Patients With Adnexal Mass Prior to SurgeryIOTA7NCT02847832
Prospective Validation and Comparison of Different Ultrasound Methods for Discrimination Between Benign and Malignant Ovarian/Tubal Masses Prior to Surgery
An observational study of Patients With Adnexal Mass Prior to Surgery, run by KU Leuven at 1 site in Belgium.
Trial summary
The ability of different methods to discriminate between benign and malignant adnexal masses has been compared in a meta-analysis showing that the IOTA Simple Rules and the IOTA logistic regression model LR2 were superior to RMI and to all other methods for predicting malignancy in an adnexal mass included in the… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Patients With Adnexal Mass Prior to Surgery
- What is being tested?
- Standardized transvaginal ultrasound examination
- How many people
- 1,700 participants
- Where
- 1 siteBelgium
- Study dates
- Oct 2016to Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Study population: Consecutive patients with a known or suspected adnexal mass examined with transvaginal (or transrectal if vaginal is not possible) ultrasound by an IOTA certified ultrasound examiner and confirmed to have an adnexal mass judged not to be physiological but likely to undergo surgery (primarily planned for surgical management based on subjective assessment by the ultrasound investigator). Different types of ultrasound centers (general gynecologic outpatient clinic or specialized ultrasound centers) and examiners with different levels of ultrasound experience will be involved.
Who may be able to join
- Any woman presenting with an adnexal mass judged not to be physiological and likely to undergo surgery (primarily planned for surgical management based on subjective assessment by the ultrasound examiner; however, the ultrasound examiner is allowed to change the advised management to conservative management after the results of Simple Rules or ADNEX are known).
- Pregnant patients can be included but will be analysed separately.
- Patients finally selected for conservative management can be included but will not be used for all statistical analyses.
- For patients selected for surgery, delay of surgery is not an exclusion criterion for this study, but for selected objectives only those patients in whom surgery was performed within 180 days after the ultrasound examination will be assessed.
- Patients can be selected at any age, but for patients <18 years old, a guardian's permission should be obtained.
- Patients that only underwent transabdominal scanning can be included in the study, but will be analysed separately.
Who cannot join
- Previous bilateral adnexectomy
- Denial or withdrawal of informed consent
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
University Hospitals Leuven
Leuven, 3000
Dirk Timmerman, PhD
About this study
Official title: Prospective Validation and Comparison of Subjective Assessment, the International Ovarian Tumor Analysis (IOTA) ADNEX Model, Logistic Regression Model LR2, Simple Rules and the Risk of Malignancy Index (RMI) for Discrimination Between Benign and Malignant Adnexal Masses in the Hands of Ultrasound Examiners With Different Levels of Experience
The ability of different methods to discriminate between benign and malignant adnexal masses has been compared in a meta-analysis showing that the IOTA Simple Rules and the IOTA logistic regression model LR2 were superior to RMI and to all other methods for predicting malignancy in an adnexal mass included in the meta-analysis. However, a fair comparison of methods requires them to be applied on the same tumor population.
The general objective of this study is to prospectively validate the Simple Rules, ADNEX, the Simple Rules risk model, LR2, and RMI on a large multicenter dataset to allow direct comparison of these tools.
IOTA7 is an international multicenter prospective observational study including different types of ultrasound centers and examiners with different levels of ultrasound experience. In total, about 1700 adnexal masses with histological outcome will be included in IOTA 7.
Read the 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 best ultrasound method for discrimination between benign and malignant adnexal masses is subjective assessment, i.e. subjective evaluation of ultrasound findings. Subjective assessment, however, requires a very experienced ultrasound examiner. More objective methods may be preferred by less experienced examiners who are not confident with using subjective assessment. The Risk of Malignancy Index (RMI) is one such method. There are also more recently developed methods. The International Ovarian Tumor Analysis (IOTA) group have created logistic regression models (LR1, LR2, and the ADNEX model) including clinical and ultrasound information to calculate the likelihood of malignancy in adnexal masses.
The IOTA group has also suggested simple ultrasound rules that can be used to classify adnexal masses as benign or malignant.
The ability of different methods to discriminate between benign and malignant adnexal masses has been compared in a meta-analysis showing that the IOTA Simple Rules and the IOTA logistic regression model LR2 were superior to RMI and to all other methods for predicting malignancy in an adnexal mass included in the meta-analysis. However, a fair comparison of methods requires them to be applied on the same tumor population.
