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Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy.

ABSTRACT: BACKGROUND:The National Lung Screening Trial showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduces LC mortality. We evaluated the benefit of prolonged LDCT screening beyond 5?years, and its impact on overall and LC specific mortality at 10?years. DESIGN:The Multicentric Italian Lung Detection (MILD) trial prospectively randomized 4099 participants, to a screening arm (n?=?2376), with further randomization to annual (n?=?1190) or biennial (n?=?1186) LDCT for a median period of 6 years, or control arm (n?=?1723) without intervention. Between 2005 and 2018, 39 293 person-years of follow-up were accumulated. The primary outcomes were 10-year overall and LC specific mortality. Landmark analysis was used to test the long-term effect of LC screening, beyond 5?years by exclusion of LCs and deaths that occurred in the first 5?years. RESULTS:The LDCT arm showed a 39% reduced risk of LC mortality at 10?years [hazard ratio (HR) 0.61; 95% confidence interval (CI) 0.39-0.95], compared with control arm, and a 20% reduction of overall mortality (HR 0.80; 95% CI 0.62-1.03). LDCT benefit improved beyond the 5th year of screening, with a 58% reduced risk of LC mortality (HR 0.42; 95% CI 0.22-0.79), and 32% reduction of overall mortality (HR 0.68; 95% CI 0.49-0.94). CONCLUSIONS:The MILD trial provides additional evidence that prolonged screening beyond 5 years can enhance the benefit of early detection and achieve a greater overall and LC mortality reduction compared with NLST trial. CLINICALTRIALS.GOV IDENTIFIER:NCT02837809.

SUBMITTER: Pastorino U

PROVIDER: S-EPMC6637372 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy.

Pastorino U U Silva M M Sestini S S Sabia F F Boeri M M Cantarutti A A Sverzellati N N Sozzi G G Corrao G G Marchianò A A

Annals of oncology : official journal of the European Society for Medical Oncology 20190701 7

<h4>Background</h4>The National Lung Screening Trial showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduces LC mortality. We evaluated the benefit of prolonged LDCT screening beyond 5 years, and its impact on overall and LC specific mortality at 10 years.<h4>Design</h4>The Multicentric Italian Lung Detection (MILD) trial prospectively randomized 4099 participants, to a screening arm (n = 2376), with further randomization to annual (n = 1190) ...[more]

PMID: 30937431

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Project description:BACKGROUND:The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. METHODS:From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. RESULTS:The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). CONCLUSIONS:Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).

Project description:ImportanceThe potential to achieve greater reductions in lung cancer mortality than originally estimated by the National Lung Screening Trial with the inclusion of more Black participants stresses the importance of improving access to lung cancer screening for Black current and former smokers, a population presently with the highest lung cancer morbidity and mortality.ObjectiveTo estimate lung cancer and all-cause mortality reductions achievable with lung cancer screening via low-dose computed tomography (LDCT) of the chest in populations with greater proportions of Black screening participants than seen in the original NLST cohort.Design, setting, and participantsThis cohort study was conducted as a secondary analysis of existing data from the National Lung Screening Trial, a large national randomized clinical trial conducted from 2002 through 2009. NLST participants were current or former smokers, aged between 55 and 74 years, with at least 30 pack-years of smoking history and less than 15 years since quitting. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% CIs of lung cancer mortality and all-cause mortality according to LDCT screening compared with chest radiograph screening. Using a transportability formula, we estimated outcomes for LDCT screening among hypothetical populations by varying the distributions of Black individuals, women, and current smokers. Data were analyzed between September 2020 and March 2021.ExposuresLung screening with LDCT of the chest compared with chest radiography.Main outcomes and measuresLung cancer mortality and all-cause mortality.ResultsThis study included a total of 53 452 participants enrolled in the NLST. Of 2376 Black individuals and 51 076 non-Black individuals, 21 922 (41.0%) were women and the mean (SD) age was 61.4 (5.0) years. Over a median (interquartile range) follow-up of 6.7 (6.2-7.0) years, LDCT screening among the synthesized population with a higher proportion of Black individuals (13.4%, mirroring US Census data) was associated with a greater relative reduction of lung cancer mortality (eg, Black individuals: HR, 0.82; 95% CI, 0.72-0.92; vs entire NLST cohort: HR, 0.84; 95% CI, 0.76-0.96). Further reductions in lung cancer mortality by LDCT screening were found among a hypothetical population with a higher proportion of men or current smokers, along with a higher proportion of Black individuals (ie, 60% Black participants; 20% to 40% women) (HR, 0.68; 95% CI, 0.48-0.97).Conclusions and relevanceThe potential to achieve greater reductions in lung cancer mortality than originally estimated by the NLST with the inclusion of more Black participants stresses the critical importance of improving access to lung cancer screening for Black current and former smokers.

