pIOTA: Prospective Validation of the ADNEX Model for Discrimination Between Benign and Malignant Adnexal Masses in Pregnancy: International Ovarian Tumour Analysis in Pregnancy Study (p-IOTA)

Sponsor

Universitaire Ziekenhuizen KU Leuven (Other)

Overall Status

Recruiting

CT.gov ID

NCT05974618

Collaborator

(none)

1,000

Enrollment

Location

36.9

Anticipated Duration (Months)

27.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Prospective Validation of the ADNEX Model for discrimination between benign and malignant adnexal masses in pregnancy:

International Ovarian Tumour Analysis in pregnancy study (p-IOTA)

Condition or Disease	Intervention/Treatment	Phase
Adnexal Mass Adnexal Tumor Adnexal Cyst Pregnancy Related	Diagnostic Test: Ultrasound

Detailed Description

STUDY SUMMARY

TITLE Prospective Validation of the ADNEX Model for discrimination between benign and malignant adnexal masses in pregnancy: the International Ovarian Tumour Analysis in pregnancy study (p-IOTA).

DESIGN Multicentre, prospective cohort observational study.

BACKGROUND Adnexal masses are a common incidental finding in pregnancy. Whilst the majority are benign and resolve spontaneously, a proportion can exhibit suspicious features during pregnancy raising concern about an underlying malignancy. Correct classification of adnexal masses is particularly important during pregnancy given the potential foetal and maternal risks associated with surgical intervention. International Ovarian Tumour Analysis (IOTA) group have developed robust, ultrasound-based tools, including the ADNEX model to support the classification of adnexal masses. Ultrasound-based tools such the Modified Benign Simple Descriptors and ADNEX have been externally validated to aid in the classification of adnexal masses in non-pregnant women, but their use as a robust diagnostic tool in pregnancy remains to be demonstrated.

AIMS The principal objective of this study is to prospectively investigate the ability of the ADNEX Model and a 2-step strategy (i.e. Modified Benign Simple Descriptors followed by ADNEX) to correctly discriminate between benign and malignant adnexal masses diagnosed in pregnancy.

PRIMARY OUTCOME MEASURE False discovery rate (number of benign masses / number of masses classified as malignant) when using the ADNEX Model to discriminate between benign and malignant adnexal masses at 11-14 gestational weeks in pregnancy.

ELIGIBILITY All women 18 years old and above with an adnexal mass found on ultrasound scan during pregnancy - irrespective of whether the mass known before pregnancy OR diagnosed for the first time on ultrasound scan during pregnancy.

DURATION This study will be conducted over a minimum period of three years.

KEYWORDS IOTA, ovarian mass, benign, malignant, ultrasound, pregnancy, post-partum

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Prospective Validation of the ADNEX Model for Discrimination Between Benign and Malignant Adnexal Masses in Pregnancy: the International Ovarian Tumour Analysis in Pregnancy Study (p-IOTA).

Actual Study Start Date :

