Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases

Inclusion Criteria:

* Patient with a diagnosis of radionecrosis based on a clinical onset of symptoms and radiological findings of RN following radiotherapy, with or without pathological confirmation:

MRI evidence to support the diagnosis of RN (transient increase in irradiated lesion volume -FLAIR hypersignal and/or enhanced portion- without rCBV increase) COMBINED with nuclear medicine imaging:

biphasic 18FDG-PET-TDM/MRI according to Horky or 18F-FDOPA with stage 0-1 according to Lizarraga;

* Symptoms are persistent or worsening despite administration of corticosteroids: at least 1 mg/kg/d of prednisolone or equivalent:

Corticoresistant: neurological symptoms despite administration of at least 2 weeks of 1 mg/kg/d prednisolone or equivalent; Corticodependant: worsening of neurological signs or symptoms after an initial improvement when weaning off steroids at a dose \< 0.5 mg/kg/d prednisolone or equivalent;

* Patients must have received the last cranial irradiation with photons or proton therapy for brain metastases ≥ 3 months with one or more sequences;
* Age≥18-year-old;
* ECOG performance status score ≤ 3
* Life expectancy of at least 3 months assessed by graded prognostic score (DS-GPA) score 0.5 or greater;
* Patient who has never received Bevacizumab for the indication of radionecrosis.
* Adequate organ function:

Bone marrow function

* Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 Platelet Count ≥ 100,000/mm3, Haemoglobin ≥ 10 g/dL (allowing transfusion or other intervention to achieve this minimum haemoglobin) Coagulation
* International normalized ratio (INR) or prothrombin time \< 1.5 × ULN Renal function
* No proteinuria with urine dipstick for proteinuria \> 2+
* Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min (measured or calculated using the CDK-EPI formula) Hepatic Function
* Total bilirubin ≤1.5 x the upper limit of normal (ULN)
* Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN

  * Women of childbearing potential must use effective contraceptive measures during the treatment and for 6 months following its cessation;
  * Signed informed consent;
  * Patient affiliated to a social security scheme.

Exclusion Criteria:

* Evidence of active bleeding or a pathological condition at high risk of bleeding: CNS hemorrhage, bleeding diathesis or coagulopathy, hemoptysis (\>2.5ml of bright red blood per episode), evidence of history of bowel obstruction, abdominal fistula, or gastrointestinal tract perforation or gastro intestinal abscess occurring less than 28 days prior study entry;
* Grade 4 venous thromboelism and peripheral arterial thrombus
* Evidence of very high intracranial pressure that suggests brain hernia and needs emergency surgery;
* Major surgical procedure or significant traumatic injury less than 28 days prior study entry; minor surgery within 3 days prior to initiation of study treatment;
* Clinically significant cardiovascular disease such as uncontrolled arterial hypertension (BP ≥160 mm Hg or diastolic BP ≥100 mm Hg despite maximal medical therapy), cerebrovascular event, myocardial infarction, cardiac arrhythmias, unstable angina, or congestive heart failure within the last 6 months;
* History of hypertensive crisis or hypertensive encephalopathy
* Patients scheduled to undergo head and neck, thoracic, or abdominal radiotherapy during the study treatment
* Prior bevacizumab ≤ 3 months before randomization;
* Progressive brain metastases;
* History of severe allergic anaphylactic reactions to bevacizumab
* Patients with a known hypersensitivity to the active substance or to any of the excipients of bevacizumab are not eligible for participation;
* Patients with a contraindication to the treatment with bevacizumab according to the European SmPC
* Patient pregnant and/or nursing;
* Mental impairment (psychiatric illness/social situations) that may compromise the ability of the patient to give informed consent and comply with the requirements of the study;
* Patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship;
* New cerebral metastasis detected during the inclusion imaging evaluation;
* Prior diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES) with bevacizumab;
* Hypersensitivity known to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.