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Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening.

ABSTRACT: Liquid biopsies can detect biomarkers carrying information on the development and progression of cancer. We demonstrated that a 24 plasma-based microRNA signature classifier (MSC) was capable of increasing the specificity of low dose computed tomography (LDCT) in a lung cancer screening trial. In the present study, we tested the prognostic performance of MSC, and its ability to monitor disease status recurrence in LDCT screening-detected lung cancers.Between 2000 and 2010, 3411 heavy smokers enrolled in two screening programmes, underwent annual or biennial LDCT. During the first five years of screening, 84 lung cancer patients were classified according to one of the three MSC levels of risk: high, intermediate or low. Kaplan-Meier survival analysis was performed according to MSC and clinico-pathological information. Follow-up MSC analysis was performed on longitudinal plasma samples (n = 100) collected from 31 patients before and after surgical resection.Five-year survival was 88.9% for low risk, 79.5% for intermediate risk and 40.1% for high risk MSC (p = 0.001). The prognostic power of MSC persisted after adjusting for tumor stage (p = 0.02) and when the analysis was restricted to LDCT-detected cases after exclusion of interval cancers (p < 0.001). The MSC risk level decreased after surgery in 76% of the 25 high-intermediate subjects who remained disease free, whereas in relapsing patients an increase of the MSC risk level was observed at the time of detection of second primary tumor or metastatic progression.These results encourage exploiting the MSC test for lung cancer monitoring in LDCT screening for lung cancer.

SUBMITTER: Sestini S

PROVIDER: S-EPMC4741735 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening.

Sestini Stefano S Boeri Mattia M Marchiano Alfonso A Pelosi Giuseppe G Galeone Carlotta C Verri Carla C Suatoni Paola P Sverzellati Nicola N La Vecchia Carlo C Sozzi Gabriella G Pastorino Ugo U

Oncotarget 20151001 32

Liquid biopsies can detect biomarkers carrying information on the development and progression of cancer. We demonstrated that a 24 plasma-based microRNA signature classifier (MSC) was capable of increasing the specificity of low dose computed tomography (LDCT) in a lung cancer screening trial. In the present study, we tested the prognostic performance of MSC, and its ability to monitor disease status recurrence in LDCT screening-detected lung cancers.Between 2000 and 2010, 3411 heavy smokers enr ...[more]

PMID: 26451608

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Project description:ImportanceScreening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidity associated with cancer treatment.ObjectiveTo estimate overdiagnosis in the National Lung Screening Trial (NLST).Design, setting, and participantsWe used data from the NLST, a randomized trial comparing screening using low-dose computed tomography (LDCT) vs chest radiography (CXR) among 53 452 persons at high risk for lung cancer observed for 6.4 years, to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm.Main outcomes and measuresWe calculated 2 measures of overdiagnosis: the probability that a lung cancer detected by screening with LDCT is an overdiagnosis (PS), defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer.ResultsDuring follow-up, 1089 lung cancers were reported in the LDCT arm and 969 in the CXR arm of the NLST. The probability is 18.5% (95% CI, 5.4%-30.6%) that any lung cancer detected by screening with LDCT was an overdiagnosis, 22.5% (95% CI, 9.7%-34.3%) that a non-small cell lung cancer detected by LDCT was an overdiagnosis, and 78.9% (95% CI, 62.2%-93.5%) that a bronchioalveolar lung cancer detected by LDCT was an overdiagnosis. The number of cases of overdiagnosis found among the 320 participants who would need to be screened in the NLST to prevent 1 death from lung cancer was 1.38.Conclusions and relevanceMore than 18% of all lung cancers detected by LDCT in the NLST seem to be indolent, and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer.