Jun 5, 2023

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
First arm (primary objective): First arm (primary objective): Adnexal mass scanned at 11-14 weeks. If the decision is to manage the adnexal mass conservatively, the patient is to be re-scanned once more: 0 - 90 days postpartum. In addition, the patient will be asked to enter into the third arm of the study (see below) knowing that she can opt out from that arm at any point. If she consents to participate in the third arm, she will participate in a series of longitudinal examinations as described for the third arm. All patients with a mass detected before 11 weeks will also be scanned at 11-14 weeks and can enter all three arms of the study. In this scenario, if more than one scan is performed during pregnancy before 11 weeks, only the first of several scans before 11 weeks will be included for the second and third arms of the study.	Diagnostic Test: Ultrasound A standardised transvaginal (supplemented with transabdominal if transvaginal is not sufficient) examination is performed. When a colour Doppler ultrasound examination is performed, the pulse repetition frequency should be 0.3-0.6 KHz. The colour Doppler gain should be increased until colour Doppler artefacts appear and then lowered until just below the reappearance of colour Doppler artefacts. Ultrasound frequency and "priority" (grey scale or colour/Power Doppler) must also be optimised when using colour/power Doppler. Doppler ultrasound should be used with all masses included, irrespective of gestational age.
Second arm (secondary objective): Second arm (secondary objective): Adnexal mass is seen for the first time during that pregnancy at any gestation. If the decision is to manage the adnexal mass conservatively, the patient is to be re-scanned once more: 0 - 90 days postpartum. For patients with a mass detected before 11 weeks, see also above (they will be re-scanned at both 11-14 weeks and at 0-90 days postpartum). In addition, the patient will be asked to enter into the third arm of the study knowing that she can opt out from that arm at any point. If she consents to this, she will participate in a series of longitudinal examinations as described for the third arm.	Diagnostic Test: Ultrasound A standardised transvaginal (supplemented with transabdominal if transvaginal is not sufficient) examination is performed. When a colour Doppler ultrasound examination is performed, the pulse repetition frequency should be 0.3-0.6 KHz. The colour Doppler gain should be increased until colour Doppler artefacts appear and then lowered until just below the reappearance of colour Doppler artefacts. Ultrasound frequency and "priority" (grey scale or colour/Power Doppler) must also be optimised when using colour/power Doppler. Doppler ultrasound should be used with all masses included, irrespective of gestational age.
Third arm (secondary objective): Third arm (secondary objective): Patients from the first and second arms who agree to enrol into the third arm i.e. longitudinal examination of an adnexal mass during pregnancy. For the purposes of the longitudinal evaluation, the time points for the ultrasound examination are: initial presenting scan if <11 weeks; 11-14 weeks; 16 week scan - endometriomas ONLY; second trimester routine scan (18-22 weeks); 30-34 weeks; any additional scans during pregnancy which resulted in either conservative management with extra scans or surgical intervention (with reason for the extra scan or for surgery documented); 0-90 days postpartum.	Diagnostic Test: Ultrasound A standardised transvaginal (supplemented with transabdominal if transvaginal is not sufficient) examination is performed. When a colour Doppler ultrasound examination is performed, the pulse repetition frequency should be 0.3-0.6 KHz. The colour Doppler gain should be increased until colour Doppler artefacts appear and then lowered until just below the reappearance of colour Doppler artefacts. Ultrasound frequency and "priority" (grey scale or colour/Power Doppler) must also be optimised when using colour/power Doppler. Doppler ultrasound should be used with all masses included, irrespective of gestational age.

Arm

Intervention/Treatment

First arm (primary objective):

First arm (primary objective): Adnexal mass scanned at 11-14 weeks. If the decision is to manage the adnexal mass conservatively, the patient is to be re-scanned once more: 0 - 90 days postpartum. In addition, the patient will be asked to enter into the third arm of the study (see below) knowing that she can opt out from that arm at any point. If she consents to participate in the third arm, she will participate in a series of longitudinal examinations as described for the third arm. All patients with a mass detected before 11 weeks will also be scanned at 11-14 weeks and can enter all three arms of the study. In this scenario, if more than one scan is performed during pregnancy before 11 weeks, only the first of several scans before 11 weeks will be included for the second and third arms of the study.

Diagnostic Test: Ultrasound

A standardised transvaginal (supplemented with transabdominal if transvaginal is not sufficient) examination is performed. When a colour Doppler ultrasound examination is performed, the pulse repetition frequency should be 0.3-0.6 KHz. The colour Doppler gain should be increased until colour Doppler artefacts appear and then lowered until just below the reappearance of colour Doppler artefacts. Ultrasound frequency and "priority" (grey scale or colour/Power Doppler) must also be optimised when using colour/power Doppler. Doppler ultrasound should be used with all masses included, irrespective of gestational age.

Second arm (secondary objective):

Second arm (secondary objective): Adnexal mass is seen for the first time during that pregnancy at any gestation. If the decision is to manage the adnexal mass conservatively, the patient is to be re-scanned once more: 0 - 90 days postpartum. For patients with a mass detected before 11 weeks, see also above (they will be re-scanned at both 11-14 weeks and at 0-90 days postpartum). In addition, the patient will be asked to enter into the third arm of the study knowing that she can opt out from that arm at any point. If she consents to this, she will participate in a series of longitudinal examinations as described for the third arm.

Diagnostic Test: Ultrasound

Third arm (secondary objective):

Third arm (secondary objective): Patients from the first and second arms who agree to enrol into the third arm i.e. longitudinal examination of an adnexal mass during pregnancy. For the purposes of the longitudinal evaluation, the time points for the ultrasound examination are: initial presenting scan if <11 weeks; 11-14 weeks; 16 week scan - endometriomas ONLY; second trimester routine scan (18-22 weeks); 30-34 weeks; any additional scans during pregnancy which resulted in either conservative management with extra scans or surgical intervention (with reason for the extra scan or for surgery documented); 0-90 days postpartum.

