Short summary

Non-small cell lung cancer has a 5-year survival rate of around 15%. Locoregional disease can be treated with surgery for a better prognosis. However, there is a need for prognostic markers to risk stratify patients and early detection of recurrence. The combination of tumor specific methylated DNA and NK cell activity presents a new prognostic approach to follow-up after curative surgery. This is especially attractive since the markers are available as liquid biopsies.

Rationale

Non-small cell lung cancer has a high incidence all over the Western world. This also applies to Denmark with approximately 4,000 new cases each year. The disease has considerable morbidity and mortality with a 5-year survival rate of around 15%. The association between smoking and lung cancer is very well documented in the current literature. 

Approximately 25% of the patients have extension of the tumor at the time of diagnosis, which allows for operation with curative intent. Despite radical surgery around half of the patients will recur and die within five years. The prognosis depends on the postoperative stage with a 5-year survival rate of 70% in stage IA decreasing to 25% for stage III. Patients in stage pIIA, pIIIA or a T3 tumor are offered four cycles of adjuvant combination chemotherapy with cisplatin and vinorelbine. The treatment improves survival, but the recurrence rate is still high and new prognostic markers are warranted allowing for selection of treatment for different prognostic groups.

Aberrant methylation occurs in almost all malignant tumors, and tumor specific methylated DNA has been suggested for early diagnosis and screening, but so far it has not yet been generally accepted for this purpose. A few papers have circulating methylated DNA to hold independent prognostic information in lung cancer. Most of them included relatively few patients and no subsequent validation. There are no studies dealing with minimal residual disease after the operation, which is the aim of the present study. 

NK cells are anticipated to reflect the general innate immunological measure. NK cell activation holds potential as to screening, but it has not been investigated in relation to minimal residual disease and follow-up. 

Hypothesis

Circulating, methylated DNA in the plasma and NK cell activation persistent after surgery for non-small cell lung cancer holds important prognostic information. 

Objectives

The present study aims at combining the prognostic value of NK cell activation as a host factor and methylated DNA as a tumor specific factor  after surgery for non-small cell lung cancer. The study will also monitor methylated DNA during adjuvant chemotherapy, and investigate the lead time from change in plasma methylated DNA to recurrence. 

Description of the cohort

Adult patients with non-small cell lung cancer eligible for surgery with curative intent. 

Data and biological material

Blood samples. Clinical and demographic data. 

Collaborating researchers and departments

Department of Oncology, Vejle Hospital

• Professor, MD, DMSc, Anders Jakobsen
• Associate professor, MD, PhD, Torben Frøstrup Hansen
• MD, Torben Schjødt Hansen

Department of Medicine, Vejle Hospital

• Professor, MD, DMSc, Ole Hilberg

Department of Clinical Pathology, Vejle Hospital

• Associate professor, MD, PhD, Henrik Hager

Department of Clinical Biochemistry, Vejle Hospital

• Molecular biologist, PhD, Rikke Fredslund Andersen
• Molecular biologist, PhD, Line Nederby