Late Radiation Tissue Injury (LRTI)
Radiotherapy is an important treatment for many cancers. Modern radiotherapy techniques are much more precise than they were in the past, helping to reduce damage to healthy tissues. However, some healthy tissue near the treatment area can still be affected.
While many people are familiar with the short-term side effects of radiotherapy, some effects can develop months or even years later. These are known as late radiation tissue injuries (LRTI).
Radiotherapy can cause changes in small blood vessels and the body's healing mechanisms. Over time, affected tissues may receive less oxygen and blood supply, making them more vulnerable to pain, breakdown, poor healing, or tissue death (radionecrosis).
Different parts of the body can be affected, including:
- Bone
- Skin and soft tissues
- Bladder
- Bowel
- Head and neck tissues
How can Hyperbaric Oxygen Therapy (HBOT) help?
HBOT involves breathing oxygen inside a pressurised chamber. This increases the amount of oxygen carried in the blood and delivered to damaged tissues.
HBOT cannot restore tissue that has already died. However, it may help by:
- Encouraging the growth of new small blood vessels
- Improving oxygen delivery to damaged tissue
- Supporting the body's natural healing processes
- Reducing symptoms in some people with radiation-related injuries
Research suggests HBOT may benefit selected patients with radiation injuries affecting the pelvis, head and neck, skin, and other soft tissues. As with any treatment, results vary between individuals.
Head and Neck Cancer Treatment
Osteoradionecrosis (ORN) of the Jaw
Some people receiving radiotherapy for cancers of the mouth, tongue, tonsils or throat may later develop problems affecting the jawbone (mandible).
Radiotherapy can reduce blood supply to the bone and surrounding tissues. At the same time, reduced saliva production can affect dental health and increase the need for dental treatment.
In some cases, dental extractions or other procedures may trigger poor healing of the jawbone, leading to a condition called osteoradionecrosis (ORN).
Symptoms can include:
- Exposed bone in the mouth
- Pain
- Infection
- Difficulty chewing
- Poor wound healing
- Occasionally, weakening or fracture of the jaw
Treatment depends on the severity of the condition and may include dental care, medication, surgery, and sometimes HBOT.
HBOT may be recommended in selected patients, particularly when significant surgery is planned or where healing has been impaired by previous radiotherapy.
A typical course may involve:
- 20-30 sessions before surgery or dental treatment
- A further 10 sessions afterwards
Your specialist team will advise whether HBOT is appropriate in your situation.
Pelvic Radiation Injury
Radiotherapy used to treat cancers such as prostate, cervical, bladder, anal, or rectal cancer can sometimes affect nearby organs within the pelvis.
Problems may develop months or years after treatment.
Radiation Cystitis
Radiation cystitis affects the bladder and can cause:
- Blood in the urine
- Increased frequency of urination
- Urgency
- Pain or discomfort when passing urine
- Disturbed sleep due to needing to pass urine frequently
Radiation Proctitis
Radiation proctitis affects the rectum and may cause:
- Rectal bleeding
- Pain
- Diarrhoea
- Mucus discharge
- Urgency
- Incontinence
These symptoms can have a significant impact on day-to-day life and, in some cases, may require hospital treatment.
Research has shown that HBOT can improve symptoms for many patients with radiation cystitis and radiation proctitis, particularly when standard treatments have not provided adequate relief.
A typical course of treatment consists of:
- 40 HBOT sessions
- One treatment per day
- Five days per week
Your treating team will discuss the likely benefits and limitations of treatment in your individual circumstances.
Other Late Radiation Tissue Injuries
Radiotherapy can affect almost any tissue in the body. Although the strongest evidence for hyperbaric oxygen therapy (HBOT) relates to injuries affecting the bladder, bowel, head and neck, and soft tissues, some patients experience less common late effects of radiotherapy.
These may include:
- Soft tissue damage in the head and neck
- Non-healing wounds in previously irradiated areas
- Radiation-related nerve injury (including brachial plexopathy)
- Radiation-related damage affecting the spinal cord (radiation myelopathy)
- Radiation-related injury affecting the eyes or optic nerves
- Persistent pain or fibrosis in previously irradiated tissues
Because these conditions are uncommon, there have been fewer research studies than for other radiation injuries. Treatment decisions are therefore often based on a combination of published evidence, specialist experience, and individual patient circumstances.
In selected cases, HBOT may be considered when symptoms are significantly affecting quality of life and conventional treatments have been unsuccessful.