Project description:ImportanceDespite the recommendations of lung cancer screening guidelines and the evidence supporting the effectiveness of population-based lung screening, a common barrier to effective lung cancer screening is that the participation rates of low-dose computed tomography (LDCT) screening among individuals with the highest risk are not large. There are limited data from clinical practice regarding whether opportunistic LDCT screening is associated with reduced lung-cancer mortality.ObjectiveTo evaluate whether opportunistic LDCT screening is associated with improved prognosis among adults with lung cancer in mainland China.Design, setting, and participantsThis cohort study included patients diagnosed with lung cancer at Weihai Municipal Hospital Healthcare Group, Weihai City, China, from 2016 to 2021. Data were analyzed from January 2022 to February 2023.ExposuresData collected included demographic indicators, tumor characteristics, comorbidities, blood indexes, and treatment information. Patients were classified into screened and nonscreened groups on the basis of whether or not their lung cancer diagnosis occurred through opportunistic screening.Main outcomes and measuresFollow-up outcome indicators included lung cancer-specific mortality and all-cause mortality. Propensity score matching (PSM) was adopted to account for potential imbalanced factors between groups. The associations between LDCT screening and outcomes were analyzed using Cox regression models based on the matched data. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis.ResultsA total of 5234 patients (mean [SD] baseline age, 61.8 [9.8] years; 2518 [48.1%] female) with complete opportunistic screening information were included in the analytical sample, with 2251 patients (42.91%) receiving their lung cancer diagnosis through opportunistic screening. After 1:1 PSM, 2788 patients (1394 in each group) were finally included. The baseline characteristics of the matched patients were balanced between groups. Opportunistic screening with LDCT was associated with a 49% lower risk of lung cancer death (HR, 0.51; 95% CI, 0.42-0.62) and 46% lower risk of all-cause death (HR, 0.54; 95% CI, 0.45-0.64).Conclusions and relevanceIn this cohort study of patients with lung cancer, opportunistic lung cancer screening with LDCT was associated with lower lung cancer mortality and all-cause mortality. These findings suggest that opportunistic screening is an important supplement to population screening to improve prognosis of adults with lung cancer.

Project description:ImportanceLung cancer screening has been widely implemented in Europe and the US. However, there is little evidence on participation and diagnostic yields in population-based lung cancer screening in China.ObjectiveTo assess the participation rate and detection rate of lung cancer in a population-based screening program and the factors associated with participation.Design, setting, and participantsThis cross-sectional study used data from the Cancer Screening Program in Urban China from October 2013 to October 2019, with follow-up until March 10, 2020. The program is conducted at centers in 8 cities in Henan Province, China. Eligible participants were aged 40 to 74 and were evaluated for a high risk for lung cancer using an established risk score system.Main outcomes and measuresOverall and group-specific participation rates by common factors, such as age, sex, and educational level, were calculated. Differences in participation rates between those groups were compared. The diagnostic yield of both screening and nonscreening groups was calculated.ResultsThe study recruited 282 377 eligible participants and included 55 428 with high risk for lung cancer; the mean (SD) age was 55.3 (8.1) years, and 34 966 participants (63.1%) were men. A total of 22 260 participants underwent LDCT (participation rate, 40.16%; 95% CI, 39.82%-40.50%). The multivariable logistic regression model showed that female sex (odds ratio [OR], 1.64; 95% CI, 1.52-1.78), former smoking (OR, 1.26; 95% CI, 1.13-1.41), lack of physical activity (OR, 1.19; 95% CI, 1.14-1.24), family history of lung cancer (OR, 1.73; 95% CI, 1.66-1.79), and 7 other factors were associated with increased participation of LDCT screening. Overall, at 6-year follow-up, 78 participants in the screening group (0.35%; 95% CI, 0.29%-0.42%) and 125 in the nonscreening group (0.38%; 95% CI, 0.33%-0.44%) had lung cancer detected, which resulted in an odds ratio of 0.93 (95% CI, 0.70-1.23; P = .61).Conclusions and relevanceThe low participations rate in the program studied suggests that an improved strategy is needed. These findings may provide useful information for designing effective population-based lung cancer screening strategies in the future.

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Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening.

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Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening.

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