The general objective of this study is to prospectively validate the Simple Rules, ADNEX, the Simple Rules risk model, LR2, and RMI on a large multicenter dataset to allow direct comparison of these tools. The patients will be examined by operators of varying levels of experience, such that the investigators can study how experience might affect diagnostic performance.
IOTA7 is an international multicenter prospective observational study including different types of ultrasound centers and examiners with different levels of ultrasound experience. In total, about 1700 adnexal masses with histological outcome will be included in IOTA 7.
Patients with a known or suspected adnexal mass examined with transvaginal (or transrectal if vaginal is not possible) ultrasound by an IOTA certified ultrasound examiner and confirmed to have an adnexal mass judged not to be physiological but likely to undergo surgery (primarily planned for surgical management based on subjective assessment by the ultrasound investigator) will be recruited consecutively Upon inclusion in the study, an oral or written (depending on the requirements of the local Ethics Committee) informed consent is obtained from the patient.
Data collection is done through the web-based clinical data miner (CDM) software. Data are stored on a secure server.
First, clinical information about the patient is entered into CDM. Second, the ultrasound examiner provides a diagnosis based on subjective assessment, and notes the suggested management. Third, detailed ultrasound information needed for the different models to be validated is entered. When these data have been frozen (so they can no longer be changed) the examiner gets access to the results of the Simple Rules and ADNEX. The ultrasound examiner then records whether these results make him/her change the management suggested on the basis of subjective assessment. If so the new management is specified.
Gold standard for validation of discriminative ability and calibration is the histology of the adnexal mass within 180 days after the ultrasound examination following surgical removal by laparotomy or laparoscopy as considered appropriate by the surgeon. In case of malignancy, the stage of the malignant tumors using the classification of the International Federation of Gynecology and Obstetrics (FIGO) is noted.
- Being tested
- Standardized transvaginal ultrasound examination
- Keywords
- Adnexal Diseases, Ovary, Ovarian Neoplasms, Ovarian Cysts, Ovarian Diseases, Ultrasonography, Ultrasonography, Doppler, 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
- Medical subject headings
- Adnexal Diseases, Ovarian Neoplasms, Ovarian Cysts, Ovarian Diseases, Disease, Genital Neoplasms, Female, Genital Diseases, Female, Urogenital Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standardized transvaginal ultrasound examinationOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity, specificity, positive and negative likelihood ratios with regard to detection of malignancy for different ultrasound methods
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUCs for discrimination between benign and malignant masses for prediction models.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Secondary outcomes (12)
Flexible calibration curves based on local regression (loess) to assess calibration of the estimated risks on malignancy given by the risk prediction models.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Sensitivity, specificity, positive and negative likelihood ratios with regard to detection of malignancy for different ultrasound methods, in hands of examiners with different level of experience.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUCs for prediction models, in hands of examiners with different level of experience.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Sensitivity, specificity, positive and negative likelihood ratios with regard to detection of malignancy for different ultrasound methods, where the Simple Rules are inconclusive.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUCs for prediction models, where the Simple Rules are inconclusive.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Change of the suggested management based on subjective assessment depending on the level of expertise of the ultrasound examiner, after results of the Simple Rules have been shown.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Polytomous discrimination index for the ADNEX model to discriminate between different classes of histology.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUCs for each pair of outcome categories using the conditional risk method for the ADNEX model to discriminate between different classes of histology.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Multinomial calibration curves for the ADNEX model to predict benign tumors, borderline tumors, stage 1 primary ovarian cancer, stage 2-4 primary ovarian cancer and metastatic cancer.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Adjusted odds ratios with regard to malignancy for selected ultrasound characteristics, mainly papillation characteristics, in the subgroup of unilocular cysts with papillations.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Sensitivity and specificity with regard to malignancy at different risk cutoffs, for a risk prediction model in unilocular cysts with papillations based on a limited number of variables selected a priori.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUC for a risk prediction model in unilocular cysts with papillations based on a limited number of variables selected a priori.
Measured: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2016 (estimated)
- Study startOct 2016
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Patients With Adnexal Mass Prior to SurgeryStudies of the same condition, open and under way.
