HANSE - Holistic Implementation Study Assessing a Northern German Interdisciplinary Lung Cancer Screening Effort

Study Overview
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Brief Summary
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The HANSE study is primarily intended as a pilot to provide evidence that a holistic and effective lung cancer screening program can be implemented in Germany and that such a screening program can be integrated in the current infrastructure of certified lung cancer centers.

Detailed Description
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Germany has a long history of offering screening programs for cancers, such as breast, colorectal, and, more recently, cervical and skin cancer. Screening for lung cancer, however, which causes more deaths than any other cancer in men and is the second leading cancer death in women (not far behind breast cancer), has not been implemented to date. Only very recently, Institute for Quality and Efficiency in Healthcare (IQWiG) in a preliminary assessment of low-dose CT screening, concluded that the benefits from screening outweigh potential risks. However, an implementation of a national lung cancer screening program, which would be covered by the general health insurance, will likely not be implemented before 2022. Nonetheless, the IQWiG report also comments on important criteria for implementing lung cancer screening in Germany using low-dose CT: It would be necessary to determine criteria that define a high-risk population. Various risk forecasting models are currently being propagated to enable a more precise selection of high-risk individuals. Their reliability and repeatability needs to be checked. Integration of access to a smoking cessation program. Quality assurance measures must be taken into account, including standardized protocols for the evaluation of the CT images and the subsequent follow-up checks as well as the invasive diagnostic tissue sampling procedures. The HANSE study is primarily intended as a pilot to provide evidence that a holistic and effective lung cancer screening program can be implemented in Germany and that such a screening program can be integrated in the current infrastructure of certified lung cancer centers.

Official Title
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HANSE - Holistic Implementation Study Assessing a Northern German Interdisciplinary Lung Cancer Screening Effort, Population-based Screening Study -Prospective, Randomized Comparator Controlled

