Machine Learning Algorithms Incorporating Radiomic Ultrasound Features (R-IOTA)

August 27, 2026 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Machine Learning Algorithms Incorporating Radiomic Ultrasound Features for Clinical Precision in Diagnosing Adnexal Tumors and Optimizing Patient Management: a Multicenter IOTA Study

Adnexal masses represent a frequent clinical finding and their preoperative characterization remains challenging. Accurate discrimination between benign and malignant adnexal masses is essential to optimize patient management, avoid unnecessary surgery, and ensure appropriate referral of patients with suspected malignancy to specialized centers.

This multicenter international observational study aims to evaluate the diagnostic performance and clinical utility of ultrasound-based machine learning (ML) models incorporating radiomic features for the characterization of adnexal masses. The study will develop and validate artificial intelligence (AI)-based models using ultrasound imaging data to support the preoperative classification of adnexal masses.

The primary objective of the study is to evaluate the ability of ultrasound-based ML models to distinguish between benign and malignant adnexal masses.

Secondary objectives include the evaluation of additional AI-based classification models among masses identified as malignant, including the discrimination between borderline tumors, primary invasive malignancies, and metastatic lesions. Furthermore, the study will assess the ability of AI models to differentiate primary epithelial ovarian carcinoma from non-epithelial ovarian malignancies among cases classified as primary ovarian cancer.

The clinical utility of the developed models will be assessed using decision curve analysis. In addition, a retrospective post hoc evaluation will be performed in an independent prospective external validation cohort to explore the potential clinical impact of an AI-based preoperative model for the management of adnexal masses. This evaluation will compare AI model outputs with actual clinical decisions made during routine care, without influencing patient management or altering the diagnostic and therapeutic pathway.

The post hoc clinical impact analysis will assess diagnostic concordance between AI predictions and clinicians' preoperative assessments, the potential proportion of avoidable surgical procedures according to AI model predictions, surgical and follow-up complications, and cost-effectiveness through comparison of healthcare resource utilization between standard clinical management and a reconstructed AI-supported scenario.

Patient-reported outcomes will also be evaluated, including patient satisfaction regarding diagnostic communication, clarity of information provided, and perceived quality of care within the standard clinical management pathway.

Overall, this study aims to investigate whether ultrasound-based AI models integrating radiomic features can improve the characterization of adnexal masses and provide clinically useful tools to support personalized and efficient patient management.

Study Overview

Status

Not yet recruiting

Conditions

Adnexal Masses

Detailed Description

Epithelial ovarian cancer and other tubo-ovarian malignancies represent a major clinical challenge among gynecological cancers, particularly in developed countries, where they are associated with substantial morbidity and mortality. Despite advances in diagnosis and treatment, the prognosis of advanced tubo-ovarian cancer remains poor, with overall 5-year survival rates ranging approximately between 30% and 45%. Early and accurate characterization of adnexal masses is therefore essential to optimize clinical management, ensure appropriate referral of patients with suspected malignancy to specialized centers, and avoid unnecessary surgical procedures in patients with benign disease.

International scientific societies, including the European Society of Gynaecological Oncology (ESGO), International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), International Ovarian Tumor Analysis (IOTA) group, and European Society of Gynaecological Endoscopy (ESGE), recommend ultrasound examination as the first-line imaging modality for the evaluation and risk stratification of adnexal masses. Expert ultrasound assessment and validated prediction models, such as the Assessment of Different NEoplasias in the adneXa (ADNEX) model developed by the IOTA group, have demonstrated high diagnostic accuracy for the discrimination between benign and malignant adnexal lesions and have shown the ability to further classify malignant masses according to different tumor categories.

However, ultrasound-based characterization of adnexal masses remains dependent on the availability of expertise and may be influenced by interobserver variability. The development of objective and reproducible diagnostic tools capable of extracting additional information from ultrasound images may therefore represent an important opportunity to improve diagnostic consistency and support clinical decision-making.

In recent years, radiomics has emerged as an innovative approach for the quantitative analysis of medical images. Radiomic techniques allow the extraction of high-dimensional imaging features that may capture subtle patterns and characteristics not readily identifiable through conventional visual interpretation. When combined with machine learning (ML) algorithms, radiomic features derived from ultrasound images may provide new opportunities for automated lesion characterization and improved prediction of tumor behavior.

Preliminary studies investigating ultrasound radiomics and artificial intelligence approaches in adnexal masses have shown promising results; however, currently available evidence is limited by small sample sizes, single-center designs, heterogeneous methodologies, and insufficient external validation. Large multicenter international studies are needed to evaluate the reproducibility, generalizability, and clinical applicability of AI-based approaches in this setting.

