An open-label phase II study, investigating toxicity, treatment efficacy and the local tumor control rate in 69 patients with centrally located tumors and in 69 patients with ultra-centrally located tumors in the lung. Treatment and patient outcomes will be recorded. Centrally located tumors are treated on standard-linacs with daily CBCT image-guidance and plan adaptation. Ultra-centrally tumors are treated on MR-linacs with daily MR-guided plan-adaptation.

The STRICT-LUNG study will evaluate the feasibility and safety of daily image-guided SBRT in centrally located lung tumors (primary, oligo-metastatic or oligo-progressive). The STAR-LUNG study will evaluate the feasibility and safety of daily adaptive MR-linac based SBRT in ultra-centrally located lung tumors (primary, oligo-metastatic or oligo-progressive).

The tumor is considered central when the tumor is located within 0.5 -2.5 cm in all directions of the PBT or the esophagus. The PBT includes trachea, main bronchi and intermediate bronchus and 5 lobar bronchi. In addition, the tumor is also considered central, if it is located <0.5 cm from the spinal cord, heart and aorta.

Ultra-centrally located tumors are tumors located within the 0.0 to 0.5 cm zone of trachea, main bronchi or intermediate bronchus. The patient will be excluded if the tumor invades the trachea, bronchi, esophagus, or pericardium/heart (radiological or by bronchoscopy assessment).

The main purposes are to evaluate the feasibility, safety and efficacy of stereotactic radiation to centrally and ultra-centrally located tumors, including treatment related adverse events, quality of life (QoL) assessments, local tumor control rate, disease free survival, and overall survival and facilitate future stratification of this patient group for definitive treatment.

Treatment related adverse events (TRAE) will be registered at baseline, end of treatment, 4-6 weeks, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60 months after treatment, and hereafter every year until 10th year of follow-up.

Enrolment in both trial categories may continue until the required numbers in both groups have been reached.

Inclusion Criteria:

• Histology or cytology proven non-hematological cancer or known cancer with local progressive recurrence.
• ECOG performance status ≤ 2.
• Age > 18 years old. • Life expectancy > 6 months.
• Maximum one central tumor with the diameter ≤ 5 cm or > 1 adjacent located tumors with a summarized diameter (measured from the outer margin from one tumor to the outer margin of the other) of maximum 5 cm on a diagnostic CT-scan.
• Medically inoperable or refused surgery.
• The central tumors must be localized within or touching the 2.5 cm-zone of the PBT, or within 0.5 cm from the spinal cord, esophagus or heart. Evaluation is primarily performed on the diagnostic CT scan
• All metastatic sites are treated or planned for ablative therapy (including surgery). For oligo-progressive disease (OPD), only the sites in progression are required to fulfil this criterion
• Adequate lung function to tolerate treatment, at the discretion of the treating physician. • Ability to understand and willingness to sign a written informed consent document. • Patient must be accessible to treatment and follow-up procedures
• Fertile women must have a negative pregnancy test. Fertile men and women must use effective contraception. Fertile women included in the study must use effective contraception for the duration of study treatment and one month thereafter.
• Ultra-centrally located tumors are tumors located within the 0.0 to 0.5 cm zone of the trachea, main bronchi or intermediate bronchus. Evaluation is primarily performed on the diagnostic CT scan
• Patients with other non-central tumors synchronous with the central lesion may be included and treated with SBRT in respect to local practice.
• A baseline PET/CT scan within 2 months of inclusion.
• An ablative strategy should be deemed clinically relevant and it is at the discretion of the treating physician to decide.

Exclusion Criteria:

• Tumor with intra-bronchial or intra-tracheal growth, as assessed on a diagnostic CT/MR-scan or endoscopic procedure
• If the patient has received previous radiotherapy, the combined dose at the radiation site must be evaluated by the treating physician and preferably not exceed the dose constraints
• Patient cannot tolerate the physical set up required for SBRT. • Uncontrolled intercurrent illness
• Pregnancy
• Patient participating in another interventional study
• For patients in STAR-LUNG, lack of MR compatibility due to pacemaker, inserted steel or similar.