Wang 2010

Methods	Design: randomised controlled trial Country: 76 institutions in USA and Canada Accrual dates: 1994 to 2002 with long‐term follow‐up Trial reg: Radiation Therapy Oncology Group Trial 9402. NCT 00002569 Funding: Radiotherapy oncology group grants, North Central Cancer Treatment Group Grant, Eastern Cooperative Oncology Group Grant, Southwest Oncology Group Grant, Community Clinical Oncology Program Grant, National Cancer Institute, National Cancer Institute of Canada. Authors state no conflict of interest
Participants	No. randomised: 291 No. analysed: 291. No patients were lost to follow‐up but due to death and other factors the number analysed at different time points decreased over time. Only 29/191 had completed all assessments at 5 years for the assessment of cognitive function (MMSE) Inclusion/exclusion criteria: patients 18 years or more with confirmed diagnoses of anaplastic oligodendroglioma and anaplastic oligoastrocytoma with Karnofsky performance status 60 or more after surgery, adequate marrow and organ function, not pregnant and with no other serious illness. Age: Median age in 'chemotherapy plus radiotherapy' group 43 (range 18 to 75) and in the radiotherapy group median 43 (range 19 to 76). Gender: MF; radiotherapy plus chemotherapy group 90/58; radiotherapy alone 84/59 (approximately 60% male in both groups) Glioma type: anaplastic oligodendroglioma 150/291; anaplastic oligoastrocytoma 141/291. Glioma grade: grade III. 161 had moderately anaplastic disease and 130 highly anaplastic. Resection/biopsy: total resection in the CRT and RT alone groups 40/148 and 53/143; partial resection 85 and 75, biopsy only 21 and 14. Anti‐epileptics/SSRIs: not stated (corticosteroids at baseline CRT group and 79 in the RT group Duration of FU: median survival for surviving patients was 6.9 years (64% had died)
Interventions	Arm 1: (n = 148) chemotherapy and radiotherapy. Chemotherapy within 1 week of randomisation. 4 cycles every 6 weeks before radiotherapy: lomustine 130 mg/m² orally on day 1, procarbazine 75 mg/m² orally daily days 8 to 21 and vincristine 1.4 mg/m² IV on days 8 and 29. There was no 2 mg limit on vincristine. Radiotherapy 59.4 Gy in 33 fractions of 1.8 Gy each 5 days a week. Arm 2: (n = 143) radiotherapy alone as above
Outcomes	Reported review outcomes: Cognitive function MMSE and Quality of life (B‐QOL, Brain Quality of Life,) baseline, 9 and 12 months, 4 monthly in year 2, 6 monthly years 3 to 5 then annually Other reported study outcomes: survival; toxicity and symptoms were assessed but not reported in detail or by randomisation group
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not fully described but was a RTOG trial and randomisation was stratified
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding not feasible and staff and patients would have been aware of randomisation group. It was not clear whether lack of blinding would have affected those outcomes assessed. (It is not clear if those with radiotherapy alone completed treatment before those receiving chemotherapy.)
Blinding of outcome assessment (detection bias) All outcomes	High risk	Detection of survival outcomes are unlikely to have been affected by assignment. Patients completed forms themselves for cognitive function
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	There was considerable loss to follow‐up due to death and disease progression. There was an attempt by the authors to take account of these factors in analysis and analysis was mainly relating to within‐subject factors
Selective reporting (reporting bias)	Unclear risk	Outcomes that may be important to patients were not reported in full (toxicity, nausea, etc). Also much of the analysis was not by randomisation group
Other bias	Unclear risk	None noted

CNS = central nervous system; EORTC = European Organisation for Research and Treatment of Cancer; Gy = Grays; LGG = low grade glioma; HGG = high grade glioma; NR = not reported; HRQoL = Health‐related quality of life; IQ = intelligence quotient; ITT = intention to treat; KPS = Karnofsky Performance Score; MMSE = Mini Mental State Examination; NAT = no adjuvant treatment; NS = not statistically significant; QoL = quality of life; PFS = progression free survival; OS = overall survival; RCT = randomised controlled trial; RT= radiotherapy; RTOG = Radiation Therapy Oncology Group; SD = standard deviation; WHO = World Health Organization