TL;DR: A 2026 review in Ibrain (Richard, Abem & Roy; DOI 10.1002/ibra.70011) catalogues roughly 25 candidate neuroprotective and therapeutic agents for irradiation-induced brain injury. Hyperbaric oxygen therapy (HBOT) appears in the therapeutic group alongside corticosteroids, vitamin E, bevacizumab, and edaravone. Among that group, HBOT is the only intervention that is publicly funded in Canada under a Health Canada-recognised indication, available at all 11 hospital hyperbaric programmes nationally, and supported by the 2023 Cochrane systematic review (18 studies, 1,071 participants) that confirms benefit for late radiation tissue injury. This post summarises the new review’s catalogue and shows how the Canadian pathway compares.

What the 2026 review actually covers

The Richard, Abem & Roy review (PMID 42023248) is a comprehensive synthesis of agents under investigation for cranial-irradiation injury. Cranial radiotherapy, whether delivered for a primary brain tumour, brain metastases, or adjacent head and neck cancer, can damage healthy neighbouring tissue. The injury cascade involves persistent oxidative stress, reduced neurogenesis, neuroinflammation, vascular alterations, and loss of synaptic connectivity. Patients can develop neurocognitive deficits months to years after treatment that meaningfully affect quality of life.

The review groups candidate agents into three categories based on the timing and mechanism of action:

  • Neuroprotective agents (administered before or during radiation to reduce damage): baicalein, troxerutin, epigallocatechin gallate (EGCG), quercetin, melatonin, valproic acid, lithium, neurosteroid progesterone, minocycline.
  • Therapeutic agents (administered after established injury to reduce ongoing damage and support repair): glucocorticoids, methylphenidate, vitamin E, bisdemethoxycurcumin, phosphodiesterase inhibitors, edaravone, pioglitazone, fenofibrate, glutamate antagonists, human urinary kallidinogenase, bevacizumab, and hyperbaric oxygen therapy.
  • Combined neuroprotective and therapeutic: angiotensin-converting enzyme inhibitors, 3-N-butylphthalide, stem cell therapy, sphingosine-1-phosphate, gangliosides, neurotrophins.

The shared mechanism that runs through almost every agent is reduction of chronic oxidative stress, modulation of inflammation, reduction of cerebral oedema, and dampening of microglia activation. Different agents intervene at different points in that cascade.

Why HBOT stands out clinically in the Canadian context

Listing HBOT alongside roughly two dozen other candidate agents understates how differently positioned it is for a Canadian patient today. Most agents in the review remain investigational, with evidence drawn predominantly from preclinical animal models, in vitro work, or small early-phase trials. By contrast, HBOT for late radiation tissue injury (which includes radiation-induced brain injury) is one of the 14 conditions that Health Canada recognises as an accepted indication for hyperbaric oxygen therapy, and it is publicly funded with a physician referral at all 11 hospital hyperbaric programmes across seven provinces.

The clinical evidence supporting HBOT for late radiation tissue injury is also substantially stronger than for most of the agents in the review. The most-cited reference point is the 2023 Cochrane Database of Systematic Reviews meta-analysis (Lin et al.; 18 studies, 1,071 participants) which found that HBOT may result in complete resolution or significant improvement of late radiation tissue injury affecting the head, neck, bladder, and rectum. For brain-specific outcomes, smaller controlled studies and case series have demonstrated reduction in radiation necrosis volume on MRI, improvement in neurological symptoms, and reduction in steroid dependency.

How HBOT compares to the other “therapeutic” agents in the review

Within the therapeutic group specifically, three of the most clinically established alternatives are worth contrasting with HBOT. The table below summarises each option as it stands in current Canadian neuro-oncology practice.

Agent Canadian access Typical role in radiation brain injury Key trade-off
Corticosteroids (dexamethasone) First-line, publicly funded everywhere Acute symptomatic control of oedema Steroid-dependency, hyperglycaemia, immunosuppression on chronic use
Bevacizumab (anti-VEGF) Through neuro-oncology, funded for eligible cancer indications Steroid-refractory radiation necrosis, MRI lesion reduction Hypertension, proteinuria, thromboembolism, impaired wound healing
Hyperbaric oxygen therapy Health Canada-recognised indication, publicly funded at 11 hospital programmes in 7 provinces Steroid-sparing, late or progressive injury, surgical-bed preparation Daily 60-90 min sessions over 4-8 weeks; standard HBOT contraindications apply
Vitamin E + pentoxifylline (PENTOCLO) Off-label, low-cost, prescribed at clinician discretion Late soft tissue and bone radiation injury Slow time-to-response; brain-specific evidence is limited
Edaravone, pioglitazone, methylphenidate, others Not approved or funded for radiation brain injury in Canada Investigational; small-trial signals only Insufficient evidence for routine use

