Alberta Lung Cancer Screening Program

Study Overview
=================
Brief Summary
-----------------
Lung cancer is the leading cause of cancer death in North America and in the world. The vast majority of lung cancers are associated with cigarette smoking. Unfortunately, the majority of lung cancers are detected at an advanced stage when they have a very poor prognosis. A substantial amount of data has been reported on low-dose computed tomography (LDCT) screening. Yet endorsement of lung cancer screening has not been universal because of outstanding concerns which need to be addressed. Our study will aim to screen at risk Albertans for lung cancer with LDCT scan at baseline, year 1 and year 2 while attempting to fill some knowledge gaps on this topic.

Detailed Description
-----------------
Lung cancer is the leading cause of cancer death in North America and in the world. The vast majority of lung cancers are associated with cigarette smoking. Lung cancer incidence and mortality rates are similar because lung cancer is a highly fatal disease. Unfortunately, the majority of lung cancers are detected at an advanced stage when they have a very poor prognosis. A substantial amount of data has been reported on low-dose computed tomography (LDCT) screening. The results of the National Lung Screening Trial (NLST) showed a 20% reduction in mortality from lung cancer with LDCT screening in addition to a 6.7% decrease in all-cause mortality, the first ever screening intervention to demonstrate an improvement in this latter outcome. Yet endorsement of lung cancer screening has not been universal. Although the NLST results are encouraging, more investigation is needed. The objectives of this study are to prospectively compare the performance of a lung cancer risk prediction model (RPM) vs. NLST criteria to inform optimal inclusion criteria for a clinical screening program; to prospectively compare a novel screening based nodule malignancy probability calculation which has been developed in the Pan-Canadian Early Detection of Lung Cancer study vs. NLST criteria; to complete a randomized controlled trial as a substudy comparing an intensive tobacco cessation counseling program to a usual care arm for subjects with ongoing tobacco use; to perform a cost analysis evaluating the incremental costs associated with LDCT screening for lung cancer compared to no screening; to determine the average cost associated with incidental findings, false positive findings and lung cancers found during the screening period; and to compare cost implications of both screening enrollment criteria. The backbone of this research project will be the screening of at risk individuals for lung cancer with LDCT scan. Eight hundred at risk Albertans will be screened at baseline, year 1 and year 2. Additional clinical LDCT or other investigations may result from findings on the study CT scans.

Official Title
-----------------
Alberta Lung Cancer Screening Program

Conditions
-----------------
Lung Neoplasms, Respiratory Tract Neoplasms

Intervention / Treatment
-----------------
* Procedure: Computed Tomography
* Behavioral: Active smokers - Smoking cessation arm
* Behavioral: Active smokers - Control arm


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects between the ages of 55 and 80 with a risk prediction model (RPM) ≥1.5% (≥ 1.5% risk of lung cancer over 6 years) OR NLST criteria (age 55-74; ≥ 30 pack-year smoking history; ongoing smoking or quit within 15 years). Ability to provide informed consent and participate in study procedures. Exclusion Criteria: Any medical condition, such as severe heart disease (e.g. unstable angina, chronic congestive heart failure), severe lung disease or lung disease requiring supplemental oxygen that in the opinion of the physician unlikely to benefit from screening due to shortened life-expectancy from the co-morbidities or inability to tolerate diagnosis and treatment of a screen detected abnormality. European Cooperative Oncology Group performance status > 2. History of lung cancer. Have had other cancer or treatment for cancer within the past 5 years with the exception of the following cancers: non-melanomatous skin cancer, localized prostate cancer, carcinoma in situ (CIS) of the cervix, or superficial bladder cancer. Treatment of the exceptions must have ended > 6 months before registration into this study. Pregnancy. Hemoptysis in past 12 months. Unexplained weight loss >15 pounds / 7kg in past 12 months. Unwilling to have a LDCT of chest. Unwilling to sign a consent. Have had a CT scan of the chest in the last 2 years.

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Screening arm<br>Annual low dose screening chest CT scan x 3. | Procedure: Computed Tomography<br>* Low dose chest CT screening annually x 3<br>|
| Experimental: Smoking cessation counseling<br>Active smokers randomized to this arm will be contacted by a trained smoking cessation counselor and offered cessation support and advice. | Behavioral: Active smokers - Smoking cessation arm<br>* Phone based smoking cessation counseling<br>|
| Active Comparator: Smoking cessation control<br>Active smokers randomized to this arm will receive general information on available smoking cessation resources. | Behavioral: Active smokers - Control arm<br>* Subjects will be provided with general information on available smoking cessation resources<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of screening enrollment criteria (Risk prediction model (RPM) vs. NLST criteria) | The proportion of individuals selected by RPM or NLST will be calculated as the number of subjects qualifying and consenting to the screening intervention / total number of subjects enrolled with either criteria. Superiority of the risk prediction model over NLST criteria will be considered established if it identifies at least as many cases of lung cancer as the NLST while sampling fewer individuals. | 5 years | 
| Randomized trial of smoking cessation intervention in screened individuals (smoking status [smoking rates assessed via questionnaire and abstinence confirmed by saliva nicotine or exhaled carbon minoxide]) | The primary study endpoint will be an assessment of smoking status at 12 months following randomization. Smoking rates will be assessed via phone questionnaire and abstinence confirmed by saliva nicotine test or exhaled carbon monoxide in subjects using nicotine replacement therapies (to avoid false positive nicotine test). | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of nodule risk calculator | We will prospectively validate a nodule risk calculator by comparing the proportion of baseline CT examinations reported as positive by the calculator vs. NLST criteria on a per subject basis | 3 years | 
| Health Economics Analysis (healthcare payer and all direct health-care related cost) | Costs will be estimated for the cohort of individuals who enroll in the screening program and consent to receive a LDCT scan. Costs will also be estimated for a group of individuals who are eligible for the screening program however do not undergo screening. We will include costs for all relevant health care categories for a 2 year period from the date of risk stratification. The perspective of the analysis will be that of the healthcare payer and all direct health-care related costs would be captured and reported in Canadian dollars. | 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lung Cancer, Screening, Computed Tomography