tumor Analysis (IOTA) Simple Rules
Official title: Characterization of Ovarian Masses Unable to Classify With Ultrasound Using the International Ovarian Tumor Analysis (IOTA) Simple Rules: Value of Pelvic MRI With Perfusion- and Diffusion-weighted Imaging
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Patients With a Sonographically Unclassifiable Adnexal Mass Using the IOTA Simple Rules
Keywords: Adnexal Diseases
Ovary
Ovarian Neoplasms
Ovarian Cysts
Ovarian Diseases
Ultrasonography
Ultrasonography, Doppler
Magnetic Resonance Imaging
Diffusion Magnetic Resonance Imaging
Diagnosis
Early Diagnosis
Early Detection of Cancer
Genital Neoplasms, Female
Genital Diseases, Female
Urogenital Neoplasms
Cysts
Endocrine System Diseases
Gonadal Disorders
Neoplasms
Endocrine Gland Neoplasms
International Ovarian Tumor Analysis
Simple Rules
Preoperative Evaluation
Perfusion -and Diffusion-weighted Imaging
Adnexal Masses
Ovarian Tumors
Lead sponsor: KU Leuven
Sponsor class: OTHER
First posted: 2016-07-19
Enrollment: 250
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Gynecological ultrasound is well known as the preferred exam to assess patients with ovarian tumors. The International Ovarian Tumor Analysis (IOTA) group developed the 'Simple Rules' to classify an ovarian tumor as benign or malignant. In about 1/5 of patients the Simple Rules give an inconclusive result and therefore a suitable second line test is necessary. Recently the ADNEXMR SCORING system was developed, this is the first Magnetic Resonance Imaging (MRI) score system that focuses on ovarian tumors.

The aim of this prospective study is to evaluate the performance of pelvic MRI examination with perfusion -and diffusion- weighted sequences and the application of the ADNEXMR SCORING system in ovarian tumors that cannot be classified by the IOTA Simple Rules (regarding the prediction of malignancy). Other aims are the determination of the malignancy rate per ADNEXMR SCORING system class, the evaluation of interobserver reproducibility and the assessment of the accuracy of the specific diagnosis based on MRI images.

The study is a multicenter prospective study. In centers where perfusion -and diffusion weighted MRI imaging is not a part of clinical routine in unclassifiable ovarian masses based on ultrasound, the study is considered to be interventional. However, in other centres, depending on the local guidelines, perfusion -and diffusion weighted MRI imaging can be standard of care. In these centres, the study can be considered to be observational.

The IOTA-MRI project is linked to the IOTA study. In this multicenter study different diagnostic ultrasound algorithms are tested prospectively in patients with an ovarian mass prior to surgery. This study allows to define a subgroup of patients in which Simple Rules are inconclusive, in other words the population eligible for inclusion in the IOTA-MRI project. We plan to include 250 patients in the IOTA-MRI study. Patients will be included consecutively, yet only after completing the informed consent. Recruitment will take 2 years of time as of the start of the individual center.

The gold standard is the histopathology diagnosis of the mass within 120 days after ultrasound evaluation. The surgical approach is chosen by the managing clinician.

Detailed description: Ovarian cancer is a common and lethal disease for which early detection and treatment in high volume centers and by specialized clinicians is known to improve survival. Hence, accurate methods to preoperatively characterize the nature of an ovarian tumor are pivotal. The IOTA group has suggested Simple ultrasound based rules that can be used to classify adnexal masses as benign or malignant. In about 1/5 of patients the Simple Rules give an inconclusive result and therefore a suitable second line test is necessary. The benefit of using MRI in sonographically indeterminate masses has been evaluated previously. However, the ability of MRI to correctly classify tumors unclassifiable by the IOTA Simple Rules has not been examined. The group of Thomassin-Naggara et al has recently developed the ADNEXMR SCORING system, this is the first Magnetic Resonance Imaging (MRI) score system that focuses on ovarian tumors.

The primary aim of this prospective study is to evaluate the performance of pelvic MRI examination with perfusion -and diffusion- weighted sequences and the application of the ADNEXMR SCORING system in ovarian tumors that cannot be classified by the IOTA Simple Rules (regarding the prediction of malignancy). Secondary aims are the determination of the malignancy rate per ADNEXMR SCORING system class, the evaluation of interobserver reproducibility and the assessment of the accuracy of the specific diagnosis based on MRI images.