Conditions
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Lung Cancer

Intervention / Treatment
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* Radiation: Low-dose CT screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged 55-79 years Current or former smokers Subjects with calculated risk score PLCOM2012 ≥1.58% (6 yrs.) or NELSON inclusion criteria (current or former smokers [those who had quit ≤10 years ago] who had smoked >15 cigarettes a day for >25 years or >10 cigarettes a day for >30 years). Able and willing to give written informed consent In addition, non-qualifying subjects fulfilling inclusion criteria 1 (age), 2 (smoking history) and 4 (consent), but do not meet the inclusion criterion 3 (risk too low) will be asked to volunteer by contributing long-term outcome data informing of the development of lung cancer or death from lung cancer (about n=7100 randomly selected from all 3 centers, low-risk group). These subjects will be contacted via mail after a minimum of 5 year follow up to inquire if they developed lung cancer in the time between their recruitment and present. Non-responders will be followed by local registries and by phone. New lung cancer cases will be verified using official hospital or cancer registry documents. Exclusion Criteria: Comorbidity, which would unequivocally contraindicate either screening or treatment if lung cancer is detected. History of chest CT within the past year preceding the invitation. Inability to undergo non-contrast CT (e.g. ≥ 200 kg body weight, inability to lie flat). Pregnancy Risk of non-compliance with study procedures. Unable to give written consent Patient's inability to fill in the questionnaire self-dependent Limited knowledge of the German language Inability to travel, residents of care facilities, etc.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Population-based Screening Study -Prospective, randomized comparator controlled
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Reporting group (coronary calcium score and emphysema score)<br>Coronary calcium score and emphysema score are reported to subjects | Radiation: Low-dose CT screening<br>* Low-dose computed tomography with lung nodule evaluation (LungRADS1.1, highrisk score group), randomized reporting of coronary artery calcium score and emphysema score<br>|
| Other: Reporting group (coronary calcium score only)<br>Only coronary calcium score is reported to subjects | Radiation: Low-dose CT screening<br>* Low-dose computed tomography with lung nodule evaluation (LungRADS1.1, highrisk score group), randomized reporting of coronary artery calcium score and emphysema score<br>|
| Other: Reporting group (emphysema score only)<br>Only emphysema score is reported to subjects | Radiation: Low-dose CT screening<br>* Low-dose computed tomography with lung nodule evaluation (LungRADS1.1, highrisk score group), randomized reporting of coronary artery calcium score and emphysema score<br>|
| Other: Non-reporting group<br>Coronary calcium score and emphysema score are not reported to subjects | Radiation: Low-dose CT screening<br>* Low-dose computed tomography with lung nodule evaluation (LungRADS1.1, highrisk score group), randomized reporting of coronary artery calcium score and emphysema score<br>|
| No Intervention: Low-risk group<br>No CT screening, collection of health data only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint | Positive predictive value (PPV) for lung cancer detection with different inclusion methods (NELSON vs. PLCO) after 2 screening rounds. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary endpoint 1 | Proportion of individuals selected for screening within the high-risk population. | 1 year | 
| Key secondary endpoint 2 | Proportion of lung cancers detected with different inclusion methods (NELSON vs. PLCO) within the overall study population after 5 years. | 5 years | 
| Key secondary endpoint 3 | Proportion of lung cancers detected with in the high-risk population after 5 years. | 5 years | 
| Key secondary endpoint 4 | Specificity within the overall population after 5-year follow-up. | 5 years | 
| Key secondary endpoint 5 | Sensitivity within the overall population after 5-year follow-up. | 5 years | 
| Additional secondary endpoint 1 | Rate of initiation of cardiovascular treatments (in particular lipid-lowering) in the calcium score reporting group vs. the non-reporting group after year 1 of study. | 1 year | 
| Additional secondary endpoint 2 | Efficiency of nodule management algorithms (LungRads1.1 + PanCan) will be evaluated according to the number of patients sorted in the category (a) Next surveillance scan AND the number of patients with lung cancer sorted into category (b) early recall scan, or (c) diagnostic evaluation. | 1 year | 
| Additional secondary endpoint 3.1 | Success of screening program. Based on all individuals enrolled. Definition of success is calculated using Response rate. | 1 year | 
| Additional secondary endpoint 3.2 | Success of screening program. Based on all individuals enrolled. Definition of success is calculated using Reliability of PLCO risk scoring (self-reported vs. on site assessment). | 1 year | 
| Additional secondary endpoint 3.3 | Success of screening program. Based on all individuals enrolled. Definition of success is calculated using Percentage of subjects receiving an adequate low-dose CT scan and report according to DRG guidelines (number of diagnostic CTs/number of all CTs). | 1 year | 
| Additional secondary endpoint 3.4 | Success of screening program. Based on all individuals enrolled. Definition of success is calculated using Percentage of subjects receiving adequate follow-up procedures. | 1 year | 
| Additional secondary endpoint 4.1 | Quality of screening program: CT reading performance (2nd reader vs. CAD vs. AI) | 1 year | 
| Additional secondary endpoint 4.2 | Quality of screening program: Quality of lung nodule management | 1 year | 
| Additional secondary endpoint 4.3 | Quality of screening program: Frequency of detection and management of incidental findings from low dose chest CT (emphysema, coronary heart disease, etc.) | 1 year | 
| Additional secondary endpoint 4.4 | Quality of screening program: LDCT dose management | 1 year | 
| Additional secondary endpoint 5 | Smoking cessation: Success of smoking cessation counseling based on number of participants quitting with or without revealing additional health risks (emphysema score, coronary calcium score or both). | 1 year | 
| Additional secondary endpoint 6.1 | Identification of blood-based biomarkers for early detection of lung tumors: Blood collection and evaluation of various blood-based epigenetic biomarkers in positive LDCT cases with subsequent biopsy on the positive predictive value of the LDCT test. | 1 year | 
| Additional secondary endpoint 6.2 | Identification of exhalation-based biomarkers for early detection of lung tumors: Collection of breath condensate and evaluation of various exhalation-based epigenetic biomarkers in positive LDCT cases with subsequent biopsy on the positive predictive value of the LDCT test. | 1 year | 
| Additional secondary endpoint 7.1 | Cost-effectiveness analysis: Main objectives of the modelling study are to investigate the impact of different components of LDCT lung cancer screening on the long-term all-cause mortality and cost-effectiveness. Key components include risk score-based selection criteria, nodule management protocols, threshold values of imaging biomarkers for cardio-vascular diseases and COPD, and inclusion of smoking cessation programs (performed by Center for Health Economics Research Hannover (CHERH). | 1 year | 
| Additional secondary endpoint 7.2 | Cost-effectiveness analysis: Comparison of patient recruitment strategies: Cost-effectiveness of register-based mailing campaign vs. GP referrals in terms of recruitment of qualified screening subjects (Center for Health Economics Research Hannover - CHERH). | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung cancer, Screening program, Low-dose CT