This is a single arm screening study. All eligible participants will be subjected to low dose CT (LDCT) screening and biomarker testing.
The primary aim of the study is to determine the feasibility of conducting LDCT screening in at-risk populations for lung cancer in Singapore:
* For the smoker population, LDCT screening for lung cancer will be implemented in accordance to Academy of Medicine, Singapore screening test guidelines with the aim of investigating the feasibility of instituting lung cancer screening clinical service in Singapore. * For the non-smoker population, LDCT screening for lung cancer will be introduced to systematically collect baseline data to better understand and provide evidence for lung adenocarcinoma in never-smoker phenotype that is unique to East Asia/Singapore. This will help address unmet needs in local population research as reported by Academy of Medicine, Singapore, to validate risk factors and inform future screening guidelines for the at-risk population.
Screening results will be reported based on Lung CT Screening Reporting \& Data System (Lung-RADS).
Participant is willing and able to give informed consent for participation in the study
Male or female, aged 50-80 years of age
No prior history of cancer, or cancer free in the last 5 years and not currently on cancer treatment
ECOG 0/1
Uncontrolled medical comorbidity on enrolment
Previous diagnosis of cancer
Bleeding diathesis that will preclude blood sampling
Fear of blood draw or needles
Single group
Low-dose CT of the Chest (LDCT) + Sampling for Biomarker Assays
Diagnostic testLDCT scan results will be reported based on the Lung-RADS classification. Participants will be stratified into various Lung-RADS groups based on the CT appearance and size of nodules. An alphanumeric Lung-RADS score will be assigned to each subject which will guide the downstream management of screened participants. All subjects will be required to donate drawn blood samples (up to 30 ml) at every LDCT visit during screening surveillance, and at every LDCT/CT scan and/or biopsy visits during clinical surveillance for blood-based biomarker assays development and characterization. Subjects may also be asked to provide a sample of urine, saliva and breath for biomarker discovery.
Feasibility of conducting Low Dose CT (LDCT) screening in at-risk populations (1).
Diagnostic accuracy of LDCT at baseline.
Feasibility of conducting LDCT screening in at-risk populations (2).
Compliance with LDCT screens for patients with lung-RADS 1 from baseline till end of screening surveillance.
The utility of blood-based biomarker assays in improving the performance of LDCT to detect lung cancer and discriminate risk of malignancy. (1)
Diagnostic accuracy and discrimination ability of biomarker assay in the detection of lung cancer will be assessed via sensitivity, specificity, PPV, NPV and area under curve (AUC) of the receiver operating characteristic curve.
The utility of blood-based biomarker assays in improving the performance of LDCT to detect lung cancer and discriminate risk of malignancy. (2)
Changes in biomarker levels over time in relation to lung cancer diagnosis. Time series plot of biomarker levels by whether participants have lung cancer diagnosed will be created. Linear mixed effect models will be used to assess the changes in biomarker levels over time in the group of participants with lung cancer diagnosed, and to compare whether the changes observed are different from those experienced by the group of patients with no lung cancer diagnosed.
Comparison of the diagnostic performance of each combination of a biomarker assay and LDCT screening against that of LDCT screening.
A biomarker assay that can accurately diagnose lung cancer will then be combined with LDCT screening via a re-definition of what constitute a positive screening test (e.g. Lung-RADS 3 to 4X or biomarker assay above a certain threshold). The additional diagnostic value of a biomarker assay will be assessed by comparing the diagnostic performance of the combination of the biomarker assay and LDCT screening against that based on LDCT screening alone.
The lung cancer detection rate at each round of screening.
Screen detected lung cancer rate at baseline, and interval cancers detected between screening rounds.
To evaluate if computer-aided diagnosis strategies can enhance LDCT screening.
Identification of radiomic biomarkers that can improve the diagnostic accuracy of LDCT screening. Screening LDCT imaging data as well as data from subsequent staging imaging studies of participants with proven screening-detected lung cancer will be evaluated. The lung tumour(s) will be segmented and quantitative features extracted using semi-automated software systems. The extracted quantitative features will be analysed in combination with clinical and pathological data to develop models that predict tumour characteristics or treatment response.
To determine the feasibility of screening for concomitant coronary artery disease.
LDCT-based calcium scoring in cardiovascular disease risk assessment.
To study gene-environment-lifestyle interactions in the screened population.
For gene-environment-lifestyle interaction analysis, interactions between genetic variants (by means of genotyping of samples collected) and environmental risk factors (gathered from Life-Style questionnaire administered) will be assessed using a 2 degree of freedom joint test, which provides a joint test for genotype and genotype-environment interaction terms. GWAS association tests will be performed using significant SNPs that were previously reported in the literature and combined with questionnaire data on environmental exposures and lifestyles. All statistical analyses will be conducted using R version 3.5. All tests are considered significant with a p-value of less than 0.06. False discovery rates (FDR) will be calculated using the Benjamini and Hochberg method to account for multiple comparisons.
To determine cost-effectiveness of LDCT screening for early diagnosis.
Quality-adjusted life-years (QALYs) gained.
Click on the lead sponsor to view all of their trials.
National Cancer Centre, Singapore
Lead sponsor
Singapore General Hospital
Collaborator
National Heart Centre Singapore
Collaborator
Changi General Hospital
Collaborator
Sengkang General Hospital
Collaborator
Genome Institute of Singapore
Collaborator
National University of Singapore
Collaborator
Duke-NUS Graduate Medical School
Collaborator
Tan Tock Seng Hospital
Collaborator
