Hyperbaric Oxygen Therapy Indications Simplified

Indication #3: Radiation Injuries

Radiation-induced tissue injuries are a result of direct toxicity secondary to exposure to radiation. These injuries are most seen in the setting of malignancy, where radiation is being delivered for therapeutic purposes. The delivery of the radiation in these instances is very purposeful, and the physician delivering the radiation takes into consideration the location, target, and appropriate dosage.

The mechanism of action of radiation therapy is twofold. It can damage DNA by affecting its structure and inducing DNA breaks, which is direct cellular damage. It can also induce reactive oxygen species (ROS) generation, which can then oxidize lipids and proteins as well as induce further damage to DNA. This would be considered indirect cellular damage.¹

It is important to note that tissues vary in their tolerance to radiation.² Some tissues and cells are more radiosensitive. For example, immature, undifferentiated, and actively dividing cells are much more radiosensitive than their counterparts, making radiotherapy an efficacious cancer treatment.³

Overall, after being exposed to radiation, malignant cells suffer death. Sometimes this comes at the cost of normal tissue cell death, which can lead to damage to blood vessels (obliterative endarteritis)^4,5 as well as the replacement of normal tissue cells with more dense connective tissue, a process known as fibrosis. Radiation-induced apoptosis and exuberant fibrosis are the predominant causes of delayed radiation injuries.^4,5 It has also been demonstrated that chronically hypoxic tissues are subject to exuberant fibrosis mediated by hypoxia-inducible factor (HIF)-1.⁶ These processes can then lead to further tissue breakdown, which can precipitate the onset of ulcers, wounds, and even necrosis.⁷

Incidence of Radiation Therapy and Associated Complications

The likelihood of experiencing a radiation-induced tissue injury tightly correlates to the dosage of radiation delivered. Bryant et al discussed the trends in radiation therapy among cancer survivors in the US and reported that most of the radiation-treated cancer survivors were those who were treated for breast cancer.⁸ Their projections revealed that in 2016, 1.25 million cancer survivors were treated with radiation therapy, which accounted for 29% of all cancer survivors in the US. They estimated that this number would increase to 2.01 million by 2030, highlighting the importance of radiation therapy in the treatment and survival of our cancer patients and shining a light on the need for research and increased knowledge of radiation and its sequalae.⁸

Some sources estimate that by the end of 2022 there will have been about 1.2 million cancer cases diagnosed in the US, of which half will require radiation therapy. Of those who receive therapy in 2022, it is estimated that 5%, or 30,000 cases, will develop serious radiation complications.⁹

Types of Radiation-Induced Injuries and Serious Complications of Radiation Therapy

Radiation injuries can be further classified into acute (immediate), subacute (8–12 weeks), and delayed (after 6 months). This classification refers to the onset of the symptoms related to the radiation injury. Often, the onset is closely related to the dose of radiation administered as well as the type of tissue involved. Radiation is dosed in both rads and grays. One centigray (cGy) is equal to 1 rad.⁹ In the case of acute and subacute injuries, these both have been linked to radiation therapies exceeding 5000 cGy.

Acute injuries are likely to develop symptoms immediately or shortly after exposure to radiation, while subacute injuries can show symptoms two to three months after exposure.¹⁰

Delayed or late radiation injuries tend to appear within months to even years after radiation exposure.¹¹ These injuries are typically seen in tissue that has a slower cell turnover rate such as the kidney, liver, brain, fatty tissue, intestines, and subcutaneous tissue.¹² Symptoms of radiation injuries are highly dependent on the location and extent of the injury. For example, radiation administered to the chest for breast cancer can lead to dermatitis of the tissue overlying the area, but can also lead to more serious complications such as pericardial disease, arrhythmias, and cardiomyopathy.¹³ Head and neck radiation can cause symptoms that range from xerostomia to dysphagia, and even osteoradionecrosis of the jaw.