- More trials run by KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dirk Timmerman, KU Leuven
- Investigators
- Tom Bourne, MD, PhD, Study chair, Queen Charlotte's & Chelsea Hospital, Imperial College London, London, UNITED KINGDOMBen Van Calster, MSc, PhD, Study chair, Department Development & Regeneration, KU Leuven, Leuven, BELGIUMIgnace Vergote, MD, PhD, Study chair, Department of Obstetrics and Gynecology, University Hospitals KU Leuven, Leuven, BELGIUMLil Valentin, MD, PhD, Study chair, Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, SWEDENAntonia C Testa, MD, PhD, Study chair, Unità Operativa di Ginecologia Oncologica Dipartimento Tutela della Salute della Donna e della Vita Nascente, Università Cattolica di Sacro Cuore, Roma, ITALYSabine Van Huffel, MSc, PhD, Study chair, Department of electrical engineering (ESAT SCD-SISTA), KU Leuven, Heverlee-Leuven, BELGIUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02847832
- Sponsor's protocol ID
- IOTA7 s59207
- Acronym
- IOTA7
- Status last verified
- Apr 2020
- First submitted
- 15 Jul 2016
- Last updated
- 14 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Woo YL, Kyrgiou M, Bryant A, Everett T, Dickinson HO. Centralisation of services for gynaecological cancers - a Cochrane systematic review. Gynecol Oncol. 2012 Aug;126(2):286-90. doi: 10.1016/j.ygyno.2012.04.012. Epub 2012 Apr 13.
PubMed 22507534Engelen MJ, Kos HE, Willemse PH, Aalders JG, de Vries EG, Schaapveld M, Otter R, van der Zee AG. Surgery by consultant gynecologic oncologists improves survival in patients with ovarian carcinoma. Cancer. 2006 Feb 1;106(3):589-98. doi: 10.1002/cncr.21616.
PubMed 16369985Earle CC, Schrag D, Neville BA, Yabroff KR, Topor M, Fahey A, Trimble EL, Bodurka DC, Bristow RE, Carney M, Warren JL. Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients. J Natl Cancer Inst. 2006 Feb 1;98(3):172-80. doi: 10.1093/jnci/djj019.
PubMed 16449677Vernooij F, Heintz AP, Witteveen PO, van der Heiden-van der Loo M, Coebergh JW, van der Graaf Y. Specialized care and survival of ovarian cancer patients in The Netherlands: nationwide cohort study. J Natl Cancer Inst. 2008 Mar 19;100(6):399-406. doi: 10.1093/jnci/djn033. Epub 2008 Mar 11.
PubMed 18334710Valentin L, Hagen B, Tingulstad S, Eik-Nes S. Comparison of 'pattern recognition' and logistic regression models for discrimination between benign and malignant pelvic masses: a prospective cross validation. Ultrasound Obstet Gynecol. 2001 Oct;18(4):357-65. doi: 10.1046/j.0960-7692.2001.00500.x.
PubMed 11778996Timmerman D. The use of mathematical models to evaluate pelvic masses; can they beat an expert operator? Best Pract Res Clin Obstet Gynaecol. 2004 Feb;18(1):91-104. doi: 10.1016/j.bpobgyn.2003.09.009.
PubMed 15123060Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990 Oct;97(10):922-9. doi: 10.1111/j.1471-0528.1990.tb02448.x.
PubMed 2223684Kaijser J, Sayasneh A, Van Hoorde K, Ghaem-Maghami S, Bourne T, Timmerman D, Van Calster B. Presurgical diagnosis of adnexal tumours using mathematical models and scoring systems: a systematic review and meta-analysis. Hum Reprod Update. 2014 May-Jun;20(3):449-62. doi: 10.1093/humupd/dmt059. Epub 2013 Dec 9.
PubMed 24327552Timmerman D, Testa AC, Bourne T, Ferrazzi E, Ameye L, Konstantinovic ML, Van Calster B, Collins WP, Vergote I, Van Huffel S, Valentin L; International Ovarian Tumor Analysis Group. Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: a multicenter study by the International Ovarian Tumor Analysis Group. J Clin Oncol. 2005 Dec 1;23(34):8794-801. doi: 10.1200/JCO.2005.01.7632.
