Radiation Injury

Written By Elizabeth Gaffney

Hyperbaric Oxygen Therapy in the Treatment of Post-Radiation Injuries

Introduction

Hyperbaric Oxygen Therapy (HBOT) consists of breathing oxygen at a pressure higher than local atmospheric pressure for multiple sessions for the treatment or prevention of specific diseases. As per the European Code of Good Practice (Kot et al.), there is a general consensus that the term HBOT can only be applied when the partial pressure of oxygen in breathing mixture exceeds 1.5 absolute atmosphere (ATA) for a minimum period of 60 minutes (excluding compression and decompression).

HBOT may benefit patients with post-radiation injuries such as radiation cystitis, radiation proctitis, osteoradionecrosis and soft-tissue necrosis. Radiation injuries are associated with hypoxia, vascular injury, inflammation and fibrosis. HBOT can enhance oxygen delivery, promote angiogenesis, reduce inflammation, and support tissue repair, and there is robust clinical evidence supporting its use as an adjunctive treatment for radiotherapy-induced injuries.

Mechanisms of Action of HBOT

HBOT aids in the treatment of post-radiation injuries through several physiological mechanisms, primarily by enhancing oxygen delivery to damaged tissues, particular bone tissues in the case of osteoradionecrosis and promoting healing processes.

1. Enhanced oxygenation: Radiation-induced damage to blood vessels often leads to chronic hypoxia in the affected tissues. HBOT increases the amount of oxygen dissolved in blood plasma, significantly enhancing oxygen delivery to hypoxic tissues (Cannellotto et al., 2024).

2. Angiogenesis: HBOT stimulates angiogenesis by increasing the production of VEGF and other growth factors, restoring blood supply to irradiated tissues (Marx et al., 1990).

3. Collagen synthesis: HBOT promotes fibroblast proliferation and collagen synthesis, both of which are essential for tissue repair (Bhutani & Verma, 2010).

4. Anti-inflammatory effects: Radiation-induced tissue damage is often accompanied by chronic inflammation, which may be alleviated by HBOT via a reduction in pro-inflammatory cytokines and increased anti-inflammatory cytokine activity (Cannellotto et al., 2024).

5. Antimicrobial effects: HBOT inhibits the growth of anaerobic bacteria and enhances the activity of leukocytes, thereby aiding in the resolution of infections that often complicate post-radiation injuries (Memar et al., 2019; Cannellotto et al., 2024).

6. Promotion of stem cell activity: HBOT mobilises stem cells from the bone marrow, aiding in tissue repair and regeneration (Thom et al., 2006).

Benefits of HBOT for Patients with Post-Radiation Injuries

HBOT is generally well tolerated and serious side effects are rare (Camporesi, 2014). Patients with post-radiation injuries can experience numerous benefits from HBOT, leading to improved outcomes and quality of life (Fernández et al., 2020).

1. Accelerated healing: One of the most significant benefits of HBOT is the acceleration of the healing process (Bhutani & Vishwanath, 2012). Enhanced oxygenation, angiogenesis, and fibroblast activity contribute to faster resolution of radiation-induced injuries, shortening the duration of symptoms, reducing the need for additional treatments, and improving overall recovery times.

2. Pain relief: Post-radiation injuries are often associated with chronic pain, which can be severe and difficult to manage. HBOT can help alleviate pain by reducing inflammation and promoting tissue repair.

3. Improved functional outcomes: By accelerating healing and reducing the risk of complications, HBOT can improve functional outcomes for patients with post-radiation injuries, reducing long-term disability and improving patients’ quality of life.

4. Prevention of infections: Post-radiation injuries are prone to infections, and HBOT’s antimicrobial effects and its role in promoting wound healing help prevent infections and reduce the risk of long-term adverse outcomes.

Clinical Evidence Supporting HBOT of Post-Radiation Injuries

Numerous studies and clinical trials support the use of HBOT as an adjunctive treatment for post-radiation injuries. HBOT at 2 ATA or above is recognised by the US FDA for the treatment of radiation injuries. The Undersea and Hyperbaric Medical Society (UHMS) has published guidelines for HBOT (≥2 ATA) for radiation-induced injuries and supports the integration of HBOT into clinical practice for managing post-radiation injuries.

1. Systematic reviews and meta-analyses: A Cochrane review concluded that HBOT for late radiation tissue injury (typically 100% O2, ³2 ATA, 60–120 mins, 30–60 sessions) is associated with improved outcomes for patients with radiation injuries of the head, neck, anus and rectum, including a reduced risk of wound dehiscence and a reduction in pain (Lin et al., 2023). A systematic review recommended HBOT at ≥2 ATA for the treatment of soft tissue and bony radiotherapy-induced injuries (Feldmeier et al., 2002).

2. Radiation proctitis: HBOT at 2.4 ATA for 90 mins (40 sessions) promoted mucosal healing, reduced bleeding and promoted rectal function in patients with proctitis caused by radiation therapy for pelvic cancers (Glover et al., 2016; Clarke et al., 2008; Tahir et al., 2014). A meta-analysis by Yuan et al. (2020) concluded that HBOT may alleviate radiotherapy-related gastrointestinal complications, including rectal bleeding, diarrhoea and pain.

3. Radiation cystitis: Radiation cystitis, a complication of pelvic radiation therapy, results in inflammation and fibrosis of the bladder, leading to haematuria, pain, and urinary dysfunction. HBOT at 2–3 ATA for 90 mins (≥20 sessions) significantly reduced haematuria and improved bladder function in patients with radiation cystitis (Bevers et al., 1995; Oliai et al., 2012; Tahir et al., 2014; Cardinal et al., 2018).

