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 PLCOm2012threshold >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 PLCOm2012of 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.
背景：采用低剂量螺旋计算机断层扫描（LDCT）进行肺癌筛查可降低高风险人群的死亡率。吸烟与高达90%的肺癌死亡相关，更是多种其他癌症及心脑血管与肺部疾病的关键风险因素。"吸烟者健康多重干预行动"（SMAC-1）试验旨在验证一项整合性方案的可行性与有效性，该方案基于对高风险人群吸烟相关胸心血管疾病的早期检测，并结合一级预防策略。研究采用新型多组分筛查设计，以强化传统肺癌筛查项目的框架。本文报告研究设计及基线轮次结果，重点关注肿瘤学发现。 方法：高风险人群定义为年龄＞55岁、当前吸烟者或戒烟时间＜15年且吸烟史＞30包/年的既往吸烟者，采用PLCOm2012风险阈值＞2%。通过媒体宣传和全科医生参与优化受试者招募流程。符合条件者在签署书面知情同意书后，接受心理评估、血液样本采集、自评问卷、肺功能检测及LDCT扫描。血液样本检测包括正五聚蛋白3、白细胞介素、微小RNA和循环肿瘤细胞分析。同时进行心血管风险评估和冠状动脉钙化积分测定。成本分析聚焦于不同情境下每获得一个质量调整生命年的增量成本效益比。采用"梅松纳夫风险再计算模型"确定个体化筛查间隔，并设定＜0.6%的风险阈值作为两年期筛查标准。 结果：共3228人表示参与意愿，其中1654人符合条件，最终1112人完成入组。受试者平均年龄64岁（男性/女性比例62%/38%），平均PLCOm2012风险值为5.6%。既往吸烟者与当前吸烟者分别占23%和77%。348名受试者检出至少一个肺结节。762名受试者（69%）LDCT未见临床显著异常，根据梅松纳夫风险模型（平均值=0.44%）建议其接受年度/双年度LDCT复查。122名受试者（11%）需进行肺结节主动监测。44名基线可疑结节受试者接受PET-FDG检查，其中27人接受CT引导下肺活检。最终共诊断32例恶性肿瘤，包括30例肺癌（2.7%）和2例肺外恶性肿瘤（恶性胸膜间皮瘤与胸腺瘤）。25名受试者接受肺部手术（2.25%）。值得注意的是，CT引导活检未出现假阳性病例，仅出现2例假阴性（患者接受手术后未出现分期升级）。最终病理类型包括肺腺癌（69%）、鳞状细胞癌（10%）及其他类型（21%）。病理分期显示Ⅰ期14例（47%），Ⅱ-Ⅳ期16例（53%）。 结论：LDCT持续证实其在高风险人群中安全检测早期肺癌的有效性，且假阳性风险可忽略不计。采用梅松纳夫模型对基线LDCT后肺癌发生风险进行再计算，可优化后续筛查间隔时间。SMAC-1试验为政策制定者的评估决策提供了坚实依据。我们相信这将有助于制定大规模肺癌筛查指南，为改善肺癌患者预后开辟道路。
The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round
肿瘤(癌症)患者之家