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Meta-Analysis
. 2016 Apr 28;4(4):CD005005.
doi: 10.1002/14651858.CD005005.pub4.

Hyperbaric oxygen therapy for late radiation tissue injury

Michael H Bennett  1 , John Feldmeier, Neil B Hampson, Robert Smee, Christopher Milross
Affiliations
Meta-Analysis

Hyperbaric oxygen therapy for late radiation tissue injury

Michael H Bennett et al. Cochrane Database Syst Rev. .

Update in

  • Hyperbaric oxygen therapy for late radiation tissue injury.
    Lin ZC, Bennett MH, Hawkins GC, Azzopardi CP, Feldmeier J, Smee R, Milross C. Lin ZC, et al. Cochrane Database Syst Rev. 2023 Aug 15;8(8):CD005005. doi: 10.1002/14651858.CD005005.pub5. Cochrane Database Syst Rev. 2023. PMID: 37585677 Free PMC article.

Abstract

Background: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery.

Objectives: To assess the benefits and harms of HBOT for treating or preventing LRTI.

Search methods: We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11), MEDLINE, EMBASE, DORCTIHM and reference lists of articles in December 2015. We also searched for ongoing trials at clinicaltrials.gov.

Selection criteria: Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing.

Data collection and analysis: Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials.

Main results: Fourteen trials contributed to this review (753 participants). There was some moderate quality evidence that HBOT was more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P value = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5; 246 participants, 3 studies). There was also moderate quality evidence of a significantly improved chance of wound breakdown without HBOT following operative treatment for ORN (RR 4.2; 95% CI 1.1 to 16.8, P value = 0.04, NNTB 4; 264 participants, 2 studies). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P value = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P value = 0.0002, NNTB 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P value = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P value = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no randomised data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse events.

Authors' conclusions: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.

PubMed Disclaimer

Conflict of interest statement

None known. Bennett and Hampson are hyperbaric physicians who regularly treat people with LRTI, while Feldmeier has previous hyperbaric experience. Milross, Feldmeier and Smee are radiation oncologists who refer people with LRTI for HBOT.

Figures

1
1
Study flow diagram.
2
2
Summary of risk of bias in eight domains in the included studies
3
3
Forest plot of comparison: 2 Complete resolution of problem, outcome: 2.1 Complete resolution of clinical problem at end of therapy to three months.
4
4
Forest plot of comparison: 8 Osteoradionecrosis, outcome: 8.1 Complete mucosal cover.
5
5
Forest plot of comparison: 11 Head and Neck, outcome: 11.1 Wound dehiscence.
1.1
1.1. Analysis
Comparison 1 Death, Outcome 1 Death at 1 year.
2.1
2.1. Analysis
Comparison 2 Complete resolution of problem, Outcome 1 Resolution of clinical problem at 1 year.
2.2
2.2. Analysis
Comparison 2 Complete resolution of problem, Outcome 2 Development of osteoradionecrosis following dental implant.
3.1
3.1. Analysis
Comparison 3 Complete resolution or significant improvement of problem, Outcome 1 Complete or significant improvement.
3.2
3.2. Analysis
Comparison 3 Complete resolution or significant improvement of problem, Outcome 2 Sensitivity analysis for missing data in proctitis ‐ best case.
3.3
3.3. Analysis
Comparison 3 Complete resolution or significant improvement of problem, Outcome 3 Sensitivity analysis for missing data proctitis ‐ worst case.
4.1
4.1. Analysis
Comparison 4 Improvement in mean LENT‐SOMA score, Outcome 1 Mean LENT‐SOMA score at 3 months.
5.1
5.1. Analysis
Comparison 5 Resolution of pain, Outcome 1 Pain score change at end of treatment.
5.2
5.2. Analysis
Comparison 5 Resolution of pain, Outcome 2 Pain score change at 12 months.
5.3
5.3. Analysis
Comparison 5 Resolution of pain, Outcome 3 Pain score change at 18 months.
6.1
6.1. Analysis
Comparison 6 Resolution of swelling, Outcome 1 Improvement of lymphoedema.
6.2
6.2. Analysis
Comparison 6 Resolution of swelling, Outcome 2 Relative reduction in arm volume (affected vs. non‐affected).
6.3
6.3. Analysis
Comparison 6 Resolution of swelling, Outcome 3 Proportion with more than 8% reduction in arm volume.
7.1
7.1. Analysis
Comparison 7 Quality of life and functional outcomes, Outcome 1 SF‐36 general health at 1 year.
7.2
7.2. Analysis
Comparison 7 Quality of life and functional outcomes, Outcome 2 Physical functioning score at 1 year.
7.3
7.3. Analysis
Comparison 7 Quality of life and functional outcomes, Outcome 3 Improvements in mean bowel bother score.
7.4
7.4. Analysis
Comparison 7 Quality of life and functional outcomes, Outcome 4 Lymphoedema score at 12 months.
7.5
7.5. Analysis
Comparison 7 Quality of life and functional outcomes, Outcome 5 Quality of life (EORTC Head and Neck Module) at 12 months.
7.6
7.6. Analysis
Comparison 7 Quality of life and functional outcomes, Outcome 6 Quality of Life (EORTC Head and Neck Module) at 12 months.
8.1
8.1. Analysis
Comparison 8 Osteoradionecrosis, Outcome 1 Complete mucosal cover.
8.2
8.2. Analysis
Comparison 8 Osteoradionecrosis, Outcome 2 Establishment of bony continuity.
8.4
8.4. Analysis
Comparison 8 Osteoradionecrosis, Outcome 4 Successful healing of tooth sockets after tooth extraction.
8.5
8.5. Analysis
Comparison 8 Osteoradionecrosis, Outcome 5 Bone loss around implant site.
9.1
9.1. Analysis
Comparison 9 Head and neck soft tissues, Outcome 1 Wound dehiscence.
9.2
9.2. Analysis
Comparison 9 Head and neck soft tissues, Outcome 2 Loss of dental implant.
10.1
10.1. Analysis
Comparison 10 Urinary bladder, Outcome 1 Complete resolution of clinical problem.
10.3
10.3. Analysis
Comparison 10 Urinary bladder, Outcome 3 Daily voiding frequency change at 18 months.
13.1
13.1. Analysis
Comparison 13 Neurological tissue, Outcome 1 Warm sensory threshold 1 week after treatment (°C change from baseline).
13.2
13.2. Analysis
Comparison 13 Neurological tissue, Outcome 2 Warm sensory threshold at 1 year.
13.3
13.3. Analysis
Comparison 13 Neurological tissue, Outcome 3 Net number of significantly improved neuropsychological tests at 3 months (25 tests total).
13.4
13.4. Analysis
Comparison 13 Neurological tissue, Outcome 4 Net number of significantly improved neuropsychiatric tests at 6 months.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Carl 2001 {published data only}
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References to ongoing studies

Forner 2011 {unpublished data only}
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Gesell 2004 {unpublished data only}
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HOPON 2011 {published data only}
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Kuhnt 2008 {unpublished data only}
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NCT01606644 {unpublished data only}
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NCT01822405 {published data only}
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NCT02425215 {published data only}
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NCT02450305 {unpublished data only}
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NCT02714465 {unpublished data only}
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NCT03144206 {unpublished data only}
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Yarnold 2010 {unpublished data only}
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