If you have been diagnosed with a late radiation tissue injury that is not described on this page, please contact us or ask your specialist whether a referral for HBOT assessment may be appropriate.
Late Radiation Tissue Injury (LRTI)
Late radiation tissue injury (LRTI) is one of the most common indications for hyperbaric oxygen therapy (HBOT) worldwide. Symptoms may develop months to years after radiotherapy and are sometimes precipitated or exacerbated by subsequent surgery, trauma, infection, or other insults to previously irradiated tissues.
The underlying pathology is characterised by progressive fibrosis, vascular damage (obliterative endarteritis), reduced cellularity, and impaired tissue perfusion. As a result, irradiated tissues become chronically hypoxic and may progress to non-healing wounds, necrosis, or impaired function. Capillary density can be reduced to as little as 20–40% of normal tissue levels.
HBOT is thought to support tissue recovery through several complementary mechanisms, including:
- Promotion of angiogenesis and neovascularisation, leading to improved tissue oxygen delivery (Marx et al., 1990)
- Modulation of radiation-induced fibrosis (Feldmeier et al., 1998)
- Mobilisation of endothelial progenitor and stem cells involved in tissue repair (Thom et al., 2006; Goldstein et al., 2006)
By increasing dissolved oxygen delivery to hypoxic tissues, HBOT may help support repair processes and improve healing in selected patients with chronic radiation injury.
Evidence Base
The most comprehensive review of the evidence is the 2023 Cochrane Review by Lin et al., which evaluated 18 studies involving 1,071 participants treated for a range of late radiation tissue injuries.
The review concluded that HBOT may improve outcomes in selected patients, particularly those with radiation injury affecting tissues of the head and neck or pelvis. However, the certainty of evidence varied between indications, and the authors emphasised the need for additional high-quality randomised controlled trials to better define patient selection criteria and optimal treatment protocols.
Reference
- Lin ZC, Bennett MH, Hawkins GC, et al. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2023;8:CD005005.
Mandibular Osteoradionecrosis (ORN)
Mandibular osteoradionecrosis remains one of the most widely recognised radiation-related indications for HBOT.
Historically, HBOT formed a central component of treatment following the protocol described by Marx. However, the role of HBOT in ORN has become increasingly debated in recent years as radiotherapy techniques have improved, incidence rates have fallen, and alternative management approaches have emerged, including pentoxifylline/tocopherol-based therapies and advances in reconstructive surgery.
Most patients with early-stage ORN can be managed conservatively. HBOT may be considered in selected patients with progressive disease, associated soft tissue necrosis, poor wound healing, or when extensive surgery is planned.
Marx Staging Protocol
Stage 1
Pathology
- Exposed irradiated bone without features of advanced disease
Management
- Conservative measures and minor debridement
HBOT Protocol
- 30 pre-operative sessions
- 10 post-operative sessions
Stage 2
Pathology
- Stage 1 disease showing limited improvement or requiring more extensive intervention
Management
- Further debridement or limited surgical intervention
HBOT Protocol
- 30 pre-operative sessions
- 10 post-operative sessions
Stage 3
Pathology
- Persistent Stage 1 or 2 disease
- Pathological fracture
- Orocutaneous fistula
- Extensive mandibular involvement extending to the inferior border
Management
- Major resection and reconstructive surgery
HBOT Protocol
- 30 pre-operative sessions
- 10 post-operative sessions
- Additional 10 treatments following definitive surgery
Recent Evidence
HOPON Trial (2019)
The Hyperbaric Oxygen for the Prevention of Osteoradionecrosis (HOPON) trial assessed whether HBOT reduces the risk of ORN following dental extractions in previously irradiated patients.
The study did not demonstrate a significant reduction in ORN incidence with prophylactic HBOT. Interpretation was complicated by the unexpectedly low incidence of ORN in both treatment groups, reflecting improvements in modern radiotherapy and dental care.
DAHANCA-21 (2022)
The DAHANCA-21 study evaluated HBOT as an adjunct to surgery for established ORN.
Although patients receiving HBOT demonstrated numerically better outcomes and improvements in symptoms such as xerostomia, dysphagia and salivary function, the study was underpowered and differences did not reach statistical significance. The findings suggest potential benefit but highlight the need for larger studies.
Breast and Chest Wall Radiation Injury
Several observational studies have reported improvements in pain, fibrosis and soft tissue symptoms following HBOT for breast cancer-related LRTI.
Carl et al. (2001) evaluated 44 patients and reported significant reductions in SOMA-LENT scores, with complete symptom resolution in seven individuals.
