Randomized phase II trial. The study aims to investigate a different and potentially safer radio therapeutic treatment method for brain metastases. The current standard of stereotactic radiotherapy (SRT) in one or three fractions is compared to fractionated stereotactic radiotherapy (fSRT) in five fractions.

Randomized phase II trial. Stereotactic radiotherapy is one of the most frequently chosen treatment options for brain metastases. There are an increasing number of long term survivors. Brain necrosis (e.g. radio necrosis) is the most important long term side effect of the treatment, occurring in up to 40% of patients, dependent on the size of the metastasis and delivered radiotherapy dose. Retrospective studies have shown that the incidence of radio necrosis, as well as local tumor recurrence, can be decreased with a risk difference of around 20% by administrating fractionated stereotactic radiotherapy (fSRT, e.g. five fractions) over single fraction stereotactic radiotherapy, especially in large brain metastases. In this trial, one group is treated with SRT in one or three fractions. The other group is treated with fSRT in five fractions. Survival, toxicity and patient reported quality of life are monitored.

Inclusion Criteria:

• Age ≥ 18 years
• At least one brain metastasis of large cell cancer suitable for SRT
• Karnofsky Performance Status ≥ 70
• Ability to provide written informed consent
• New brain metastases during follow-up after surgery allowed (when outside of resection cavity area)
• New brain metastases during follow-up after previous SRT allowed (when outside of previous irradiation field)

Exclusion Criteria:

• Contra-indication for MRI scan
• Primary tumor of small cell lung cancer, germinoma or lymphoma
• Prior whole brain radiotherapy or SRT on the current target brain metastases (in field re-irradiation)
• Presence of leptomeningeal metastases
• Previous inclusion in the SAFESTEREO study