Short summary

Non-small cell lung cancer has a 5-year survival rate of less than 20%. Locoregional disease can be treated with radiotherapy if surgery is not possible, but there is a need for prognostic markers. The combination of tumor specific methylated DNA, sPD-L1, and NK cell activity represents a new prognostic approach to follow-up after curative radiotherapy. This is especially attractive since all three markers are available as liquid biopsies.

Rationale

Non-small cell lung cancer (NSCLC) has a high incidence in Denmark with approximately 4,600 new cases each year. The disease has considerable morbidity and mortality with a 5-year survival rate of less than 20%.

Patients with locoregional disease are eligible for treatment with curative intent. If surgery is not possible, the patient is offered radiotherapy. Approximately 15% have locoregional disease that allows them to receive radiation with curative intent. Despite progress in radiotherapy, the progression rate remains high resulting in a 2-year progression free survival (PFS) of approximately 50% and a 5-year survival rate of around 20%.

Aberrant methylation occurs in almost all malignant tumors, and tumor specific methylated DNA has been suggested for early diagnosis and screening and may also hold prognostic information. Programmed cell death protein 1 (PD-1) is an immune checkpoint protein expressed on the surface of T lymphocytes, among others. A few studies have suggested soluble PD-L1 (sPD-L1) in plasma as a prognostic marker in NSCLC. Natural killer (NK) cells serve as an innate immunological surveillance factor in the biological defence against cancer. Recent studies have pointed to NK cell activity as a possible prognostic marker.

Objectives

The present study will evaluate the prognostic value of methylated DNA, sPD-L1, and NK cell activity after completed radiotherapy with curative intent. The study will also monitor these biomarkers during follow-up and investigate the lead time from changes to progression or death.

Description of the cohort

Adult patients with non-small cell lung cancer eligible to receive radiotherapy with curative intent.

Data and biological material

Blood samples. Clinical and demographic data from the patient journal.

Collaborating researchers and departments

Department of Oncology, Vejle Hospital

• Professor, MD, DMSc, Anders Jakobsen
• Associate professor, MD, PhD, Torben Frøstrup Hansen
• MD, Christa Haugaard Nyhus
• 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