Glucocorticoids (corticosteroids)

Dexamethasone and other corticosteroids are the standard first-line response to symptomatic radiation necrosis in Canadian neuro-oncology practice. They reduce cerebral oedema and provide rapid symptomatic relief. The trade-off is well known: chronic steroid use carries hyperglycaemia, immunosuppression, myopathy, and other systemic risks, and many patients become steroid-dependent without the underlying tissue damage actually resolving. HBOT is often considered when patients cannot be weaned off steroids, when symptoms persist despite steroid therapy, or when the radiation necrosis is progressive on imaging.

Bevacizumab

Anti-VEGF therapy with bevacizumab has become an important alternative for radiation necrosis that does not respond to corticosteroids. Several controlled studies have shown reduction in MRI lesion volume and improvement in neurological symptoms. Bevacizumab is generally accessed through neuro-oncology and is funded through cancer-care programmes for eligible indications. Side effects can include hypertension, proteinuria, thromboembolism, and impaired wound healing. HBOT and bevacizumab are not mutually exclusive; some patients receive sequential or combined therapy depending on response and clinical context.

Vitamin E

The pentoxifylline plus vitamin E (PENTOCLO) protocol has support from observational studies for late radiation tissue injury, including bone and soft tissue injury after head and neck radiotherapy. Evidence specifically for radiation-induced brain injury is more limited. PENTOCLO is generally well tolerated and inexpensive, but the time-to-response can be slow and the magnitude of benefit varies considerably between patients.

Edaravone, pioglitazone, methylphenidate, and others

Edaravone (a free radical scavenger approved in Japan and South Korea for stroke) is being studied for radiation injury but is not approved for that indication in Canada. Pioglitazone and fenofibrate (PPAR agonists) and methylphenidate (a stimulant studied for radiation-related cognitive symptoms) all have early supportive data but are off-label for radiation brain injury and are not funded for that purpose. The remaining agents in the review’s therapeutic group are largely preclinical at this stage.

Where HBOT does not fit

It is worth being explicit about what HBOT is not. HBOT does not treat or cure the underlying brain tumour. It is not a radiosensitiser available outside of clinical trials in Canada (although Japanese centres including Kohshi and others have explored that off-label application; see the glioblastoma deep-dive for context). And HBOT is not a substitute for steroids in the acute management of symptomatic oedema; it is generally introduced after the initial steroid response and is most useful when steroid dependency or progressive injury becomes the limiting factor.

HBOT is also not appropriate for every patient. Standard contraindications include untreated pneumothorax (absolute), severe COPD with air trapping (relative), recent ear or sinus surgery, certain chemotherapies, and significant claustrophobia. The patient must be medically stable enough for daily 60- to 90-minute sessions, often delivered five days per week for 30 to 40 sessions, with extension if surgical intervention is planned.

How does a Canadian patient access HBOT for radiation brain injury?

The referral pathway runs through neuro-oncology, radiation oncology, or neurosurgery. The treating physician sends a referral to one of the 11 hospital hyperbaric programmes:

  • Ontario: Toronto General Hospital / UHN, Hamilton General Hospital, The Ottawa Hospital
  • Quebec: Hôtel-Dieu de Lévis (the largest 18-person multiplace chamber in Canada), Hôpital du Sacré-Cœur de Montréal
  • British Columbia: Vancouver General Hospital (Leon Judah Blackmore Pavilion)
  • Alberta: Misericordia Community Hospital (Edmonton), Foothills Medical Centre / Arthur J.E. Child Comprehensive Cancer Centre (Calgary)
  • Nova Scotia: QEII Health Sciences Centre (Halifax)
  • Newfoundland and Labrador: Health Sciences Centre (St. John’s)
  • Saskatchewan: Dr. F.H. Wigmore Regional Hospital (Moose Jaw, currently on a reduced schedule following the 2021 disruption)

Patients in the six provinces and territories without an in-province hospital programme (Manitoba, New Brunswick, Prince Edward Island, Yukon, Northwest Territories, Nunavut) are coordinated to the nearest receiving programme through their physician and the relevant interprovincial referral process. See the coverage comparison page for province-by-province billing and wait-time details.

How should a referring physician interpret the new review?

For the typical Canadian patient with confirmed late radiation tissue injury affecting the brain, the practical implication is unchanged: corticosteroids remain the first response, bevacizumab is a strong option for steroid-refractory cases through neuro-oncology, and HBOT is a publicly funded recognised indication with established multicentre clinical experience. The agents that are newer to the literature (edaravone, pioglitazone, several of the natural products) remain investigational and are not commonly part of standard Canadian neuro-oncology practice.

