The hypothesis for this study is that addition of a moderate dose of radiotherapy to the primary tumor and mediastinal nodes after three months of medical treatment could reduce the tumor burden, partly as an abscopal effect, and thereby improving quality of life and possible also prolonging survival for stage IV NSCLC.

Primary objective: To assess whether the addition of radiotherapy to the remaining thoracic tumor burden following standard medical treatment results in a superior quality of life measured with lung cancer symptom scale (LCSS) in patients with stage IV non-small cell lung cancer. The comparison will be made at three months after randomization.

Secondary objectives: Overall survival, progression-free survival, toxicity and longitudinal quality of life measurements.

Design: Multicentre, randomized, phase III trial. Patients will be registered for the study up-front but randomization will be performed after evaluation of response, three months after initiating medical treatment with chemotherapy/ chemo-immunotherapy or immunotherapy. Randomization will be to thoracic radiotherapy or follow-up (1:1).

Inclusion Criteria:

• Histological or cytological confirmed non-small cell lung cancer (NSCLC)
• Stage IV disease
• Previously untreated disease (before first line treatment)
• No symptomatic brain metastases
• Performance status (WHO) 0-2
• FEV1 (forced expiratory volume one second) ≥ 1 L or >40% of predicted
• Written informed consent
• Life expectancy ≥ 12 weeks
• Platelet count ≥ 100,00/mm3
• Hemoglobin ≥ 10 g/dl
• WBC (White blod cells) ≥ 3,000/mm3
• Kidney function allowing chemotherapy
• Patients scheduled for standard platinum based chemotherapy, chemo-immunotherapy or immunotherapy
• Willing and able to comply with study treatment

Exclusion Criteria:

• Requirement for daily supplemental oxygen
• Second primary malignancy within 3 years, except for any of the following which can be included even if diagnosed within the past 3 years: Carcinoma in situ of the cervix, nonmelanoma skin cancer, history of low-grade (Gleason score ≤ 6) localized prostate cancer, definitely treated stage I breast cancer, other malignancy that was diagnosed and definitely treated ≥ 3 years ago with no subsequent evidence of recurrence
• Concurrent severe and/or uncontrolled medical condition, including any of the following:
• Angina pectoris
• Congestive heart failure within the past 3 months, unless LVEF (left ventricular ejection fraction) > 40%
• Myocardial infarction within the past 6 months
• Clinically significant infection
• Psychiatric illness or social situation that would limit compliance with study requirements
• EGFR (epidermal growth factor receptor) mutation or ALK (anaplastic lymphoma kinas) - rearrangement detected