Advancing Lung Cancer Screening: Artificial Intelligence, Multimodal Imaging and Cutting-Edge Technologies for Early Detection and Characterization

Currently available screening programmes for lung cancer are limited by many challenges including low diagnostic accuracy, radiation exposure and high costs. New technologies in PET/CT scanners can allow cheaper and more sensitive exams with low radiation exposure. AI can be used to denoise LDCT to enhance the accuracy of imaging tests and build riskassessment models. This project aims to develop a new approach exploiting both these revolutionary advancements to bridge the existing gap in lung cancer screening. Patients in a high-risk population will be enrolled into two different cohorts undergoing LDCT scan and simultaneous [18F]FDG PET/CT on new-generation long axial field of view scanner (UO1) or screening with low LDCT only (UO2). AI will assist in image enhancement and interpretation and will develop a personalised risk-model guiding the following steps of clinical management, significantly improving early diagnosis of lung cancer, reducing mortality and healthcare costs.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Cancer Screening
• Intervention / Treatment: Procedure: LDCT scan and simultaneous [18F]FDG PET/CT on new-generation long axial field of view scanner; Procedure: LDTC only

Detailed Description

Assessment of the potential added value of low dose [18F]FDG PET/CT in the early detection of lung cancer in the screening work-up of the high-risk population. The target population (cohort 1) for the multimodal screening programme will be identified at UO1 on the basis of the PLCOM2012 prediction risk model. All patients enrolled in cohort 1 will undergo a LDCT and a simultaneous low dose [18F]FDG PET scan. Whole body [18F]FDG PET/CT will be performed according to EANM Guidelines for tumour imaging. Briefly, patients will be instructed to fast for 6 hours and to avoid strenuous physical activity for 48 hours prior to the PET/CT scan. Diabetic patients will be instructed to fast for 4 hours prior to the scan and will be instructed on the use of medications according to the institution's protocol. Blood glucose levels will be checked, [18F]FDG will be injected intravenously, and PET/CT images will be acquired after 60 minutes (± 10 minutes). A new generation long axial field of view PET/CT scanner (Omni Legend, General Electric Healthcare, Waukesha, WI, USA) will be used for whole body imaging.

The control population (cohort 2) will be identified in UO2 on the basis of the PLCOM2012 prediction risk model as previously described for cohort 1. The LDCT scan will be performed in single deep inspiratory breath hold. No intravenous contrast will be administered. LDCT images will be assessed and interpreted by at least two experienced radiologists. LDCT will be defined as positive if at least one non-calcified lung nodule >5 mm in any diameter is detected. LDCT will be defined as negative if no clinically significant morphological alterations are detected. Non-calcified nodules of 3-5mm detected by LDCT will be reported. Lung-RADS criteria will be used to classify detected lung nodules. Any other suspicious morphological alteration will be reported. The number, size, characteristics, and location of any lesion detected will be recorded for each LDCT scan. Any abnormality suggestive of clinically significant conditions other than cancer will be also reported. Sensitivity, specificity, and accuracy will be calculated by per-patient and per-lesion analysis.

• Study Type: Interventional
• Enrollment (Estimated): 334
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy
    • IRCCS San Raffaele
    • Contact: Arturo Chiti; Phone Number: 0226432716; Email: chiti.arturo@hsr.it
    • Contact: Rachele Di Donato; Phone Number: 0226433639; Email: didonato.rachele@hsr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 50 years
• PLCOm2012 risk prediction > 4%
• Be willing to adhere to the study intervention through [18F]FDG PET/CT or LDCT imaging
• Signed written informed consent form

Exclusion Criteria:

• Blood glucose levels >200 mg/dl,
• Ongoing pregnancy and breastfeeding
• Unwillingness to participate,
• Previous diagnosis of lung cancer,
• Previous CT scan within the last 24 months
• Concomitant severe clinical conditions and any condition that preclude the feasibility of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDCT scan and simultaneous [18F]FDG PET/CT on new-generation long axial field of view scanner	Procedure: LDCT scan and simultaneous [18F]FDG PET/CT on new-generation long axial field of view scanner; 18F]FDG will be injected intravenously, and PET/CT images will be acquired after 60 minutes (± 10 minutes). PET/CT images will be first analysed with the lung window to detect any findings suggestive of a lung tumour. Whole-body PET/CT images will be then analysed to detect any incidental finding in the chest as well as other anatomical areas included in the field of view. PET/CT images will be considered positive if there is at least one non-calcified lung nodule or any suspicious finding on CT scan characterised by focal [18F]FDG uptake deviating from physiological distribution or above physiological background activity.
Active Comparator: low LDCT only	Procedure: LDTC only; The LDCT scan will be performed in single deep inspiratory breath hold. No intravenous contrast will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective is to assess the diagnostic accuracy of low-dose [18F]FDG PET/CT for screening in high-risk individuals or lung cancer Time Frame:	The primary endpoint is the detection rate of [18F]FDG PET/CT for suspicious lung nodules. The sensitivity, specificity and accuracy will be calculated by a per-patient and per-lesion analysis based on the clinico-radiological follow-up. PET/CT images will be considered positive if there is at least one non-calcified lung nodule or one suspicious finding on CT scan characterised by focal [18F]FDG uptake that deviates from the physiological distribution or is above the physiological background activity. If there are no areas of increased uptake compared to physiological background activity, PET/CT images are considered negative.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the diagnostic accuracy of LDCT alone for screening in high-risk individuals or lung cancer and accuracy of [18F]FDG PET/CT for the additional detection of non-lung cancers in a high-risk population.	The sensitivity, specificity and accuracy will be calculated by a per-patient and per-lesion analysis based on the clinico-radiological follow-up. LDCT will be defined as positive if at least one non-calcified lung nodule >5 mm in any diameter is detected. LDCT will be defined as negative if no clinically significant morphological alterations are detected. Lung-RADS criteria will be used to classify detected lung nodules. PET/CT images will be considered positive if there is at least one suspicious morphological finding on CT scan characterised by focal [18F]FDG uptake that deviates from the physiological distribution or is above the physiological background activity. If there are no areas of increased uptake compared to physiological background activity, PET/CT images are considered negative.	24 months

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Collaborators: University of Salerno; University of Calabria; Fondazione Policlinico Universitario Campus Bio-Medico

Study record dates

Study Major Dates

• Study Start (Estimated): October 30, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: July 23, 2024
• First Submitted That Met QC Criteria: July 30, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): October 21, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: PNRR-MCNT2-2023-12377755

Drug and device information, study documents

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