The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round

Our plain-English summary of The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round, by A. Antonicelli, P. Muriana, G. Favaro, et al (Cancers, 2024).

The study

• Authors: A. Antonicelli, P. Muriana, G. Favaro, G. Mangiameli, E. Lanza, M. Profili, F. Bianchi, E. Fina, G. Ferrante, S. Ghislandi, D. Pistillo, G. Finocchiaro, G. Condorelli, R. Lembo, P. Novellis, E. Dieci, S. De Santis, G. Veronesi
• Journal: Cancers
• Published: 2024;16(2)
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings.

Methods: High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round.

Results: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers.

Conclusions: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

In plain English

This article reported the design and baseline screening round of the SMAC-1 trial in Milan, Italy. The trial offered low-dose CT lung scans and other tests to smokers at high risk of lung cancer. Participants were over 55, were current smokers or had quit within 15 years, had more than 30 pack-years of smoking, and had a PLCOm2012-calculated lung cancer risk above 2% over six years. Of 3228 people who responded, 1654 were eligible and 1112 took part. Enrollment ran from September 2018 to September 2019. At least one lung nodule was found in 348 participants, and 762 (69%) had no clinically significant findings. In total, 32 cancers were diagnosed: 30 lung cancers (a detection rate of 2.7%), one malignant epithelioid pleural mesothelioma and one thymoma. Of 25 people who had lung surgery, 14 had stage I disease. No patient had surgery for benign disease. CT-guided biopsy gave two false negative results, and those two patients still had surgery. The article did not study or report asbestos exposure. The COVID-19 pandemic interrupted follow-up for lower-risk participants.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective lung cancer screening trial (baseline round of a multicomponent low-dose CT screening program); no comparison group results reported for this round
• Who was studied: 1112 high-risk current or former smokers who took part (out of 3228 who responded and 1654 found eligible), recruited through the IRCCS Humanitas Research Hospital, Milan area, Italy, September 2018 to September 2019
• Exposure: Cigarette smoking: age over 55, active smokers or former smokers who had quit within 15 years, more than 30 pack-years, PLCOm2012 risk above 2% in 6 years. Asbestos exposure was not studied or reported.
• Main results:
  • At least one lung nodule was found in 348 of the 1112 participants (31.2%).
  • 762 participants (69%) had no clinically significant findings on the baseline scan. Of these, 619 with a Maisonneuve risk score below 0.6% were referred to scans every two years.
  • 32 participants were diagnosed with cancer. Thirty had lung cancer (detection rate 2.7%) and two had other cancers: one malignant epithelioid pleural mesothelioma and one thymoma.
  • 25 patients had lung surgery, and 14 of them had stage I disease on final pathology.
  • No patient had surgery for benign disease (false positives at surgery 0%).
  • CT-guided biopsy gave two false negative results, and these two patients were operated on with no stage shift.
• The authors' conclusion: The authors concluded that low-dose CT continues to safely detect early-stage lung cancer in high-risk people, with a negligible risk of false positives.
• Limitations the authors state:
  • The COVID-19 pandemic made continued follow-up impossible, first for participants with a clinically not significant baseline scan and then for those with low-risk nodules.
  • Recruitment through general practitioners was very low: 194 subjects, a 6% response rate.

Topics

Medical terms in this study, explained in our Lexicon: Low-Dose CT Screening, Lung Cancer, Informed Consent, Spirometry, Interleukins, Active Surveillance, Biopsy, Pleural Mesothelioma.

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