Stereotactic Radiotherapy in Oligometastatic Brain Disease: a Randomised Phase III Study Comparing Hypofractionated Stereotactic Radiation Therapy (3*10 Gy) to the Historical Single-dose Radiosurgery (1*20 to 25 Gy) With Medico-economic Evaluation.

Inclusion Criteria:

• Patients aged ≥ 18 years

• WHO performance status 0 or 1;

• Patient eligible for SRT after a multidisciplinary committee decision; Patient withBMs from radioresistant cancer (renal cell carcinoma, sarcoma, melanoma) is eligible

• Patient having up to 5 BM of solid tumours with an histologically proven diagnoses;patients who have had a metastasectomy and having 1 to 4 BM lesions is eligible (ANOCEF recommendations); post-operative cavity must be treated by radiosurgeryaccording to local procedures with respect of non-inclusion criteria* (cavity willnot be analyzed for efficacy)

• Presence of at least one and no more than 5 target lesions for SRT, measuringbetween 10 and 25 mm. In the event of synchronous BM, lesions measuring less than 10mm or more than 25mm (1 to 4 lesions) will be treated at the discretion of theinvestigator

• Max cumulative GTV of 30cm3

• Normal complete blood count (CBC)

• Absence of bleeding BM or meningeal carcinomatosis;

• Symptomatic BM are allowed

• DS-GPA score:

• Renal cancer: DS-GPA 2,5 or more

• Breast cancer: DS-GPA 2,5 or more

• Melanoma: DS-GPA 1.5 or more

• Gastro-instestinal (GI) cancer: DSGPA 3 or more

• Adenocarcinoma lung cancer: DS-GPA 2 or more (DS-GPAmol)

• Squamous lung cancer : DS-GPA 2,5 or more (DS-GPAmol)

• For cancers where the DS-GPA score is not applicable, the patient is eligibleif eligibility criteria are met

• Patient with no concomitant systemic treatment; in case of ongoing systemictreatment, wash out period of 3-7 days before and after SRT, depending of drug andat the discretion of investigator;

• Patient sufficiently cooperating to perform the treatment with the use of athermoformed mask;

• Patient whose neuropsychological abilities allow to follow the requirements of theprotocol;

• Female with childbearing potential must use adequate contraception

• Signed informed consent formOligoBM-01 Trial - ID-RCB number: 2021-A01622-39 -version 3.1 dated from 2023-06-22 Page 9 of 51

• Patients affiliated to the social security system

Exclusion Criteria:

• Patients with current or past history small cell lung cancer, germ-cell tumours,lymphoma, leukemia and multiple myeloma within the last 5 years;

• Patients with metastases in the brain stem, or within 1 cm of the optic apparatus;

• Patients with an associated neurodegenerative disease;

• Any symptoms not attributable to BM or cancer disease requiring long termcorticosteroid use (regardless of dose);

• Contraindication to perform the brain MRI or gadolinium or iodinated contrast;

• Known hypersensitivity to the contrast product or to any their excipients

• Patients with previous brain stereotactic irradiation

• Whole brain irradiation history;

• Haemorrhagic metastasis;

• Ongoing anti angiogenic treatment (treatment should be held 3-7 days beforeirradiation and re-initiated 3-7 days after irradiation for patient to be eligible);

• Patients with too close brain lesions for whom a treatment plan on one targetmetastasis delivers a dose > 5 Gy on other concomitant metastasis ;

• Patient deprived of liberty or under guardianship;

• Known pregnancy or breastfeeding

• Any geographical conditions, social and associated psychopathology that maycompromise the patient's ability to participate in the study;

• Participation in a therapeutic trial for less than 30 days.

• Patient deprived of freedom or under guardianship