In the UK, it is estimated that over 3 million individuals currently live with cancer. Radiotherapy is an essential part of cancer treatment, leading to 40% of global cancer remissions as well as improving the quality of life for many others patient affected by cancer. Unfortunately, radiation does not just destroy or inhibit the proliferation of cancer cells, but it can also impact neighbouring normal cells.
Healthy cells damaged during radiation therapy usually recover within a few months post-treatment. However, some individuals may experience persistent side effects, while others may develop late-onset complications in the months or even years following the conclusion of radiation treatment. These complications may not resolve on their own and can significantly impact patients’ well-being, requiring continuous medical care. One of the major adverse effects associated with radiation therapy is the occurrence of radiation necrosis, a rare but devastating side effect. It is included in HBOT indication list of two important scientific committees, Undersea and Hyperbaric Medical Society (UHMS) and European Committee for Hyperbaric Medicine (ECHM).
Rationale for Clinical Application
Hyperbaric oxygen therapy is being utilised for treatment of radionecrosis since 1975 with numerous publications. However, the accessibility of hyperbaric oxygen therapy (HBOT) is restricted due to limited availability of medical hyperbaric oxygen facilities, cost, and duration of treatment needed.
HBOT is a non-invasive therapy that can be used alongside radiation therapy and chemotherapy as well as for treating RNs. An appropriate number of daily treatments are necessary for angiogenesis to occur. As a treatment of RN, the typical protocol entails 30 to 60 sessions taken daily; each session lasts about 90 to 120 minutes. But the protocols should be individualised based on the extent of necrosis and tissue involvement.
The mechanisms and rationale for employing HBOT in the treatment of radiation injuries are as follows:
- Enhanced Oxygenation and Reduction of Hypoxia-Induced Effects: HBOT helps to mitigate the effects of hypoxia (low level of oxygen in tissues) by directly supplying oxygen to ischemic tissues. Radiation-induced hypoxia contributes to cell death and tissue necrosis. By alleviating hypoxia, HBOT helps to prevent the progressive cell death that leads to necrosis. (Bennett et al., 2004)
- Angiogenesis: HBOT stimulates the growth of new blood vessels in damaged tissues mainly through increased production of vascular endothelial growth factor (Godman et al., 2010). This is critical because radiation damage often impairs vasculature, which is necessary for delivering oxygen and nutrients to tissue for healing. Tissue oxygen studies have shown that angiogenesis becomes measurable after eight treatments. At 20 sessions, it reaches a plateau at 80-85% of non-irradiated tissue vascularity. The changes induced by HBO therapy on the tissue’s oxygen pressure appear to be largely permanent, as, 3 years after completion of HBO treatment, oxygen pressure in the tissue has been observed to be 90% of what it was at the end of the treatment. (Mayer et al., 2005). This facilitates the healing of tissues damaged by radiation by improving blood flow and providing an oxygen-rich environment for cell regeneration.
- Reduced Oedema: Radiation-induced tissue damage often leads to oedema, worsening hypoxia by compressing nearby blood vessels. Hyperbaric Oxygen Therapy helps reduce oedema through vasoconstriction, improved oxygenation, and reduced inflammation. These mechanisms can decrease swelling and improve tissue function.
- Anti-inflammatory effects: Hyperbaric Oxygen Therapy has anti-inflammatory effects through multiple mechanisms. It reduces production of pro-inflammatory cytokines, inhibits leukocyte adhesion to blood vessel linings, decreases oedema, utilizes oxygen as a signalling molecule for modulating the inflammatory response, and enhances production of anti-inflammatory mediators. (Feldmeier et al., 2002)
- Pain Management: Hyperbaric Oxygen Therapy may help cancer patients manage pain, especially those undergoing radiation therapy. It can improve tissue healing after radiation-induced damage, reduce inflammation, promote new blood vessel formation for better oxygenation and blood flow to damaged tissues, and effectively manage neuropathic pain. (Meier et al., 2022). While existing research is promising, the effectiveness of HBOT for pain management in cancer patients can vary and should be evaluated by healthcare providers on a case-by-case basis.
- Wound healing: Several studies have indicated that HBOT supports healing in radiation necrosis by increasing rates of wound closure and reducing the size of wounds, as well as alleviating pain and inflammation symptoms. The oxygen-rich environment created by HBOT can stimulate the proliferation of fibroblasts, increasing the number of these cells available to repair and rebuild damaged tissue. It also aids re-epithelialization and encourages collagen production, potentially lowering the occurrence of wound separation in radiated tissue. (Lin et al.,2023) (Feldmeier et al., 2002)
- Fibroblast Activation: The oxygen-rich environment created by HBOT can stimulate the proliferation of fibroblasts, increasing the number of these cells available to repair and rebuild damaged tissue. (Kang et al., 2004)
- Inhibition of Osteoclasts: Particularly in the case of osteoradionecrosis, HBOT may inhibit the activity of osteoclasts (cells that break down bone) while stimulating osteoblasts (cells that form bone), leading to bone regeneration and healing. (Al Hadi et al.,2014)
Summary
Radiotherapy, when indicated, is crucial in the treatment of cancer. It has been shown to achieve a 40% worldwide remission rate and improve the quality of life for many patients. However, it can also impact neighbouring normal cells, leading to persistent side effects or late-onset complications. Radiation necrosis leads to development of wound beds that are hypoxic-hypocellular, and hypovascular. Hyperbaric oxygen therapy is often the only form of treatment that provides relief for these individuals.
In USA, patients with radiation tissue injuries are widely treated with HBOT, and insurance companies reimburse this therapy when the eligibility criteria are met. However, most UK insurance companies still do not cover the cost of this treatment, which is disappointing for patients. There is no justification for denying the treatment, as it has been scientifically validated as a safe and effective option with no other alternative available. In addition, it is approved by regulatory bodies such as FDA, UHMS, and EUBS.
The typical protocol entails 30 to 60 sessions taken daily; each session lasts about 90 to 120 minutes. But, it should be customised and integrated with conventional oncology and surgical treatments, with specific plans tailored to suit each individual case, based on the extent of necrosis and tissue involvement.
HBOT is generally safe and well-tolerated when administered correctly, but there are rare side effects, and it may not be suitable for every oncology patient. Therefore, patients need careful assessment by a physician with expertise in hyperbaric oxygen medicine before considering this therapy as an adjunctive treatment option.