PubMed 16314639Van Calster B, Van Hoorde K, Valentin L, Testa AC, Fischerova D, Van Holsbeke C, Savelli L, Franchi D, Epstein E, Kaijser J, Van Belle V, Czekierdowski A, Guerriero S, Fruscio R, Lanzani C, Scala F, Bourne T, Timmerman D; International Ovarian Tumour Analysis Group. 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 Oct 15;349:g5920. doi: 10.1136/bmj.g5920.
PubMed 25320247Timmerman D, Testa AC, Bourne T, Ameye L, Jurkovic D, Van Holsbeke C, Paladini D, Van Calster B, Vergote I, Van Huffel S, Valentin L. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol. 2008 Jun;31(6):681-90. doi: 10.1002/uog.5365.
PubMed 18504770Timmerman D, Van Calster B, Testa A, Savelli L, Fischerova D, Froyman W, Wynants L, Van Holsbeke C, Epstein E, Franchi D, Kaijser J, Czekierdowski A, Guerriero S, Fruscio R, Leone FPG, Rossi A, Landolfo C, Vergote I, Bourne T, Valentin L. Predicting the risk of malignancy in adnexal masses based on the Simple Rules from the International Ovarian Tumor Analysis group. Am J Obstet Gynecol. 2016 Apr;214(4):424-437. doi: 10.1016/j.ajog.2016.01.007. Epub 2016 Jan 19.
PubMed 26800772Installe AJ, Van den Bosch T, De Moor B, Timmerman D. Clinical data miner: an electronic case report form system with integrated data preprocessing and machine-learning libraries supporting clinical diagnostic model research. JMIR Med Inform. 2014 Oct 20;2(2):e28. doi: 10.2196/medinform.3251.
PubMed 25600863Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006 Nov;95 Suppl 1:S161-92. doi: 10.1016/S0020-7292(06)60033-7. No abstract available.
PubMed 17161157Taliento C, Van Nieuwenhuysen E, Labie P, Van Rompuy AS, Timmerman D, Froyman W. Correlation between ultrasound and gross pathology examination of malignant ovarian tumors: a pictorial review for pattern recognition. Int J Gynecol Cancer. 2026 May;36(5):104618. doi: 10.1016/j.ijgc.2026.104618. Epub 2026 Feb 24.
PubMed 41865621
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Validation and Comparison of Subjective Assessment, the International Ovarian Tumor Analysis (IOTA) ADNEX Model, Logistic Regression Model LR2, Simple Rules and the Risk of Malignancy Index (RMI) for Discrimination Between Benign and Malignant Adnexal Masses in the Hands of Ultrasound Examiners With Different Levels of Experience
- ClinicalTrials.gov ID
- NCT02847832
- Acronym / sponsor ID
- IOTA7 / IOTA7 s59207
- Keywords
- Adnexal Diseases, Ovary, Ovarian Neoplasms, Ovarian Cysts, Ovarian Diseases, Ultrasonography, Ultrasonography, Doppler, Diagnosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,700 participants (estimated)
- Lead sponsor
- KU LeuvenUniversity, hospital or other
- Study start
- Oct 2016
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 28 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ability of different methods to discriminate between benign and malignant adnexal masses has been compared in a meta-analysis showing that the IOTA Simple Rules and the IOTA logistic regression model LR2 were superior to RMI and to all other methods for predicting malignancy in an adnexal mass included in the meta-analysis. However, a fair comparison of methods requires them to be applied on the same tumor population.
The general objective of this study is to prospectively validate the Simple Rules, ADNEX, the Simple Rules risk model, LR2, and RMI on a large multicenter dataset to allow direct comparison of these tools.
IOTA7 is an international multicenter prospective observational study including different types of ultrasound centers and examiners with different levels of ultrasound experience. In total, about 1700 adnexal masses with histological outcome will be included in IOTA 7.
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 best ultrasound method for discrimination between benign and malignant adnexal masses is subjective assessment, i.e. subjective evaluation of ultrasound findings. Subjective assessment, however, requires a very experienced ultrasound examiner. More objective methods may be preferred by less experienced examiners who are not confident with using subjective assessment. The Risk of Malignancy Index (RMI) is one such method. There are also more recently developed methods. The International Ovarian Tumor Analysis (IOTA) group have created logistic regression models (LR1, LR2, and the ADNEX model) including clinical and ultrasound information to calculate the likelihood of malignancy in adnexal masses.