The present multicenter international IOTA study aims to develop and validate ultrasound-based machine learning models integrating radiomic features for the characterization of adnexal masses. The study will collect and analyze ultrasound imaging data from participating centers and will evaluate the ability of AI-based models to provide accurate and reproducible classification of adnexal lesions.

The primary objective of the study is to assess the performance of ultrasound-based machine learning models incorporating radiomic features in distinguishing benign from malignant adnexal masses.

Secondary objectives include the evaluation of additional AI-based models for the characterization of malignant adnexal masses, including the discrimination between borderline tumors, primary invasive malignancies, and metastatic lesions among masses classified as malignant by the primary model. Furthermore, the study aims to evaluate the ability of AI-based approaches to differentiate primary epithelial ovarian carcinoma from non-epithelial ovarian malignancies among lesions classified as primary ovarian cancer.

The study will also investigate the potential clinical utility of the developed models through decision curve analysis, evaluating the potential net benefit of AI-assisted prediction strategies across different clinical decision thresholds.

An independent prospective external validation cohort will be used to further evaluate the generalizability of the developed models and to explore their potential impact in a real-world clinical setting. This analysis will be performed retrospectively and post hoc, comparing AI model outputs with actual clinical decisions made during routine patient care. Importantly, AI predictions will not be available to clinicians and will not influence diagnostic pathways, treatment decisions, surgical planning, or patient management.

The retrospective clinical utility assessment will include evaluation of the agreement between AI predictions and clinicians' preoperative assessment of malignancy based on available clinical and imaging information. In addition, the study will explore the potential proportion of surgical procedures that could have been avoided according to AI model predictions, while maintaining patient safety. Surgical and follow-up outcomes, including intraoperative and postoperative complications and complications occurring during follow-up, will also be evaluated, including specific analyses of cases classified retrospectively as potentially unnecessary procedures.

A health economic evaluation will be performed to compare healthcare resource utilization and costs associated with standard clinical management with a reconstructed scenario based on AI model outputs. This analysis aims to explore the potential cost-effectiveness of AI-supported strategies for the management of adnexal masses.

Patient-reported outcomes will also be assessed to evaluate aspects related to the patient experience during standard clinical management, including satisfaction with diagnostic communication, clarity of information provided, and perceived quality of care.

Overall, this study aims to provide robust multicenter international evidence regarding the performance, reproducibility, and potential clinical utility of ultrasound-based machine learning models incorporating radiomic features for the evaluation of adnexal masses. The ultimate goal is to investigate whether AI-assisted approaches may contribute to a more standardized, accurate, and personalized diagnostic pathway while supporting appropriate allocation of healthcare resources.

Study Type

Observational

Enrollment (Estimated)

12000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: ANTONIA CARLA TESTA, Professor
Phone Number: +390630156399
Email: antoniacarla.testa@policlinicogemelli.it

Study Locations

Italy
- - Roma, Italy, 00168
    - Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    - Contact:
      
      Antonia Carla Testa, Professor
      
      Phone Number: +39 063015639

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

Patients with adnexal masses

Description

Inclusion Criteria:

Patients with an adnexal mass identified at ultrasound examination who either undergo surgery within 6 months of the ultrasound or have at least 1 year of follow-up. This includes: the retrospective cohort recruited from IOTA centers, and the prospective cohort recruited from nonIOTA centers.
Age ≥ 18 years old
Availability of at least one grayscale digital ultrasound image clearly depicting the adnexal mass.
Signed written informed consent

Exclusion Criteria:

Patients without available digital ultrasound images.
Patients without an outcome (final histology or follow up at one year).
Absence of written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Development Cohort Patients with adnexal masses evaluated at participating centers with available ultrasound imaging data and reference diagnosis. Data from this cohort will be used for the development and internal validation of ultrasound-based machine learning models incorporating radiomic features.
External Validation Cohort Independent prospective cohort of patients with adnexal masses enrolled at participating centers. This cohort will be used for external validation of the developed ultrasound-based machine learning models and assessment of their performance and generalizability. AI model outputs will not influence clinical management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of an ultrasound-based machine learning model for discrimination of benign and malignant adnexal masses Time Frame: At final diagnosis or completion of 1-year follow-up	Diagnostic performance of a machine learning model incorporating ultrasound radiomic features for distinguishing benign from malignant adnexal masses, assessed against the reference diagnosis. Performance will be evaluated using area under the receiver operating characteristic curve (AUC-ROC), accuracy, sensitivity, specificity, and calibration.	At final diagnosis or completion of 1-year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

Principal Investigator: Antonia Carla Testa, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

September 1, 2029

Study Registration Dates

First Submitted

July 31, 2026

First Submitted That Met QC Criteria

August 27, 2026

First Posted (Actual)

August 28, 2026

Study Record Updates

Last Update Posted (Actual)