Tang 2014.

Methods	Open‐label, randomised controlled trial
Participants	Adult patients (> 18 years old) treated with radiotherapy at least 6 months prior to study enrolment who have developed radiographic evidence of radionecrosis based on MRI features
Interventions	Edaravone: 30 mg given orally twice daily for 14 days and methylprednisolone 500 mg IV x 3 days followed by prednisone orally on a tapering schedule over 30 days, as tolerated. Methylprednisolone: 500 mg IV x 3 days followed by prednisone orally on a tapering schedule over 30 days, as tolerated.
Outcomes	Total of 154 patients enrolled, of which 137 patients were eligible for analysis: 72 patients in the edaravone plus corticosteroid treatment group versus 65 patients in the corticosteroid group Primary endpoint Radiological response: patients who received edaravone had a greater radiological response with a mean difference (MD) of 3.03 (95% CI 0.14 to 5.92) higher than those who did not receive edaravone. This was observed as a greater reduction in brain oedema by 5.08 + 10.32 cm2 was observed in the edaravone plus corticosteroid group versus 2.05 + 6.71 cm2 in the corticosteroid group (P value = 0.04). Reduction in enhancing lesion volume was also notable in both groups but not significantly greater with the addition of edaravone to corticosteroids compared with corticosteroids alone (P = 0.47). Secondary endpoints Clinical improvement: on LENT/SOMA, patients had a significantly better response with edaravone plus corticosteroids versus corticosteroids (P value = 0.006) such that the RR was 1.59 (95% CI 1.11 to 2.27) Corticosteroid requirement: corticosteroid requirements were not reported. Toxicities: AEs included insomnia, hyperglycaemia, liver dysfunction and epistaxis, but no difference in AEs was observed between treatment arms. Quality of Life: none reported
Notes	1:1 randomisation, N = 154 patients enrolled (77 patients per arm). During the study 17 patients withdrew, 5 in the edaravone group and 12 in the control group of which 5 withdrew because they requested edaravone). A total of 11 patients were lost to follow‐up. The toxicities were mild on edaravone and not significantly greater compared with corticosteroids.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	The method of study arm allocation was not described.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement of ‘Low risk’ or ‘High risk’;
Blinding of outcome assessment (detection bias) All outcomes	High risk	For the primary endpoint of the study of radiological oedema response (primary outcome of the study), the study repots that the neuroradiologists reporting response were blinded to group assignment, but the blinding procedure was not described. For the LENT/SOMA assessment, there is high risk as patients were aware of their treatment group.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were 17 patients who withdrew from the study and another 11 patients who were lost to follow‐up, summing up to 18% attrition. This leaves at least 80% of enrolled patients to be assessed, therefore meeting the predefined criteria of low risk.
Selective reporting (reporting bias)	High risk	One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis
Other bias	Unclear risk	Insufficient information to permit judgement as to whether any other biases may be present

AE: adverse effects
 CCMSE: Cantonese version of the Mini‐Mental Status Examination 
 CI: confidence interval
 HKLLT: Hong Kong List Learning TestHVLT‐R: Hopkins Verbal Learning Test Revised
 IU: international unit
 IV: intravenous
 LENT/SOMA: late effects in normal tissues subjective, objective, management and analytic scales
 MD: mean difference
 MDASI‐BT: M.D. Anderson Symptom Inventory Brain Tumor Module
 MRI: magnetic resonance imaging
 RR: risk ratio