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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Radiation: Low-dose CT screening

Detailed Description

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:

1. 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.
2. Integration of access to a smoking cessation program.
3. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 12100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jens Vogel-Claussen, Prof. Dr.; Phone Number: +49 511 532 9817; Email: Vogel-Claussen.Jens@mh-hannover.de
• Study Contact Backup: Name: Heiko Hartleb; Phone Number: +49 641 94436 241; Email: heh@alcedis.de

Study Locations

• Germany
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Recruiting
      • Medizinische Hochschule Hannover
      • Contact: Jens Vogel-Claussen, Prof. Dr.; Phone Number: +49 511 532 9817; Email: Vogel-Claussen.Jens@mh-hannover.de
  • Schleswig-Holstein
    • Großhansdorf, Schleswig-Holstein, Germany, 22927
      • Recruiting
      • LungenClinic Grosshansdorf
      • Contact: Martin Reck, Prof. Dr.; Phone Number: +49 4102 601 2101; Email: M.Reck@lungenclinic.de
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Recruiting
      • Universitätsklinikum Schleswig-Holstein
      • Contact: Sabine Bohnet, Dr.; Phone Number: +49 451 500 45003; Email: Sabine.Bohnet@uksh.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female subjects aged 55-79 years
2. Current or former smokers
3. 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).
4. 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:

1. Comorbidity, which would unequivocally contraindicate either screening or treatment if lung cancer is detected.
2. History of chest CT within the past year preceding the invitation.
3. Inability to undergo non-contrast CT (e.g. ≥ 200 kg body weight, inability to lie flat).
4. Pregnancy

5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Collaborators: University Hospital Schleswig-Holstein; German Center for Lung Research; LungenClinic Grosshansdorf
• Investigators: Study Director: Jens Vogel-Claussen, Prof. Dr., Hannover Medical School

Publications and helpful links

Helpful Links

• Study web page (German language)

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2021
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): January 1, 2028

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 28, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Lung cancer; Screening program; Low-dose CT
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: ESR-20-20770

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No