The review’s value for clinicians is in mapping the wider experimental landscape and identifying agents that may become more relevant in the coming years as larger trials report. For patients and caregivers asking about “alternative” treatments after radiation, the review provides a useful framework: most of the agents listed are not yet ready for routine clinical use, while a small number, including HBOT, are well established within their indication boundaries.

What if I am being treated outside Canada?

The review draws on international literature, and most of the candidate agents are being investigated in trials based in Asia, Europe, and the United States. Standards of care for radiation necrosis vary by country. Patients receiving care in the United States may have access to bevacizumab through cancer-care insurance, while patients in Japan may have access to edaravone for off-label indications. The Canadian access pathway described above is specific to the Canadian provincial health insurance context.

Frequently asked questions

Is HBOT covered for radiation brain injury in Canada?

Yes. Late radiation tissue injury (which includes radiation-induced brain injury) is one of the 14 conditions that Health Canada recognises as an accepted indication for hyperbaric oxygen therapy. Treatment is publicly funded at all 11 hospital hyperbaric programmes across seven provinces, with a physician referral from neuro-oncology, radiation oncology, or neurosurgery. Patients in provinces without an in-province programme are coordinated to the nearest receiving hospital through their treating physician. Use the Canada Hyperbarics facilities directory to locate the nearest programme.

How does HBOT compare to bevacizumab for radiation necrosis?

HBOT and bevacizumab are not mutually exclusive. Both have shown reduction in MRI lesion volume and improvement in neurological symptoms in steroid-refractory radiation necrosis. Bevacizumab is generally accessed through neuro-oncology under cancer-care funding; HBOT is publicly funded under provincial health plans as a Health Canada-recognised indication. Some patients receive sequential or combined therapy depending on response, side-effect profile, and the size and location of the necrosis. The choice is typically made by the treating multidisciplinary team after weighing each option’s trade-offs (see the comparison table above).

How many HBOT sessions are needed for radiation brain injury?

A typical course is 30 to 40 daily sessions at 2.0 to 2.4 ATA, each lasting 60 to 90 minutes (some radiation-injury protocols extend up to 120 minutes), delivered five days per week. Additional sessions may be added if surgical resection or reconstruction of the affected tissue is planned. Many patients begin to notice symptom improvement in the second half of the course; the full response is evaluated after the course completes and on follow-up MRI.

Can HBOT be combined with corticosteroids?

Yes, and that is the most common Canadian sequence. Corticosteroids provide rapid symptomatic relief in the acute phase. HBOT is typically introduced when the patient becomes steroid-dependent, when symptoms persist despite ongoing steroid therapy, or when the radiation necrosis is progressive on imaging. The goal is often to reduce or eliminate chronic steroid exposure while addressing the underlying tissue ischaemia.

Are the natural compounds in the review (baicalein, melatonin, EGCG, quercetin) used in Canadian practice?

Not as standard treatment for radiation brain injury. The natural compounds listed in the review are predominantly supported by preclinical animal-model evidence and small early-phase trials. They are not part of standard Canadian neuro-oncology protocols and are not funded for this indication. Patients interested in supplemental approaches should discuss with their treating team to avoid interactions with concurrent radiotherapy, chemotherapy, or other recovery-phase medications.

Where can I see the full Canadian coverage breakdown?

The HBOT Coverage Comparison Across Canada table summarises insurance plan, hospital programme count, private clinics, billing codes, and wait times for all 13 provinces and territories. The province-specific pages (linked from the comparison table) cover referral pathway, emergency access, and out-of-province routing for your specific jurisdiction.

Where this fits with our other coverage

References

  • Richard S, Abem V, Roy S. Potential neuroprotective and therapeutic agents and their mechanisms for irradiation-induced brain injury. Ibrain. 2026. DOI: 10.1002/ibra.70011 (PMID 42023248).
  • Lin ZC, Bennett MH, Hawkins GC, et al. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database of Systematic Reviews. 2023; CD005005.pub5 (PMID 37585677). (18 studies, 1,071 participants).
  • Health Canada. Hyperbaric oxygen therapy. canada.ca
  • Kohshi K, et al. Effects of hyperbaric oxygen on radiation-induced brain injury and on adjuvant therapy for malignant glioma. PMID 17120158; PMID 8898978.

This article summarises a recent review and is intended for informational purposes only. It is not medical advice and should not replace consultation with your healthcare provider. Decisions about radiation injury management should be made with your treating neuro-oncology, radiation oncology, or hyperbaric medicine team.