AI for Lung Cancer Risk Definition in Computed Tomography Screening Programs

Artificial Intelligence Tools Integrating Blood Biomarkers and Radiomics to Define Lung Cancer Risk in Computed Tomography Screening Programs

Low-dose computed tomography (LDCT) lung cancer (LC) screening can reduce mortality among heavy smokers, but there is a critical need to better identify people at higher risk and to reduce harms related to management of benign nodules. The most promising strategy is to combine novel tools to optimize clinical decisions and increase the benefit of screening.

In this respect, the investigators already demonstrated that the combination of baseline LDCT features with a minimal invasive microRNA blood test was able to more precisely estimate the individual risk of developing LC. The investigators posit that additional immune-related and radiologic features can be integrated with the help of artificial intelligence (AI) to further implement LDCT screening strategies. The project will answer whether the combination of (bio)markers of different origin can predict LC development at baseline and over time, indicate which screen-detected lung nodules are likely to be malignant and ultimately reduce LC and all cause mortality.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer; Blood Biomarkers
• Intervention / Treatment: Diagnostic test: Artificial Intelligence risk model

Detailed Description

Lung cancer constitutes 28% of all cancer deaths in Europe, with 70% of patients diagnosed at advanced stages and a mere 21% 5-year survival rate. Despite smoking's causative link to almost 90% of cases, global smoking rates persist, posing a long-term public health challenge. Our focus lies in refining lung cancer risk assessment using blood-based biomarkers, particularly circulating microRNAs (miRNAs) and C-reactive protein. Biennial LDCT screenings and blood tests predicting lung cancer risk have shown effectiveness, as seen in our pioneering work within the BioMILD trial since 2013.

The BioMILD trial, encompassing 4119 volunteers, combines LDCT and microRNA biomarkers, demonstrating feasibility and safety over 4 years. Our current endeavor aims to develop a predictive model for LDCT-detected high-risk lung nodules, incorporating blood, functional, and radiomics biomarkers. Leveraging the BioMILD trial's biorepository, imaging database, and 20 patient-derived xenografts (PDXs), the investigators utilize advanced artificial intelligence (AI) tools for comprehensive analysis. This approach, involving 400 subjects with solid and sub-solid LDCT lung nodules, including 100 baseline-identified cancer patients, is crucial.

By combining blood-based biomarkers, radiologic parameters, clinical features, and AI tools, the investigators aim to create a robust model. This model will be validated using an independent set of 100 subjects (25 with and 75 without lung cancer) from the ongoing SMILE screening trial. If successful, our vision is to prospectively implement this panel in clinical contexts where it proves beneficial. Our mission is to reduce lung cancer mortality, optimizing screening interventions with novel, non-invasive tools for all high-risk individuals while minimizing costs and radiation exposure-related harms.

Aim 1 Assessment of an Immune Signature Classifier (ISC) on peripheral blood mononuclear cell (PBMC) samples collected from screen detected solid and sub-solid LDCT lung nodules and integration of ISC with existing biomarkers such as the MSC test and the c-Reactive Protein (cRP).

Aim 2 Evaluation of radiologic features and other LDCT markers related to respiratory and cardiovascular disorders.

Aim 3 Development of a risk classifier using AI tools based on combination of blood biomarkers, imaging and clinical data to improve LDCT screening sensitivity and positive predictive value.

• Study Type: Observational
• Enrollment (Actual): 650

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

LDCT screening volunteers enrolled in the BioMILD trial (clinicaltrial.gov NCT02247453) with solid and sub-solid baseline LDCT lung nodules, including baseline-identified cancer patients, in the SMILE trial (clinicaltrial.gov NCT03654105) and in the RISP trial (clinicaltrial.gov NCT05766046).

Description

Inclusion Criteria:

• current heavy smokers of ≥ 30 pack/years or former smokers with the same smoking habits having stopped from 10 years or less;
• current heavy smokers of ≥ 20 pack/years or former smokers with the same smoking habits having stopped from 10 years or less with additional risk factors such as family history of lung cancer, prior diagnosis of chronic obstructive pulmonary disease (COPD) or pneumonia;
• Suspected solid and sub-solid LDCT lung nodules.

Exclusion Criteria:

-

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intervention cohort; LDCT screening volunteers enrolled in the BioMILD trial (clinicaltrial.gov NCT02247453) with solid and sub-solid baseline LDCT lung nodules, including baseline-identified cancer patients.	Diagnostic test: Artificial Intelligence risk model; Combining blood-based biomarkers, radiologic parameters, clinical features, and AI tools to create a robust model to predict lung cancer risk.
Validation cohort; LDCT screening volunteers enrolled in the SMILE trial (clinicaltrial.gov NCT03654105) and in the RISP trial (clinicaltrial.gov NCT05766046).	Diagnostic test: Artificial Intelligence risk model; Combining blood-based biomarkers, radiologic parameters, clinical features, and AI tools to create a robust model to predict lung cancer risk.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 1	Development of a risk classifier using AI tools based on combination of blood biomarkers, imaging and clinical data to improve LDCT screening sensitivity and positive predictive value.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 2	Evaluation of radiologic features and other LDCT markers related to respiratory and cardiovascular disorders.	30 months
Aim 3	Assessment of an Immune Signature Classifier (ISC) on peripheral blood mononuclear cell (PBMC) samples collected from screen detected solid and sub-solid LDCT lung nodules and integration of ISC with existing biomarkers such as the MSC test and the c-Reactive Protein (cRP).	30 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Collaborators: University of Milano Bicocca
• Investigators: Principal Investigator: Ugo Pastorino, MD, Fondazione IRCCS Istituto Nazionale dei tumori di Milano

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2023
• Primary Completion (Actual): October 30, 2024
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: lung cancer; microRNA; Artificial Intelligence; screening; Low-dose computed tomography; Immune profiling
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: INT 0083/23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No