The goal of this randomized non-inferiority clinical trial is to investigate whether single-isocenter SBRT using one treatment plan is similarly effective as multiple-isocenter SBRT using multiple treatment plans for multiple extracranial metastases. The main question it aims to answer is:

- whether 1-year freedom from local disease progression at the site of treated metastases after single-isocenter SBRT is non-inferior against multiple-isocenter SBRT at the same prescription doses.

Cancer patients with multiple extracranial distant metastases will be randomly assigned and treated either with single-isocenter SBRT or multiple-isocenter SBRT.

Treatment planning of SBRT for multiple metastases usually employs multiple isocenters, one for each target, resulting in multiple treatment plans. Execution of such treatments requires sequential multiple setups and treatment plan verifications. This practice complicates the workflow of SBRT planning and delivery and makes target-by-target treatment lengthy and patient compliance and comfort suboptimal. The investigators hypothesized that single-isocenter SBRT for extracranial multiple metastases is non-inferior in terms of local efficacy as compared to multiple-isocenter SBRT at the same radiation dose prescription.

Inclusion Criteria:

• Written informed consent according to Swiss law and ICH/GCP regulations signed and dated by the participant and the investigator before any trial specific procedures (Informed Consent Form);

• Distant extracranial metastases (lung, mediastinal/cervical lymph node, liver, bone including spinal/paraspinal and abdominal/pelvic) from histologically confirmed cancer;

• Distant metastases confirmed by imaging:

  • CT is required in all cases;
  • MRI is required for spinal and recommended for liver metastases;
  • PET/CT is recommended for tumors showing high uptake of 18F-FDG, 11Ccholine, 68Ga- or 18F-PSMA;

• At least 2 distant metastases that are amendable to treat with a single isocenter approach according to the judgment of the treating clinician;

• Patients who are willing and able to comply with scheduled visits, treatment, and other trial procedures.

Exclusion Criteria:

• Prior radiotherapy for distant metastases if overlapping previous and current treatment plans leads to excessive dose to OARs;
• Distant metastases with extension into the gastrointestinal tract, skin;
• Large inter-lesion distance and location of distant metastases in different organs with different motion patterns;
• Women who are pregnant or breast feeding;
• Intention to become pregnant during the course of the trial;
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases;
• Known or suspected non-compliance, drug or alcohol abuse;
• Inability to follow the procedures of the trial, e.g. due to language problems of the participant;
• Enrolment of the investigator, his/her family members, employees and other dependent persons.

Female participants who underwent hysterectomy and/or bilateral oophorectomy or postmenopausal for longer than 2 years are not considered as being of child bearing potential.

Upon an individual request