The IOTA group has also suggested simple ultrasound rules that can be used to classify adnexal masses as benign or malignant.
The ability of different methods to discriminate between benign and malignant adnexal masses has been compared in a meta-analysis showing that the IOTA Simple Rules and the IOTA logistic regression model LR2 were superior to RMI and to all other methods for predicting malignancy in an adnexal mass included in the meta-analysis. However, a fair comparison of methods requires them to be applied on the same tumor population.
The general objective of this study is to prospectively validate the Simple Rules, ADNEX, the Simple Rules risk model, LR2, and RMI on a large multicenter dataset to allow direct comparison of these tools. The patients will be examined by operators of varying levels of experience, such that the investigators can study how experience might affect diagnostic performance.
IOTA7 is an international multicenter prospective observational study including different types of ultrasound centers and examiners with different levels of ultrasound experience. In total, about 1700 adnexal masses with histological outcome will be included in IOTA 7.
Patients with a known or suspected adnexal mass examined with transvaginal (or transrectal if vaginal is not possible) ultrasound by an IOTA certified ultrasound examiner and confirmed to have an adnexal mass judged not to be physiological but likely to undergo surgery (primarily planned for surgical management based on subjective assessment by the ultrasound investigator) will be recruited consecutively Upon inclusion in the study, an oral or written (depending on the requirements of the local Ethics Committee) informed consent is obtained from the patient.
Data collection is done through the web-based clinical data miner (CDM) software. Data are stored on a secure server.
First, clinical information about the patient is entered into CDM. Second, the ultrasound examiner provides a diagnosis based on subjective assessment, and notes the suggested management. Third, detailed ultrasound information needed for the different models to be validated is entered. When these data have been frozen (so they can no longer be changed) the examiner gets access to the results of the Simple Rules and ADNEX. The ultrasound examiner then records whether these results make him/her change the management suggested on the basis of subjective assessment. If so the new management is specified.
Gold standard for validation of discriminative ability and calibration is the histology of the adnexal mass within 180 days after the ultrasound examination following surgical removal by laparotomy or laparoscopy as considered appropriate by the surgeon. In case of malignancy, the stage of the malignant tumors using the classification of the International Federation of Gynecology and Obstetrics (FIGO) is noted.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Consecutive patients with a known or suspected adnexal mass examined with transvaginal (or transrectal if vaginal is not possible) ultrasound by an IOTA certified ultrasound examiner and confirmed to have an adnexal mass judged not to be physiological but likely to undergo surgery (primarily planned for surgical management based on subjective assessment by the ultrasound investigator). Different types of ultrasound centers (general gynecologic outpatient clinic or specialized ultrasound centers) and examiners with different levels of ultrasound experience will be involved.
Key inclusion criteria (6 listed)
- Any woman presenting with an adnexal mass judged not to be physiological and likely to undergo surgery (primarily planned for surgical management based on subjective assessment by the ultrasound examiner; however, the ultrasound examiner is allowed to change the advised management to conservative management after the results of Simple Rules or ADNEX are known).
- Pregnant patients can be included but will be analysed separately.
- Patients finally selected for conservative management can be included but will not be used for all statistical analyses.
- For patients selected for surgery, delay of surgery is not an exclusion criterion for this study, but for selected objectives only those patients in whom surgery was performed within 180 days after the ultrasound examination will be assessed.
- Patients can be selected at any age, but for patients <18 years old, a guardian's permission should be obtained.
