Optimised Lung Cancer Screening to Prevent Cardiovascular and Pulmonary Diseases Coupled With Primary Prevention (SMAC-1)

This project aims to implement a health prevention program for smokers or former smokers including early detection of lung cancer, cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). The clinical activity is completed by a pre-clinical evaluation of molecular bio-markers of early diagnosis of these diseases, with the aim of strengthening the sensitivity and specificity of the screening program.

The project also includes a cost-effectiveness assessment to validate the feasibility of the program.

Since lung cancer, CVD and COPD are among the deadliest smoking-related pathologies, the program includes actions aimed at raising awareness among primary care physicians, increasing the smoking cessation rate of participating subjects to improve quality of life.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer; Chronic Obstructive Pulmonary Disease (COPD); Cardiovascular Disease (CVD)

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

Study Locations

• Italy
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Recruiting
      • Istituto Clinico Humanitas
      • Contact: Federica Cioffi; Phone Number: 02/82247371; Email: federica.cioffi@humanitas.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population should have the following inclusion criteria:

Inclusion Criteria:

• Age ≥ 55 years old and exposure to smoking more than 30 packs-year; which corresponds to 6-year risk of lung cancer, calculated according to the plco score (≥ 2%).
• Smoker or former smoker Former smokers must have ceased smoking within the 15 years prior to enrollment in the study.
• Absence of symptoms of lung cancer such as worsening of cough, hoarseness, hemoptysis and weight loss.

Description

Inclusion Criteria:

• Age ≥ 55 years old and exposure to smoking more than 30 packs-year; which corresponds to 6-year risk of lung cancer, calculated according to the plco score (≥ 2%).
• Smoker or former smoker Former smokers must have ceased smoking within the 15 years prior to enrollment in the study.
• Absence of symptoms of lung cancer such as worsening of cough, hoarseness, hemoptysis and weight loss.

Exclusion Criteria:

• Previous diagnosis of lung cancer.
• Positive extrapulmonary cancer history in the last 5 years (excluding in situ tumors or skin epidermoid tumor).
• Performing a chest CT scan in the last 18 months.
• Severe lung or extrapulmonary diseases that may preclude or invalidate appropriate therapy in case of diagnosis of malignant pulmonary neoplasia.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To implement the screening program combining lung cancer, CVD and COPD prevention	Subjects with increased risk for lung cancer, selected through an epidemiological questionnaire, sign the informed consent and their blood is collected. They then undergo LDCT and an interview at the anti-smoking center. CTs presenting with at least one non-calcified nodule are managed according to dedicated diagnostic algorithm. Nodules indicative of lung cancer will be studied with preoperative diagnosis, with surgical resection preferably performed with a minimally invasive approach. Multimodality treatment is indicated in advanced stage of disease. Subjects with normal findings are scheduled for annuals CT scan for two additional years. Cardiovascular risk will be assessed with the use of the atherosclerotic cardiovascular disease (ASCVD) score, recommended by the American College of Cardiology/American Heart Association, integrated with Reynold risk score and CAC score. The CAC score, calculated on LDCT, is used to quantify the presence of calcium through the coronary system.	from 10 Oct 2018 to 10 Oct 2021

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of circulating markers to enhance LDCT sensitivity and specificity of the screening for lung cancer, CVD and COPD early detection.	Ten ml of blood is collected before LDCT, for plasma and white blood cells. For lung cancer patients, blood is collected before treatment, at 1-6-12 months after treatment, to analyse markers for minimal residual disease or early recurrence. We will perform: CTC identification and genomic analysis. Patients are considered CTCs positive based on cytopathology of the isolated cells and detection of characteristic malignant features.; Evaluation of Serum of PTX3, measured with an original sandwich enzyme-linked immunosorbent assay (ELISA); Circulating microRNA profiling. A custom panel of 6 specific microRNAs identified in a previous study on Karolinska cohort and correlating with increase/reduction risk of CVD Mayor adverse cardiovascular events MACE will be tested in 2000 patients.; IL-2, IL-8, CRP, IL-5 and Eosinophils analyses. Interleukin-2 and-8, C-reactive protein, interleukiine-5 and eosinophils concentrations in blood are measured with ELISA kits.	from 10 Oct 2018 to 10 Oct 2021
Cost benefit analysis of LC screening program	Cost-benefit analysis of the prevention program. Direct and indirect costs associated with diagnosis and treatment of smoking-related diseases will be compared to those of a control group with disease detected after the appearance of pulmonary symptoms. The incremental cost effectiveness ratio will be evaluated in terms of QUALYS (quality of life adjusted years saved).	from 10 Oct 2018 to 10 Oct 2021

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas
• Collaborators: Ospedale San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2018
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: January 10, 2019
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: microRNAs; Minimally invasive surgery; Lung cancer screening; Cancer risk reduction; Cancer risk prevention; Cardiovascluar disease prevention; COPD prevention; Lung cancer circulating biomarkers; Low Dose Computed Tomography (LDCT)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Cardiovascular Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Lung Neoplasms
• Other Study ID Numbers: 2123

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