Radiotherapy and Hyperbaric Oxygen Therapy (HBOT)

Cancer is a major health problem causing many premature deaths and morbidity. Importantly, it is a problem concerning not only the frail elderly. World Health Organization estimates that the expected increase in the proportion of elderly people alone will increase the incidence of cancer by approximately 50% over the next 20 years. By 2020, the annual rate will be 16 million new cases and 10.3 million deaths due to cancer globally. Primary prevention is the cornerstone of an effort to reduce this substantial burden – mainly targeting tobacco, alcohol, diet and infections. When a tumor is diagnosed, either through a screening test or after symptoms appear, treatment is given and nowadays, many forms of the disease are considered curable and there are cases where treatment results in the patient reaching normal life expectancy. However, not only fighting the disease is important but also securing quality of life. Radiotherapy is a very important type of non-surgical treatments in the fight against cancer, used therapeutically for approximately 100 years, either as the main treatment or as adjunctive. In total, 40%-50% of all cancer patients will receive some form of radiotherapy –radical or palliative– at some stage of the management of their disease. Especially in some tumors (eg head & neck) it offers excellent results and avoidance of hard, amputating operations.

Radiotherapy is the application of ionizing radiation for the treatment of disease. Delivery of ionizing radiation is done externally on the area of interest (external beam radiotherapy), local placement of radioactive material (brachytherapy) or intravenous provision of radioactive substance (internal isotope treatment). Ionizing radiation interacts with molecules and transfers energy to them causing secondary ionizations with formation of free radicals. These reactive species then, attack other molecules like DNA, lipids and proteins. DNA is the critical target for the lethal properties of radiation against tumors. Apoptosis is the second mechanism related with radiation-induced injury. An association between apoptosis and radiosensitivity has been observed.

External beam radiotherapy is the most common method in use. An important aspect of this treatment is caution for minimizing normal tissue damage while maximizing eradication of a tumor. Since radiation is not able to be directed to tumor cells only and irradiation of a small area of normal cells within its margins is considered to offer elimination of “hidden” malignant cells and protect from metastases, it’s almost inevitable to suffer radiation injury of normal tissues in varying degrees

Acute or early effects occur during or shortly after treatment and the acute period refers usually to the first 6 months after radiotherapy. They might lead to adjustment of radiotherapy if they occur during its course but are usually transient and have a good chance of healing with proper support. In other cases, radiation injury manifests later, 6 months or more after the end of radiotherapy (Chronic or late effects). Late effects are seldom transient and often progress to more severe forms of dysfunction. Some of them may cause discomfort larger than the tumor itself which may be at the time cured. All these effects are what we call post-radiation injury (also called radionecrosis, radiation/irradiation injury). There is a great variety of symptoms and signs involving all organs and tissues. Technological advances of course, have decreased its incidence but not eliminated it

According to the time of appearance after the irradiation, post-radiation injury is classified as:

  1. Acute (early): They appear in the first 90 days (others consider first 6 months after irradiation) – includes the time of irradiation
  2. Subacute: 6 – 12 months after irradiation
  3. Chronic (Late): Beyond 12 months (sometimes divided it into chronic: 2nd to 5th year & late: after the 5th year)

Post-radiation injury may progress years after radiotherapy and this is mainly due to small blood vessels damage. In that way, seemingly normal tissues may have compromised wound healing capacity and immune response. Minor trauma may lead to serious problems and there is an increased risk of infections. It has been reported that irradiated tissues have a lifelong risk for developing post-radiation injury.

Depending on the area irradiated post-radiation injury may be diagnosed as: Radiation (haemorrhagic) Cystitis – following irradiation for prostate cancer (male) or gynecological cancer (female), Radiation Proctitis – Colitis – Enteritis – after irradiation of the abdomen, Osteoradionecrosis – usually of the mandible, after irradiation of head & neck tumors, Soft Tissue Radiation Necrosis – may manifest as chronic wounds, muscle’s fibrosis, skin alterations etc. It can be said that all tissues included in the field of irradiation may be affected (other cases may be radionecrosis of the larynx, cerebral radiation necrosis and post-radiation spinal cord injury).

Hyperbaric Oxygen Therapy is an accepted excellent treatment option for management of radiation injury. As irradiation effects on normal tissues lead to hypoxia, hypovascularity and hypocellularity rendering them susceptible to infections and leading to deficient wound healing, HBOT should be and actually is, the treatment of choice. A reminder of HBOT actions that conclude that:

  1. Increased Oxygen tension to (hypoxic) tissues
  2. Stimulation of new blood vessels formation (neovascularization), collagen production and fibroblast/osteoblast proliferation
  3. Increased resistance to infection and growth factors stimulation

When compared to other treatment options, HBOT modifies effects of radiotherapy on the histological level. This way, besides healing of manifested disease, it offers long term recovery or even permanent cure. Studies have reported 95% efficiency of HBOT to treat post-radiation hemorrhagic cystitis resistant to other treatment modalities.

  • Specific cases where Hyperbaric Oxygen Therapy has a place with excellent results are:

· Osteoradionecrosis as the main treatment or combined with surgical treatment depending on the extent.

· Mandibular Osteoradionecrosis prevention before and after tooth extraction, implants and other surgeries.

· Post-Radiation Hemorrhagic Cystitis, leads to resolution of hemorrhage (60 – 95% of cases) and major improvement to quality of life.

· Radiation Dermatitis and Skin Lesions  that don’t heal, like those following lower extremity or breast cancer irradiation, especially if reconstruction using implants is planned or has already been done and aesthetic result is threatened.

· Lymphedema, commonly of the upper extremities following surgery with lymph node removal and radiotherapy. HBOT reduces edema, improves functionality and heals ulcer if present/prevents from progressing, in the context of a comprehensive strategy.

· Post-radiation proctitis – colitis

· Post-Radiation Injury involving sensitive neural tissue (brain, spinal cord or peripheral nerves).

· Re-irradiation (to the same area) to treat recurrence, in order to alleviate existing injury and prevent subsequent effects following second radiation cycle.

· Protection of Irradiated Tissues in the case of need for surgery within the area of radiation field, regardless of obvious injury present or not.