Project description:PurposeThis study aimed to describe the survival outcomes and factors associated with prognosis in patients undergoing pulmonary metastasectomy with colorectal cancer (CRC) in a cancer center in South America.Material and methodsA retrospective analysis of patients that underwent lung metastasectomy due to CRC at National Cancer Institute (INC), Colombia between 2007 and 2017 was performed and Kaplan-Meier survival analysis along with log-rank test and Cox regression multivariate analysis were completed.ResultsSeventy-five patients with colorectal adenocarcinoma were included in the study. Of them, 57.3% were women with a median age of 62 years [interquartile ranges (IQR): 18.5]. For 45.3% the adenocarcinoma was located in the rectum and 29.3% had stage IV at diagnosis. 56% had a history of controlled extrapulmonary metastasis and 20% of the cases had a history of the metastasis of the liver. The median follow-up was 36.8 months (IQR: 27.4). Three-year and five-year overall survival (OS) was 57.5% [95% confidence interval (CI), 47.0-70.4] and 33.2% (95% CI, 23.4-47.2), respectively. Patients with bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy carcinoembryonic antigen (CEA), history of liver metastasis, and disease-free interval (DFI) ≤12 months had worse OS. Three-year and five-year disease-free survival (DFS) was 30.1% (95% CI, 20.8-43.6) and 21.6% (95% CI, 13.0-35.9), respectively. Bilateral, more than one pulmonary metastasis, and patients with stage IV at diagnosis had the worst DFS. Multivariate analysis in the Cox regression model showed that abnormal postmetastasectomy CEA [Hazard Ratio (HR):1.97, 95% CI, 1.01-3.86, p = 0.045] and DFI ≤ 12 months (HR: 3.08, 95% CI, 1.26-7.53, p = 0.014) were independent factors for worst OS.ConclusionsThe OS found falls within the wide range described in the world literature but interestingly it falls at the bottom end of this range. The factors associated with worst survival were identified as bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy CEA, history of liver metastasis, and DFI ≤12 months.Contribution to the fieldPulmonary metastasectomy is the standard of care in patients with metastatic CRC. However, the literature supporting this conduct is based on retrospective studies and the only randomized controlled trial conducted to date was stopped due to poor recruitment. Limited information is available in South America about survival and factors associated with prognosis in patients with metastatic CRC. While this study is another series that adds to the many studies across the world that describe the use of pulmonary metastasectomy in CRC, it presents critical data as it is one of the few studies carried out in South America. As described in a wide range of world literature, OS found falls in patients that underwent lung metastasectomy due to CRC however; interestingly, in the South American population analyzed here it falls at the bottom end of this range. This may be explained by a large number of patients included with a history of extrapulmonary metastasis as well as may reflect inadequate patient access to reference cancer centers in Colombia. Factors associated with worst survival in our population were bilateral, more than one pulmonary metastasis, abnormal postmetastasectomy CEA, history of liver metastasis, and interval from diagnosis to development of pulmonary metastasis ≤12 months.

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Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy.

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Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy.

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