Key exclusion criteria (2 listed)
- Previous bilateral adnexectomy
- Denial or withdrawal of informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standardized transvaginal ultrasound examination | Other | – |
Primary outcome
Sensitivity, specificity, positive and negative likelihood ratios with regard to detection of malignancy for different ultrasound methods
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUCs for discrimination between benign and malignant masses for prediction models.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
12 secondary outcomes
Flexible calibration curves based on local regression (loess) to assess calibration of the estimated risks on malignancy given by the risk prediction models.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Sensitivity, specificity, positive and negative likelihood ratios with regard to detection of malignancy for different ultrasound methods, in hands of examiners with different level of experience.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUCs for prediction models, in hands of examiners with different level of experience.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Sensitivity, specificity, positive and negative likelihood ratios with regard to detection of malignancy for different ultrasound methods, where the Simple Rules are inconclusive.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUCs for prediction models, where the Simple Rules are inconclusive.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Change of the suggested management based on subjective assessment depending on the level of expertise of the ultrasound examiner, after results of the Simple Rules have been shown.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Polytomous discrimination index for the ADNEX model to discriminate between different classes of histology.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUCs for each pair of outcome categories using the conditional risk method for the ADNEX model to discriminate between different classes of histology.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Multinomial calibration curves for the ADNEX model to predict benign tumors, borderline tumors, stage 1 primary ovarian cancer, stage 2-4 primary ovarian cancer and metastatic cancer.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Adjusted odds ratios with regard to malignancy for selected ultrasound characteristics, mainly papillation characteristics, in the subgroup of unilocular cysts with papillations.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Sensitivity and specificity with regard to malignancy at different risk cutoffs, for a risk prediction model in unilocular cysts with papillations based on a limited number of variables selected a priori.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
AUC for a risk prediction model in unilocular cysts with papillations based on a limited number of variables selected a priori.
Time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2020.
- Background: PubMed 22507534Woo YL, Kyrgiou M, Bryant A, Everett T, Dickinson HO. Centralisation of services for gynaecological cancers - a Cochrane systematic review. Gynecol Oncol. 2012 Aug;126(2):286-90. doi: 10.1016/j.ygyno.2012.04.012. Epub 2012 Apr 13.
- Background: PubMed 16369985Engelen MJ, Kos HE, Willemse PH, Aalders JG, de Vries EG, Schaapveld M, Otter R, van der Zee AG. Surgery by consultant gynecologic oncologists improves survival in patients with ovarian carcinoma. Cancer. 2006 Feb 1;106(3):589-98. doi: 10.1002/cncr.21616.
- Background: PubMed 16449677Earle CC, Schrag D, Neville BA, Yabroff KR, Topor M, Fahey A, Trimble EL, Bodurka DC, Bristow RE, Carney M, Warren JL. Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients. J Natl Cancer Inst. 2006 Feb 1;98(3):172-80. doi: 10.1093/jnci/djj019.
- Background: PubMed 18334710Vernooij F, Heintz AP, Witteveen PO, van der Heiden-van der Loo M, Coebergh JW, van der Graaf Y. Specialized care and survival of ovarian cancer patients in The Netherlands: nationwide cohort study. J Natl Cancer Inst. 2008 Mar 19;100(6):399-406. doi: 10.1093/jnci/djn033. Epub 2008 Mar 11.
- Background: PubMed 11778996Valentin L, Hagen B, Tingulstad S, Eik-Nes S. Comparison of 'pattern recognition' and logistic regression models for discrimination between benign and malignant pelvic masses: a prospective cross validation. Ultrasound Obstet Gynecol. 2001 Oct;18(4):357-65. doi: 10.1046/j.0960-7692.2001.00500.x.
- Background: PubMed 15123060Timmerman D. The use of mathematical models to evaluate pelvic masses; can they beat an expert operator? Best Pract Res Clin Obstet Gynaecol. 2004 Feb;18(1):91-104. doi: 10.1016/j.bpobgyn.2003.09.009.
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- Background: PubMed 24327552Kaijser J, Sayasneh A, Van Hoorde K, Ghaem-Maghami S, Bourne T, Timmerman D, Van Calster B. Presurgical diagnosis of adnexal tumours using mathematical models and scoring systems: a systematic review and meta-analysis. Hum Reprod Update. 2014 May-Jun;20(3):449-62. doi: 10.1093/humupd/dmt059. Epub 2013 Dec 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom Bourne, MD, PhD study chair
Queen Charlotte's & Chelsea Hospital, Imperial College London, London, UNITED KINGDOM
Ben Van Calster, MSc, PhD study chair
Department Development & Regeneration, KU Leuven, Leuven, BELGIUM
Ignace Vergote, MD, PhD study chair
Department of Obstetrics and Gynecology, University Hospitals KU Leuven, Leuven, BELGIUM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Patients With Adnexal Mass Prior to Surgery, run by KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dirk Timmerman, MD, PhD (+32 16 344201, dirk.timmerman@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity, specificity, positive and negative likelihood ratios with regard to detection of malignancy for different ultrasound methods (time frame: During estimated recruitment period of 2 years. Gold standard is histopathology diagnosis within 180 days after ultrasound examination.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02847832, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2020.