Summary of findings for the main comparison. Bevacizumab compared to placebo for the treatment of brain radionecrosis after radiotherapy or radiosurgery.

Bevacizumab compared to placebo for the treatment of brain radionecrosis after radiotherapy or radiosurgery
Patient or population: people previously treated with radiosurgery or fractionated radiotherapy to the brain or head and neck region with a diagnosis of brain radionecrosis based on clinical and radiological criteria Setting: hospital Intervention: bevacizumab Comparison: placebo
Outcomes	Summary	Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
Reduction in oedema (T2 hyperintensity)	Very small sample size so results were reported descriptively. At 6 weeks, all seven (100%) participants on bevacizumab had a reduction in brain oedema by at least 25%, whereas 0/7 participants receiving placebo had this reduction. All participants in the placebo arm had clinical and/or radiological progression.	Not reported due to sparse data	14 (1 RCT)	⊕⊕⊝⊝ LOW 1 2
Reduction in post‐gadolinium enhancement	Very small sample size so results were reported descriptively. Very small sample size so results were reported descriptively. At 6 weeks, all seven (100%) participants on bevacizumab had a reduction in post‐gadolinium enhancement, whereas 0/7 participants receiving placebo had this reduction. All participants in the placebo arm had clinical and/or radiological progression.	Not reported due to sparse data	14 (1 RCT)	⊕⊕⊝⊝ LOW 1 2
Reduction in neurological/clinical symptoms/severity Follow‐up: range 6 weeks to 12 weeks	7 or 7 who received bevacizumab had stable or reduced clinical symptoms versus only 2 of 7 who received placebo. 5 of 7 patients had worsening neurological symptoms at 3.1 to 8.8 weeks after the first dose of placebo. Since there appeared to be no differences in neurocognitive test results in the trial versus cross‐over bevacizumab treated participant combined, all bevacizumab participants were pooled into one group. While the validity of this is questionable, no significant differences in neurocognitive function changes or symptom severity were observed with bevacizumab treatment compared with placebo in any of the analyses	Not reported due to sparse data and validity concerns	14 (1 RCT)	⊕⊝⊝⊝ VERY LOW 1 2 3
Severe adverse events	No Severe adverse events in 7/7 placebo patients. 3/11 patients who received bevacizumab had severe adverse events (although this overlapped with cross‐over patients).		14 (1 RCT)	⊕⊕⊝⊝ LOW 1 2
Quality of life	None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements
Corticosteroid requirements
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹ Downgraded due to small sample size

² Lack of information regarding the randomisation and blinding procedures and overall high risk of bias

3 Concerns over validity of analyses