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Cochrane Database of Systematic Reviews

Long‐term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma

Information

DOI:
https://doi.org/10.1002/14651858.CD013047.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 05 August 2019see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:

  1. Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group

Copyright:
  1. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Theresa A Lawrie

    Correspondence to: Cochrane Gynaecological, Neuro‐oncology and Orphan Cancer Group, 1st Floor Education Centre, Royal United Hospital, Bath, UK

    [email protected]

  • David Gillespie

    Department of Neuropsychology, Western General Hospital, Edinburgh, UK

  • Therese Dowswell

    C/o Cochrane Pregnancy and Childbirth Group, Department of Women's and Children's Health, The University of Liverpool, Liverpool, UK

  • Jonathan Evans

    School of Psychological Medicine, University of Glasgow, Glasgow, UK

  • Sara Erridge

    Edinburgh Cancer Centre, NHS Lothian, Edinburgh, UK

  • Luke Vale

    Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK

  • Ashleigh Kernohan

    Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK

  • Robin Grant

    Edinburgh Centre for Neuro‐Oncology (ECNO), Western General Hospital, Edinburgh, UK

Contributions of authors

Theresa Lawrie and Therese Dowswell wrote the first draft of the review. All authors contributed to study screening and data extraction. All authors advised on and approved the final version of the review.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • NIHR 16/144 Cochrane Programme Grant Scheme, UK.

Declarations of interest

Theresa Lawrie: none known
Therese Dowswell: none known
David Gillespie: none known
Jonathan Evans: none known
Sara Erridge: none known
Luke Vale: Member of NIHR Health Technology Assessment Clinical Evaluation and Trials Panel until March 2018
Ashleigh Kernohan: none known
Robin Grant: none known

Acknowledgements

We would like to thank the Information Specialist, Jo Platt, and the Gynaecological, Neuro‐oncology and Orphan Cancer Group (GNOC) Managing Editors, Gail Quinn and Clare Jess, for their advice and support in the preparation of this review. In addition, we would like to thank the library staff at the Royal United Hospital, Bath, UK for sourcing many of the articles cited.

This project was supported by the National Institute for Health Research (NIHR), via Cochrane Programme Grant funding to the Cochrane Gynaecological, Neuro‐oncology and Orphan Cancer Group. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service (NHS) or the Department of Health.

The authors and Cochrane Gynaecological, Neuro‐oncology and Orphan Cancers, are grateful to the following peer reviewers for their time and comments: Helen Bulbeck ‒ brainstrust, UK; Julia Day ‒ Edinburgh Centre for Neuro‐Oncology (ECNO), UK; Michael Hart ‒ Addenbrooke's Hospital, UK; Riccardo Soffietti ‒ Italy.

Version history

Published

Title

Stage

Authors

Version

2019 Aug 05

Long‐term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma

Review

Theresa A Lawrie, David Gillespie, Therese Dowswell, Jonathan Evans, Sara Erridge, Luke Vale, Ashleigh Kernohan, Robin Grant

https://doi.org/10.1002/14651858.CD013047.pub2

2018 Jun 12

Long‐term side effects of radiotherapy, with or without chemotherapy, for glioma

Protocol

Theresa A Lawrie, Jonathan Evans, David Gillespie, Sara Erridge, Luke Vale, Ashleigh Kernohan, Robin Grant

https://doi.org/10.1002/14651858.CD013047

Differences between protocol and review

We moved the Health‐Related Quality of Life (HRQoL) outcome from a secondary outcome in the protocol to a primary outcome in the review. This facilitated the inclusion of Taphoorn 2007, which reported HRQoL but not neurocognitive outcomes.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram (date of search 16/02/18).
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Figure 1

Study flow diagram (date of search 16/02/18).

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Study flow diagram (date of search 9/10/18).
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Figure 2

Study flow diagram (date of search 9/10/18).

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Forest plot of comparison A. Radiotherapy versus no radiotherapy, outcome: Neurocognitive impairment at 2 or more years after treatment. (dichotomous data)
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Figure 4

Forest plot of comparison A. Radiotherapy versus no radiotherapy, outcome: Neurocognitive impairment at 2 or more years after treatment. (dichotomous data)

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comparison A. Radiotherapy versus no radiotherapy, outcome: Neurocognitive impairment at 2 or more years after treatment. (continuous data)
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Figure 5

comparison A. Radiotherapy versus no radiotherapy, outcome: Neurocognitive impairment at 2 or more years after treatment. (continuous data)

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Forest plot of comparison B: High dose versus low dose radiotherapy, outcome: 2.1 Neurocognitive impairment at 2 years or more after treatment.
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Figure 6

Forest plot of comparison B: High dose versus low dose radiotherapy, outcome: 2.1 Neurocognitive impairment at 2 years or more after treatment.

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Forest plot of comparison C: Conventional versus stereotactic conformal radiotherapy, outcome: Neurocognitive impairment at 2 years or more after treatment.
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Figure 7

Forest plot of comparison C: Conventional versus stereotactic conformal radiotherapy, outcome: Neurocognitive impairment at 2 years or more after treatment.

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Forest plot of comparison D: Chemoradiotherapy versus radiotherapy, outcome: Neurocognitive impairment at 2 years or more after treatment.
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Figure 8

Forest plot of comparison D: Chemoradiotherapy versus radiotherapy, outcome: Neurocognitive impairment at 2 years or more after treatment.

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Forest plot of comparison A (exploratory with totals): Radiotherapy versus no radiotherapy, outcome: Neurocognitive impairment at 2 or more years after treatment.
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Figure 9

Forest plot of comparison A (exploratory with totals): Radiotherapy versus no radiotherapy, outcome: Neurocognitive impairment at 2 or more years after treatment.

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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)

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