Background: Radiotherapy is a common treatment for many malignancies. Radiation-related
complications developing months or years after radiation treatment are known as late
radiation tissue injury (LRTI) and are estimated to effect 5%-15% of all long-term survivors
who have received radiation.

Hyperbaric oxygen therapy (HBOT) is a well established treatment of LRTI. Most of the studies
evaluating effect of HBOT on LRTI are focused on survival, resolution of tissue damage and
improvement in LENT-SOMA scale. Very few studies have addressed effect of HBOT on pain in
LTRI. Krahn and colleagues were the first to report the analgesic effect of HBOT in 3 cases
of refractory pain in oncological patients with radiation soft tissue injury. Other studies
showed significant improvement in pain intensity in patients with breast cancer and pelvic
malignancies treated with HBOT for LTRI. In patients that had developed radiation- induced
brachial plexopathy, HBOT elicited an increase in warm pain thresholds and a reduction in
lymphoedema. A prospective case study of 16 patients with gynecological cancer found no
changes with respect to pain and depression outcomes. A trial in patients with radiation
induced proctopathy showed that 75% of patients with rectal pain had some improvement,
although none experienced a complete resolution of pain symptoms.

There are several mechanisms by which HBOT may elicit analgesic effects. There is a growing
body of evidence that HBOT’s analgesic effect related to nitric oxide metabolism and
endogenous opioid secretion. Furthermore, the inhibition of tumor necrosis factor alph
(TNF-α), the production of substance P, and the modulation of serotonergic pathways have all
demonstrated a modification in the pain response following HBOT. In animal studies HBOT
decreased allodynia and hyperalgesia in different models of neuropathic and inflammatory
pain. The long lasting antinociceptive effect of HBOT was found to be dose-dependent in
non-injured tissues.

In human studies, HBOT decreased pain and edema and improved function in patients suffering
from the complex regional pain syndrome, and improved pain scores and range of motion in
patients with idiopathic femoral head necrosis. Women suffering from interstitial cystitis
demonstrated a reduction in pelvic pain following weeks and months of HBOT treatment. In
patients suffering from idiopathic trigeminal neuralgia HBOT produced a rapid reduction in
symptoms and these effects were lasting for 6 months following treatment. HBOT was also found
to be an effective treatment for cluster headaches and migraines and alleviated muscle and
bone pains in patients with myofascial syndrome, fibromyalgia, and biphosphonate-related
osteonecrosis of the jaw.

Based on the evidence presented above and HBOT’s known analgesic effect in many conditions,
the investigators designed this study with the objective to evaluate if HBOT reduces pain,
improves depression and impacts on patients quality of life in patients suffering from late
radiation tissue injury.

Study Design: Prospective observational study (n=300). Patients that have had radiation
therapy for malignancy, developed late radiation injury and suffer from chronic pain.