The study is a multicenter prospective study. In centers where perfusion -and diffusion weighted MRI imaging is not a part of clinical routine in unclassifiable ovarian masses based on ultrasound, the study is considered to be interventional. However, in other centres, depending on the local guidelines, perfusion -and diffusion weighted MRI imaging can be standard of care. In these centres, the study can be considered to be observational.

The IOTA-MRI project is linked to the IOTA study. In this multicenter study different diagnostic ultrasound algorithms are tested prospectively in patients with an ovarian mass prior to surgery. This study allows to define a subgroup of patients in which Simple Rules are inconclusive, in other words the population eligible for inclusion in the IOTA-MRI project. We plan to include 250 patients in the IOTA-MRI study. Patients will be included consecutively, yet only after completing the informed consent. Recruitment will take 2 years of time as of the start of the individual center.

At first, a standardized patient history will be registered, followed by a standardized transvaginal gynecological ultrasound. All variables required for the diagnostic models as well as the subjective diagnosis and certainty of diagnosis by the examiner will be collected. Quality control is provided by the fact that all examiners involved in gynecological ultrasound have completed IOTA-training and succeeded in a certification test. All data will be registered in an online Clinical Data Miner system (CDM).

In case that the results of the Simple Rules are inconclusive, and surgery is justifiable, the patient will be informed about the IOTA-MRI study. If the patient agrees to participate, the inclusion criteria are met and if there are no contra-indications, the patient will be referred to the radiology department of the same center or an affiliated center.

Second, at the radiology department, a standardized pelvic MRI examination will take place (diffusion- and perfusion- weighted sequences). All the variables that are needed for the classification of the ADNEXMR SCORING system as well as the subjective diagnosis of the radiologist, will be registered in CDM. Quality control in this part is provided by the fact that all radiologists involved in the study are certified by EURAD (EURopean ADnex mr score).

The gold standard is the histopathology diagnosis of the mass within 120 days after ultrasound evaluation. The surgical approach is chosen by the managing clinician. In case of malignancy, staging of the tumor will be reported by the International Federation of Gynecology and Obstetrics (FIGO) classification. All results will be registered in CDM.

Eligibility criteria: Inclusion Criteria:

* Any adult woman with an adnexal mass unclassified by gynecological ultrasound using the IOTA Simple Rules.
* Patient planned for surgery.

Exclusion Criteria:

* Any lesion with conclusive result on gynecological ultrasound using the IOTA Simple Rules.
* Cysts that are deemed to be clearly physiological and less than 3 cm in maximum diameter are not eligible for inclusion.
* No surgery performed or surgery performed \>120 days after ultrasound scan.
* Denial or withdrawal of informed consent.
* Contra-indication for MRI
* Current pregnancy
* Age \< 18 years

Primary outcomes:
measure: The sensitivity and specificity of the ADNEXMR SCORING system in classifying adnexal masses as malignant or benign using MRI with diffusion- and perfusion-weighted sequences in masses unclassified by the IOTA Simple Rules.
timeFrame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 120 days after ultrasound examination.
Secondary outcomes:
measure: Proportion of malignant masses per level of the ADNEXMR SCORING system.
timeFrame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 120 days after ultrasound examination.
measure: Interobserver reproducibility of ADNEXMR SCORING system using MRI with diffusion- and perfusion-weighted sequences by comparing lesion characterization (interpretation) and region of interest delineation on the perfusion curve.
timeFrame: During estimated recruitment period of 2 years.
measure: Accuracy of the suggested specific diagnosis made on the basis of the MRI images.
timeFrame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 120 days after ultrasound examination.
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
Study officials:
affiliation: Department of Radiology, Hôpital Tenon, Paris, FRANCE
name: Isabelle Thomassin-Naggara, MD, PhD
role: STUDY_CHAIR
affiliation: Imperial College London, London, UNITED KINGDOM
name: Andrea Rockall, MBBS, MRCP, FRCR
role: STUDY_CHAIR
affiliation: Queen Charlotte's & Chelsea Hospital, Imperial College London, London, UNITED KINGDOM
name: Tom Bourne, MD, PhD
role: STUDY_CHAIR
affiliation: Department Development & Regeneration, KU Leuven, Leuven, BELGIUM
name: Ben Van Calster, MSc, PhD
role: STUDY_CHAIR
affiliation: Department of Obstetrics and Gynecology, University Hospitals KU Leuven, Leuven, BELGIUM
name: Ignace Vergote, MD, PhD
role: STUDY_CHAIR
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