Summary of findings for the main comparison.

Long‐term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma
Patient or population: people with glioma surviving at least two years Settings: tertiary care
Comparison and Outcomes	Relative effect (95% CI)	No of participants andstudies	Quality of the evidence (GRADE)	Comments
Intervention: radiotherapy Comparison: no adjuvant treatment Outcome: neurocognitive impairment at 5‐ to 6‐year follow‐up	RR 1.38 (0.92 to 2.06)	1 study with data for 195 participants	⊕⊝⊝⊝ very low1,2	Outcome defined as cognitive disability deficits in at least 5 of 18 neuropsychological tests
Intervention: radiotherapy Comparison: no adjuvant treatment Outcome: neurocognitive impairment at 12 year follow‐up	RR 1.95 (1.02 to 3.71)	1 study with data for 65 participants	⊕⊝⊝⊝ very low1,3	Outcome defined as cognitive disability deficits in at least 5 of 18 neuropsychological tests
Intervention: radiotherapy Comparison: no adjuvant treatment Outcome: neurocognitive impairment at 2 year follow‐up	RR 2.50 (0.11 to 56.98)	1 study with data for 31 participants	⊕⊝⊝⊝ very low1,2,3	There was a single event for this outcome in this observational study. The outcome was defined as a significant deterioration (≥ 1 SD) in 8 out of 12 neuropsychological tests
Intervention: radiotherapy Comparison: chemotherapy Outcome: neurocognitive impairment at 3 year follow‐up	RR 1.43 (0.36 to 5.70)	1 study with data for 117 participants	⊕⊕⊝⊝ low2,3	Outcome defined as a MMSE score of 26 or less
Intervention: high‐dose radiotherapy Comparison: low‐dose radiotherapy Outcome: neurocognitive impairment at 2 years after treatment	RR 0.53 (0.06, 4.85)	1 study with data for 65 participants	⊕⊝⊝⊝ very low2,3,4	Outcome defined as decrease in MMSE score from baseline (more than 3 points).There was serious and uneven attrition between groups in this study.
Intervention: high‐dose radiotherapy Comparison: low‐dose radiotherapy Outcome: neurocognitive impairment at 5 years after treatment	RR 0.16 (0.01 to3.20)	1 study with data for 38 participants	⊕⊝⊝⊝ very low2,3,4	Outcome defined as decrease in MMSE score from baseline (more than 3 points). There was serious and uneven attrition between groups in this study.
Intervention: chemoradiotherapy Comparison: radiotherapy Outcome: neurocognitive impairment at 3 years after treatment	RR 0.37 (0.02 to 8.88)	1 study with data for 91 participants	⊕⊕⊝⊝ low2,3	Outcome defined as a decline (of more than 3 points in MMSE score) in cognitive state compared with baseline
Intervention: stereotactic conformal radiotherapy Comparison: radiotherapy Outcome: neurocognitive impairment at 5 years after treatment	RR 4.62 (95% CI 0.25 to 86.72)	1 study with data for 23 participants	⊕⊕⊝⊝ low2,3	Outcome defined as a decline (of more than 3 points in MMSE score) in cognitive state compared with baseline. There was serious sample attrition at 5 years.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.

Abbreviations: SD = standard deviation; MMSE = Mini Mental State Exam

1. Single study contributing data had very serious study design limitations (−2) 2. Uncertain findings; wide 95% CI crossing the line of no effect (−1) 3. Effect estimate based on small sample size (−1) 4. Single study contributing data had study design limitations (−1)