4. Osteoradionecrosis: Radiation therapy may lead to osteonecrosis, particularly in the mandible following head and neck cancer treatment. Some studies (e.g. Dieleman et al., 2017) suggest that HBOT (100% O2, 2.4 ATA, 90 mins, 20 sessions before surgery and 10 after) may benefit patients with osteoradionecrosis by promoting bone healing, reducing infection risk and enhancing surgical outcomes (Tahir et al., 2014; Korambayil et al., 2020; Freiberger & Feldmeier, 2010).

5. Mandibular osteoradionecrosis: Hyperbaric oxygen also has a frequent application in the prevention of mandibular osteoradionecrosis when dental extractions are required from heavily irradiated mandibles (Marx, 2019).

Conclusion

HBOT is a promising adjunctive treatment for post-radiation injuries by enhancing oxygen delivery, promoting angiogenesis, reducing inflammation, and improving immune function. Clinical evidence supports the use of HBOT in accelerating healing, alleviating pain, improving functional outcomes, and preventing complications.

References

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  • Bhutani, S., & Verma, R. (2010). Hyperbaric oxygen therapy in non-healing wounds. Journal of Marine Medical Society, 12(2), 89-92.

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  • Borab, Z., Mirmanesh, M. D., Gantz, M., Cusano, A., & Pu, L. L. (2017). Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Journal of Plastic, Reconstructive & Aesthetic Surgery, 70(4), 529-538.

  • Camporesi, E. M. (2014). Side effects of hyperbaric oxygen therapy. Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc, 41(3), 253-257.

  • Cannellotto, M., Yasells García, A., & Landa, M. S. (2024). Hyperoxia: Effective Mechanism of hyperbaric treatment at mild-pressure. International Journal of Molecular Sciences, 25(2), 777.

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  • Clarke, R. E., Tenorio, L. C., Hussey, J. R., Toklu, A. S., Cone, D. L., Hinojosa, J. G., … & Walker, M. B. (2008). Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. International Journal of Radiation Oncology* Biology* Physics, 72(1), 134-143.

  • Dieleman, F. J., Phan, T. T. T., Van den Hoogen, F. J. A., Kaanders, J. H., & Merkx, M. A. (2017). The efficacy of hyperbaric oxygen therapy related to the clinical stage of osteoradionecrosis of the mandible. International Journal of Oral and Maxillofacial Surgery, 46(4), 428-433.

  • Feldmeier, J. J., & Hampson, N. B. (2002). A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: An evidence based approach. Undersea & Hyperbaric Medicine, 29, 1.

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  • Freiberger, J. J., & Feldmeier, J. J. (2010). Evidence supporting the use of hyperbaric oxygen in the treatment of osteoradionecrosis of the jaw. Journal of Oral and Maxillofacial Surgery, 68(8), 1903-1906.

  • Glover, M., Smerdon, G. R., Andreyev, H. J., Benton, B. E., Bothma, P., Firth, O., … & Yarnold, J. (2016). Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial. The Lancet Oncology, 17(2), 224-233.

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  • Korambayil, P. M., Ambookan, P. V., Pillai, S., Karangath, R. R., & George, D. (2020). Role of hyperbaric medicine for osteoradionecrosis and post irradiation wounds: an institutional experience. Indian Journal of Surgical Oncology, 11, 469-474.

  • Lin, Z. C., Bennett, M. H., Hawkins, G. C., Azzopardi, C. P., Feldmeier, J., Smee, R., & Milross, C. (2023). Hyperbaric oxygen therapy for late radiation tissue injury. The Cochrane Database of Systematic Reviews, 8(8), CD005005.

  • Marx, R. E., Ehler, W. J., Tayapongsak, P., & Pierce, L. W. (1990). Relationship of oxygen dose to angiogenesis induction in irradiated tissue. The American Journal of Surgery, 160(5), 519-524.

  • Marx RE, Feldmeier JJ, Johnson RP. Hyperbaric oxygen is still needed in the management and prevention of mandibular necrosis: a response to Mr. Richard Clarke. Undersea Hyperb Med. 2019 Jun-Jul-Aug – Third Quarter;46(4):399-408.

  • Memar, M. Y., Yekani, M., Alizadeh, N., & Baghi, H. B. (2019). Hyperbaric oxygen therapy: Antimicrobial mechanisms and clinical application for infections. Biomedicine & Pharmacotherapy, 109, 440-447.

  • Oliai, C., Fisher, B., Jani, A., Wong, M., Poli, J., Brady, L. W., & Komarnicky, L. T. (2012). Hyperbaric oxygen therapy for radiation-induced cystitis and proctitis. International Journal of Radiation Oncology* Biology* Physics, 84(3), 733-740.

  • Tahir, A. R. M., Westhuyzen, J., Dass, J., Collins, M. K., Webb, R., Hewitt, S., … & McKay, M. (2015). Hyperbaric oxygen therapy for chronic radiation‐induced tissue injuries: Australasia’s largest study. Asia‐Pacific Journal of Clinical Oncology, 11(1), 68-77.

  • Thom, S. R., Bhopale, V. M., Velazquez, O. C., Goldstein, L. J., Thom, L. H., & Buerk, D. G. (2006). Stem cell mobilization by hyperbaric oxygen. American Journal of Physiology-Heart and Circulatory Physiology, 290(4), H1378-1386.

  • Yuan, J. H., Song, L. M., Liu, Y., Li, M. W., Lin, Q., Wang, R., … & Dong, J. (2020). The effects of hyperbaric oxygen therapy on pelvic radiation induced gastrointestinal complications (rectal bleeding, diarrhea, and pain): a meta-analysis. Frontiers in Oncology, 10, 390.

Elizabeth Gaffney https://www.sourceprojects.co
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