Additionally, one of the most commonly seen radiation-induced tissue injuries in hyperbaric medicine is radiation-induced cystitis, which can be treated very effectively with hyperbaric oxygenation therapy (HBOT). Lastly, radiation has the potential to induce secondary malignancy. The absolute risk for this ranges between 0.2% and 1% per year in cancer survivors after radiotherapy, with the first peak in the bimodal distribution being within the first three years after treatment and relating to hematologic malignancies. The second peak is commonly seen after a decade of radiation therapy and is closely related to solid malignancies.¹⁴

HBOT Treatment for Radiation-Induced Tissue Injuries

HBOT has been used as a treatment for delayed radiation damage since the 1970s.^15,16 Currently, radiation injuries are an approved indication for HBOT by both the Undersea and Hyperbaric Medicine Society (UHMS) and the Food and Drug Administration (FDA). Much of the effects of HBOT on irradiated tissue come from its well-known angiogenic effects, as we know that during radiation-induced tissue injuries, there is the obliteration of the vessels leading to hypoxia. Overall, there seems to be a consensus regarding the mechanism of HBOT as a treatment for radiation injuries, with angiogenesis being the leading mechanism, followed by the reduction of tissue fibrosis and the increase in mobilization and stimulation of an increased number of stem cells in the damaged tissues.¹⁷

HBOT could also be used in the prophylaxis of radiation injuries, particularly in the small bowel, which Feldmeier et al demonstrated in a murine model, information which we continue to use as a foundation for research.¹⁸ Geldof et al recently investigated the result of HBOT in women with gynecological malignancies who developed late radiation-induced tissue toxicity, showing that HBOT indeed has a positive effect on the symptom severity in these patients.¹⁹

HBO₂ Treatment for Mandibular ORN

Marx 30/10 protocol. Treat 90 O₂ minutes at 2.4 ATA as adjunct therapy with appropriate surgical management

Neoadjucant HBO₂ Prior to Dental Extractions

Marx 20/10 Protocol—20 treatment pre-extraction, 10 post extraction, each 90 O₂ minutes at 2.4 ATA

HBO₂ for Soft Tissue Radiation Necrosis

HBO₂ at 2.4 ATA for 90 minutes oxygen minutes plus advanced wound care—30–60 treatments may be required.

HBO₂ for Radiation Cystitis or Proctitis

HBO₂ at 2.4 ATA for 90 minutes oxygen minutes for 40–60 treatments

HBO₂ for CNS Radiation Necrosis

HBO₂ at 2.4 ATA for 90 oxygen minutes for 40–60 treatments

Word to the Wise

·      While radiation therapy is very efficacious in the setting of cancer treatment, it is not without consequence and radiation injuries can happen.
·      Clinicians must take a thorough history and exam to promptly identify radiation injuries, whether they be acute, subacute, or delayed so that patients can be referred to the appropriate specialist and be provided with treatment in a timely fashion
·      A role for HBOT in acute or subacute radiation injuries has not been well studied or established but there is some interest in evaluation role of HBO.²⁰
·      Evidence based data exists for adjuvant use of HBO therapy in delayed radiation injuries.⁵
·      Patient should be referred back to oncology team for management of malignancy if malignancy is still present in wound.⁵
·      Research and review so far do not show that hyperbaric oxygen therapy promote malignant growth.⁵
 
Denise Nemeth is a second-year medical student at the University of the Incarnate Word School of Osteopathic Medicine in San Antonio, TX. Formerly a general and vascular surgery PA in a rural community, Ms. Nemeth aspires to become a general surgeon. She is certified wound specialist with the American Board of Wound Management. Her interests include rural health, wound healing, colorectal surgery, and minimally invasive surgery.  

Jayesh B. Shah is Immediate Past President of the American College of Hyperbaric Medicine and serves as medical director for two wound centers based in San Antonio, TX. In addition, he is president of South Texas Wound Associates, San Antonio. He is also the past president of both the American Association of Physicians of Indian Origin and the Bexar County Medical Society and Current of Board of Trustees of Texas Medical Association.  

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