Teguh et al. (2016) followed 57 patients with breast radiation injury and demonstrated reductions in:
- Arm and shoulder pain (46% to 17%)
- Breast pain (67% to 15%)
- Hypersensitivity (54% to 15%)
The authors reported substantial overall symptom improvement following HBOT, although larger controlled studies are still required.
Case series have also described successful management of radiation-induced chest wall and soft tissue necrosis.
Radiation-Induced Skin Necrosis
Available observational studies and case series suggest that HBOT may improve healing in selected patients with radiation-induced skin necrosis.
Feldmeier et al. reported complete resolution in 11 of 17 patients treated with HBOT. When patients with recurrent tumour were excluded, the reported response rate increased further.
A prospective observational study of 411 patients conducted at Virginia Mason Medical Center demonstrated high rates of clinical improvement across a range of chronic radiation injuries treated with HBOT (Hampson et al., 2012).
A systematic review involving 720 patients concluded that HBOT appears to be a safe and potentially effective treatment option for radiation-induced skin necrosis, although the overall quality of evidence remains limited by the predominance of non-randomised studies (Borab et al., 2016).
Radiation Cystitis
Radiation-induced cystitis is a recognised late complication of pelvic radiotherapy, affecting approximately 5–10% of patients receiving treatment for pelvic malignancies.
Symptoms may include:
- Haematuria
- Frequency and urgency
- Nocturia
- Dysuria
- Reduced quality of life
The UHMS review of published case series reported clinical improvement in most treated patients, with approximately 76% achieving either partial or complete symptom resolution.
More recent evidence has strengthened the evidence base.
A multicentre registry study by Moses et al. (2024) demonstrated significant improvements in patient-reported urinary symptoms, haematuria and quality-of-life measures following HBOT.
Long-term follow-up of the RICH-ART study (Oscarsson et al., 2025) demonstrated sustained symptom improvement over five years. Approximately 69% of patients who responded at six months maintained their improvement throughout follow-up, while some initially non-responsive patients also experienced later clinically meaningful benefit.
Radiation Proctitis
Radiation proctitis can significantly affect quality of life and may cause rectal bleeding, pain, urgency and altered bowel function.
The UHMS review identified favourable outcomes across multiple case series involving nearly 200 patients with radiation-induced proctitis, enteritis or colitis, with most patients demonstrating at least partial improvement.
The strongest evidence comes from the randomised controlled trial conducted by Clarke et al. (2008), which compared HBOT with sham treatment. Significant improvements were observed in SOMA-LENT scores among patients receiving HBOT, with an estimated number needed to treat of approximately three patients.
However, findings have not been entirely consistent.
The HOT2 trial (2016) did not demonstrate a statistically significant benefit of HBOT when added to contemporary standard care. Consequently, the role of HBOT in radiation proctitis remains an area of ongoing debate. Nevertheless, some specialist centres continue to offer HBOT for carefully selected patients with persistent symptoms despite conventional treatment.
Other Radiation-Induced Injuries
Because many radiation injuries share common mechanisms—including chronic hypoxia, impaired vascularity and fibrosis—HBOT has been proposed as a treatment option for other radiation-induced conditions.
Current evidence for these indications is generally limited to case reports, small case series and observational studies.
Reported indications include:
- Head and neck soft tissue radionecrosis
- Radiation-induced brachial plexopathy
- Radiation-induced transverse myelitis
- Radiation-induced optic neuropathy
At present, evidence is insufficient to support firm conclusions regarding efficacy for these conditions, and treatment decisions are typically made on an individual basis within specialist multidisciplinary teams.
For further information regarding these indications, please contact info@ddrc.org.
Additional Recommended References
Alongside the references already listed, I would recommend adding the following contemporary guidance documents and reviews:
UHMS Hyperbaric Oxygen Therapy Indications Manual
Hampson NB (Ed). Hyperbaric Oxygen Therapy: Indications. Undersea and Hyperbaric Medical Society. Latest Edition.
European Committee for Hyperbaric Medicine (ECHM)
Mathieu D, Marroni A, Kot J. Tenth European Consensus Conference on Hyperbaric Medicine. Diving Hyperb Med. 2017;47(1):24–32.
Contemporary ORN Review
Forner LE, Dieleman FJ, Shaw RJ, et al. Hyperbaric oxygen treatment of mandibular osteoradionecrosis. Radiother Oncol. 2022;166:137–144.
These additions demonstrate awareness of current international guidance and the evolving evidence base surrounding osteoradionecrosis.