Physician Referral Guide: Hyperbaric Oxygen for Soft Tissue Radiation Necrosis

Assessing the patient before referral

Before referral for elective hyperbaric care, the referring physician should:

• Confirm the radiotherapy history: the treated site, total dose, fractionation if available, and the interval since treatment, which establishes the injury as a delayed radiation effect rather than another process.
• Exclude active or recurrent malignancy in the treatment field. Most Canadian programmes confirm the absence of recurrent disease before committing a patient to a long course, so recent imaging, endoscopy, or biopsy results should accompany the referral.
• Document that conventional therapy has been tried and has failed, since HBOT is reserved for refractory disease.
• Review the medication and chemotherapy history, specifically current or recent bleomycin and current disulfiram, both of which bear on eligibility.
• Screen for chamber-relevant comorbidity: severe COPD with bullous disease, uncontrolled seizures, untreated pneumothorax, uncontrolled hypertension, and claustrophobia.
• Provide a baseline of the target lesion, for example the degree of haematuria, endoscopic findings, or wound dimensions, so response can be measured over the course.

What the evidence supports

The evidence base is strongest for late radiation cystitis and radiation proctitis, where randomised data exist, and is supported by a Cochrane systematic review across radiation tissue injury.

For late radiation cystitis, the reference trial is RICH-ART (Oscarsson et al., Lancet Oncology 2019, 79 patients across five Nordic hospitals), which reported a 10.1-point absolute improvement in the EPIC urinary total score at six to eight months for hyperbaric-treated patients versus standard care (95% CI 2.2 to 18.1; p=0.013), using a protocol of 240 to 250 kPa for 80 to 90 minutes over 30 to 40 sessions.

For radiation proctitis, the evidence is mixed. Clarke et al. (IJROBP 2008, 120 patients) and Sidik et al. (Acta Med Indones 2007, 65 patients) each reported symptom improvement with HBOT, while Glover et al. (HOT2, Lancet Oncology 2016) found no overall benefit for chronic bowel dysfunction. This counter-evidence informs Canadian practice, which reserves HBOT for refractory cases rather than applying it broadly.

The Cochrane review (Bennett 2016, updated Lin and Bennett 2023, 18 trials and 1,071 participants) found evidence that HBOT may improve some outcomes in radiation proctitis, radiation cystitis, and wound healing in irradiated tissue, while noting that the certainty of evidence varies across outcomes and that further trials are needed.

The mechanistic rationale is well established. Radiation injury produces hypoxic, hypovascular, and hypocellular tissue with impaired healing capacity. HBOT at 2.0 to 2.4 ATA raises tissue oxygen tension, and the proposed mechanism is that this stimulates angiogenesis through release of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1), recruits endothelial progenitor cells, and supports collagen synthesis. The resulting improvement in tissue vascularity may persist after a completed course. Available clinical and registry data have not shown an increased risk of cancer recurrence in irradiated cancer survivors who received HBOT, though this evidence is observational.

The Canadian referral pathway

Soft-tissue radiation injury is treated electively at Canadian hospital-based hyperbaric programmes and is covered by provincial health insurance for the recognised indications. These indications are available at hospital programmes across seven provinces (Ontario, Quebec, British Columbia, Alberta, Nova Scotia, Newfoundland and Labrador, and Saskatchewan). Referrals are routed through the patient's oncology, urology, gastroenterology, or surgical team to the regional hospital chamber.

• Ontario: programmes at Toronto General (UHN), Hamilton General, and The Ottawa Hospital.
• British Columbia: Vancouver General Hospital (Leon Judah Blackmore Pavilion), the hospital chamber for the province, covered under MSP.
• Alberta: Misericordia Community Hospital (Edmonton) and Foothills Medical Centre (Calgary), covered by Alberta Health.
• Quebec: RAMQ covers Hopital du Sacre-Coeur de Montreal and Hotel-Dieu de Levis.
• Nova Scotia, Newfoundland and Labrador, and Saskatchewan: regional hospital programmes accept referrals for these indications.
• Provinces and territories without a chamber (Manitoba, New Brunswick, PEI, Yukon, NWT, Nunavut): inter-provincial referral to the nearest programme, coordinated by the patient's oncology or surgical team.

A typical course runs five days a week for 90 minutes per session: roughly 30 to 60 sessions for radiation cystitis or proctitis, and 30 to 40 sessions for soft-tissue radionecrosis (extended toward 60 if the response is incomplete), spanning about 6 to 12 weeks. Further detail on this indication is available on the Canada Hyperbarics delayed radiation injury page.

How to use the research list below

The list contains every delayed radiation injury study in the Canada Hyperbarics database that was published in 2020 or later and has a freely available full-text version, each linked directly to that full text. Paywalled and abstract-only studies are excluded, and retracted studies are removed. This is a reference list, not a set of summaries. Counts and the open-access set refresh each quarter.