Diagnostic Test: Ultrasound

Outcome Measures

Primary Outcome Measures

- Estimation of the false discovery rate when the ADNEX Model is applied at 11-14 weeks. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
- Estimation of the false discovery rate when the ADNEX Model is applied at 11-14 weeks.

Secondary Outcome Measures

- Estimation of the false discovery rate when the 2-step strategy (i.e. Modified Benign Simple Descriptors followed by ADNEX) is applied at 11-14 weeks. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
- Estimation of the false discovery rate when the 2-step strategy (i.e. Modified Benign Simple Descriptors followed by ADNEX) is applied at 11-14 weeks.
- Estimation of the false discovery rate when the ADNEX Model and the 2-step strategy (i.e. Modified Benign Simple Descriptors followed by ADNEX) are applied at any time point during pregnancy; [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
- Estimation of the false discovery rate when the ADNEX Model and the 2-step strategy (i.e. Modified Benign Simple Descriptors followed by ADNEX) are applied at any time point during pregnancy;
Estimation of the ability of the ADNEX model and of the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at 11-14 weeks gestation. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
C-index
Estimation of the ability of the ADNEX model and of the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at 11-14 weeks gestation. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
(Sensitivity, Specificity)
Estimation of the ability of the ADNEX model and of the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at 11-14 weeks gestation. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
(Calibration)
Estimation of the ability of the ADNEX model and of the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at 11-14 weeks gestation. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
(Clinical utility) Net benefit.
Estimation of the ability of the ADNEX model and of the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at any time point in pregnancy. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
(C-index)
Estimation of the ability of the ADNEX model and of the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at any time point in pregnancy. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
(Sensitivity, Specificity)
Estimation of the ability of the ADNEX model and of the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at any time point in pregnancy. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
(Calibration)
Estimation of the ability of the ADNEX model and of the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at any time point in pregnancy. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
(Clinical utility) Net benefit.
- Estimation of the ability of the ADNEX model and the 2-step strategy to discriminate between benign and malignant adnexal masses when detected at any time po [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
- Estimation of the ability of the ADNEX model and the 2-step strategy (sensitivity, specificity, C-index, calibration intercept, calibration slope, clinical utility) to discriminate between benign and malignant adnexal masses when detected at any time point in pregnancy;
Evaluation of change in morphology of ovarian masses throughout pregnancy based on subjective assessment; [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
Evaluation of change in morphology of ovarian masses throughout pregnancy based on subjective assessment;
Evaluation of change throughout pregnancy and postpartum in papillations based on subjective assessment. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
Number, size (mm), colour score (1-4), and morphology.

Other Outcome Measures

Change in the ultrasound appearance of endometriomas during gestation; [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
Change in the ultrasound appearance of endometriomas during gestation;
- Occurrence of complications such as rupture, torsion, or malignancy during pregnancy in patients with conservatively treated masses (cumulative incidence illustrated by 'reverse' Kaplan-Meier curves). [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
- Occurrence of complications such as rupture, torsion, or malignancy during pregnancy in patients with conservatively treated masses (cumulative incidence illustrated by 'reverse' Kaplan-Meier curves).
- Comparison of the performance of ADNEX with CA125 and that of ADNEX without CA125. [outcome based on histology (surgery during pregnancy or within 120 days after postpartum ultrasound scan) or follow-up at postpartum scan (maximum one year after recruitment)]
(Specificity, Sensitivity, C-index, Calibration, Clinical Utility)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Inclusion Criteria:

• Consecutive patients with non-physiological adnexal masses or physiological cysts measuring 5cm or more in largest dimension;
In case of more than one mass seen, only most suspicious mass to be included OR in case of two similar masses, the one with the largest dimension or most easily accessible with ultrasound;
Previously recruited patient presenting with a different mass in subsequent pregnancy;
Age 18 years and above.

Exclusion Criteria:

• Cysts deemed to be clearly physiological WHEN smaller than 5 cm (largest diameter);
Non-adnexal masses, e.g. peritoneal inclusion cysts (when diagnosis is certain) and peritoneal carcinomatosis with no adnexal mass;
The denial or withdrawal of written informed consent;
Same cyst already recruited for p-IOTA in a previous pregnancy.
Age < 18 years