Hyperbaric oxygen therapy for late radiation tissue injury

Michael H Bennett, John Feldmeier, Neil B Hampson, Robert Smee, Christopher Milross

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. To assess the benefits and harms of HBOT for treating or preventing LRTI. 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. Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. 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. 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. 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.