Soft Tissue Radiation Injuries

Written By Elizabeth Gaffney

Hyperbaric Oxygen Therapy in the Treatment of Soft Tissue Radiation Injuries

Introduction

Hyperbaric oxygen therapy (HBOT), which involves breathing pure oxygen in a pressurised chamber, has a number of benefits as an adjunctive treatment of soft tissue radiation injuries (STRI), such as radionecrosis. STRI are associated with vascular injury and inflammation, which lead to reduced blood flow and hypoxia, chronic wounds, tissue necrosis, and fibrosis. HBOT enhances oxygen delivery to the affected tissues, promotes angiogenesis, reduces inflammation and supports tissue repair, and there is robust clinical evidence supporting its use as an adjunctive treatment for STRI.

Mechanisms of Action of HBOT

HBOT aids in the treatment of STRI through several physiological mechanisms, primarily by enhancing tissue oxygenation and promoting healing processes. During HBOT, patients are treated with pure oxygen in a chamber in which the pressure is higher than atmospheric pressure (2 ATA) for 1.5 hours for multiple sessions.

1. Enhanced oxygenation: Radiation-induced damage to blood vessels often leads to chronic hypoxia in the affected tissues but, by increasing the amount of oxygen dissolved in blood plasma, HBOT significantly enhances 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 the 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: STRI are associated with chronic inflammation and HBOT modulates the inflammatory response by reducing pro-inflammatory and increasing anti-inflammatory cytokine activity (Cannellotto et al., 2024).

5. Antimicrobial effects: By increasing oxygen levels in tissues, HBOT inhibits the growth of anaerobic bacteria and enhances the activity of leukocytes (Memar et al., 2019; Cannellotto et al., 2024), thereby aiding in the resolution of infections that often complicate STRI.

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

Benefits of HBOT for Patients with STRI

HBOT is generally well tolerated and serious side effects are rare (Camporesi, 2014). Patients with STRI can experience numerous benefits from adjunctive 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 STRI, shortening the duration of symptoms, reducing the need for additional treatments, and improving overall recovery times.

2. Pain relief: STRI are often associated with chronic pain, and 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 STRI, reducing long-term disability and improving patients’ quality of life.

4. Prevention of infections: STRI 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 STRI

Numerous studies and clinical trials support the use of HBOT in the treatment of STRI. 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 STRI.

1. Systematic reviews and meta-analyses: A Cochrane review concluded that HBOT of STRI (typically 100% O2, 2–2.5 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 STRI (Feldmeier et al., 2002).

2 Soft tissue radionecrosis: Radiation-induced necrosis can occur in various soft tissues, including the skin and subcutaneous tissue, leading to chronic non-healing wounds and ulceration. By promoting wound healing, reducing inflammation, and preventing infection, HBOT (100% O2, 2–2.5 ATA, 60–120 mins, 30–60 sessions) may be beneficial in the treatment of STRI (Tahir et al., 2014), including radiation-induced skin necrosis (Borab et al., 2017). A review by Hoggan and Cameron (2014) concluded that HBOT (e.g. Filntisis et al., 2010; 100% O2, 2 ATA, 120 mins, 6–80 sessions) may offer clinical benefits to patients suffering from post-radiation injuries of the head and neck

3. Radiation proctitis: Radiation proctitis is characterised by inflammation, ulceration, and fibrosis of the rectum following pelvic radiotherapy. Clinical evidence indicates that HBOT (100% O2, 2–2.5 ATA, 60–120 mins, 3–80 sessions) is effective in reducing symptoms and promoting healing in patients with chronic radiation proctitis (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.

4. Ophthalmic STRI: Eighteen sessions of HBOT at 2 ATA for 90 mins has been reported to be beneficial in the treatment of radiation-induced macular ischaemia (Haji & Frenkel, 2010) and to preserve visual function in optic neuropathy (Malik & Golnik, 2012).

Conclusion

HBOT offers a promising adjunctive treatment for STRI by enhancing oxygen delivery, promoting angiogenesis, and reducing inflammation and the risk of infection. Clinical evidence, including randomised controlled trials, systematic reviews, and case reports, supports the benefits of HBOT in accelerating healing, alleviating pain, improving functional outcomes and preventing complications in patients with STRI.

References

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

  • Bhutani, S., & Vishwanath, G. (2012). Hyperbaric oxygen and wound healing. Indian Journal of Plastic Surgery, 45(02), 316-324.

  • 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.

  • 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.

  • 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.

  • Fernández, E., Morillo, V., Salvador, M., Santafé, A., Beato, I., Rodríguez, M., & Ferrer, C. (2021). Hyperbaric oxygen and radiation therapy: a review. Clinical and Translational Oncology, 23(6), 1047-1053.

  • Filntisis, G. A., Farmer, J. C., Moon, R. E., Scher, R. L., Kraft, K. L., & Piantadosi, C. A. (2000). Laryngeal radionecrosis and hyperbaric oxygen therapy: Report of 18 cases and review of the literature. Annals of Otology, Rhinology & Laryngology, 109(6), 554-562.

  • 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.

  • Haji, S. A., & Frenkel, R. E. (2010). Hyperbaric oxygen therapy for the treatment of radiation-induced macular ischemia. Clinical Ophthalmology, 433-436.

  • Hoggan, B. L., & Cameron, A. L. (2014). Systematic review of hyperbaric oxygen therapy for the treatment of non-neurological soft tissue radiation-related injuries. Supportive Care in Cancer, 22, 1715-1726.

  • 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.

  • Malik, A., & Golnik, K. (2012). Hyperbaric oxygen therapy in the treatment of radiation optic neuropathy. Journal of Neuro-Ophthalmology, 32(2), 128-131.

  • 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.

  • 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.

  • 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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