Abstract

Background

This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016.

Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long‐term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on 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 complications following surgery and radiotherapy.

Objectives

To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT.

Search methods

We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022.

Selection criteria

We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing.

Data collection and analysis

We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site‐specific outcomes; and 4. adverse events. Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site‐specific outcomes. We used GRADE to assess certainty of evidence.

Main results

Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN).

HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I² = 0%; 3 RCTs, 166 participants; low‐certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I² = 64%; 5 RCTs, 468 participants; low‐certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I² = 70%; 2 RCTs, 264 participants; low‐certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) −10.72, 95% CI −18.97 to −2.47; I² = 40%; 2 RCTs, 157 participants; moderate‐certainty evidence).

Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high‐certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I² = 0%; 4 RCTs, 357 participants; high‐certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I² = 74%; 2 RCTs, 158 participants; high‐certainty evidence).

Authors' conclusions

These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low‐ to moderate‐certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified.

The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

Author(s)

Zhiliang Caleb Lin, Michael H Bennett, Glen C Hawkins, Charles Paul Azzopardi, John Feldmeier, Robert Smee, Christopher Milross

Abstract

Plain language summary

Hyperbaric oxygen therapy for the treatment of the late effects of radiotherapy

Key message

– In selected people and areas of the body hyperbaric oxygen therapy (HBOT) may help resolve symptoms associated with late radiation tissue injury (LRTI) but further research is required to establish which people may respond and the best timing of such therapy.

What are the problems after radiation treatment and how can it be treated?

There is a risk of serious complications developing in the months and years after radiation treatment (radiotherapy) for cancer. These problems are collectively called LRTI and are due to progressive damage to normal tissue (cells within the body) that has been exposed to radiation. These problems can be very difficult to resolve, and there is some doubt as to the best approaches to treatment. HBOT involves breathing oxygen in a specially designed pressurised chamber. It is used to improve oxygen supply to damaged tissue and support healing.

What did we want to find out?

We wanted to find out if HBOT results in both healing of tissues and the prevention of complications following surgery in an irradiated field and radiotherapy for cancer.

What did we do?

We searched medical databases for clinical studies reporting the evidence for or against the ability of HBOT to improve these complications compared to either no treatment or alternative treatments.

What were the main findings?

There was some evidence that HBOT may improve outcomes in LRTI affecting both bone and soft tissues of the head and neck, the bladder and the lower bowel. There was also some evidence that HBOT may reduce wound breakdown and improve pain following LRTI. HBOT did not affect the risk of dying over the short time that these studies followed their patients. HBOT is generally safe and well‐tolerated, but there is a risk of becoming temporarily short‐sighted from the oxygen exposure and of injury to the ear drum on compression.

What are the limitations of the evidence?

The evidence was mainly limited by small numbers of people and studies, poor reporting of methods and results, and uncertainty as to the exact degree of improvement with HBOT. A study of costs would also be useful.

How up to date is this evidence?

The evidence is current to January 2022.

Author(s)

Zhiliang Caleb Lin, Michael H Bennett, Glen C Hawkins, Charles Paul Azzopardi, John Feldmeier, Robert Smee, Christopher Milross

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

There is low‐ to moderate‐certainty evidence that hyperbaric oxygen therapy (HBOT) improves outcomes in late radiation tissue injury (LRTI) affecting bone and soft tissues of the head and neck and some evidence for improvement in radiation cystitis and proctitis. However, new evidence suggests HBOT may not improve outcomes in osteoradionecrosis or prevent death. There is no evidence of any important clinical effect on neurological tissues, either peripheral or central. Our conclusion remains that the application of HBOT for selected individuals and tissues is justified.

While the small number of studies, modest numbers of participants, and methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation, the pathology of radiation injury suggests many tissues may respond. Further research is required to establish the optimum participant selection and timing of any such therapy. An economic evaluation should also be undertaken.

Implications for research 

Given the new conflicting study results, there is a strong case for further large randomised studies of high methodological rigour in order to define the true extent of benefit from the administration of HBOT for people with LRTI. Specifically, more information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the oxygen dose most appropriate. Any future studies would need to consider in particular:

• appropriate sample sizes with power to detect expected differences generated by this review;
• careful definition and selection of target participants;
• appropriate oxygen dose per treatment session (pressure and time);
• total number of treatment sessions;
• appropriate supportive therapy to which HBOT would be an adjunct;
• use of an effective sham therapy;
• effective and explicit blinding of outcome assessors;
• appropriate outcome measures including all those listed in this review;
• careful elucidation of any adverse events;
• the cost‐utility of the therapy.

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