Radiotherapy remains a mainstay treatment of a variety of cancers throughout the body. The dose given and the area it is directed at, have all improved hugely over the past two decades. Unfortunately, it is often inevitable that some normal body tissue near the cancer, can also receive radiotherapy. Most people are aware of the possible immediate side-effects of radiotherapy such as tiredness and skin changes but the longer-term effects, which can occur months or years after radiotherapy are less well known. Over time, oxygen levels in tissue may drop, small blood vessels may reduce in density and the number of cells, the building blocks of the body, may reduce in number. The area of tissue may even die, known as radionecrosis.
Depending on where in the body is affected, this can cause different problems. In general terms, the structure and function of that part of the body will be adversely affected, such that the tissue is not able to work normally or to heal if damaged. Bone, skin or body organs such as the bowel or bladder can be affected.
Hyperbaric oxygen (HBO) is used either to:
- prevent tissue death, for instance if surgery is planned in an area that has been previously exposed to radiotherapy
- help in treatment of already damaged tissue, for instance bowel damage after radiotherapy for prostate cancer
HBO cannot resurrect dead tissue but can help stimulate small blood vessel growth into tissue damaged by radiotherapy, so improving function of the tissue and improving healing.
HBO and Head & Neck Cancers
Prevention of Osteoradionecrosis (ORN) – bone death caused by radiotherapy
The lower jaw, the mandible, might receive radiotherapy during treatment for cancers such as cancer of the tongue, tonsil, palate or mouth. After radiotherapy, saliva production is often reduced. This has an adverse impact on dental health. Dentists usually refer people needing a tooth removed in an area which has previously received radiotherapy to a Maxillofacial surgeon. This is because dental procedures may precipitate deterioration in the bone to the point that part of the bone may not heal and even die. If this occurs more extensive surgery may be required to remove the dead bone.
When bone death has occurred, the bone usually needs to be removed. ORN can even cause bone to spontaneously fracture as it loses its strength. This can involve major surgery if reconstruction is needed.
HBO can help areas of bone not yet dead but affected by the radiotherapy. This not only can help prevent further bone death but can help make it more obvious during surgery which tissue is likely to survive and which needs removal.
Hyperbaric oxygen (HBO) before and after dental work has been recognised to help prevent this bone death in people who have had radiotherapy.
A common course of treatment in this instance would be 20/30 once daily HBO, 5 days per week before dental work, 10 HBO sessions afterwards.
HBO & Pelvic Cancers
When a person undergoes radiotherapy for a problem such as prostate or cervical cancer, as the other organs in the pelvis are in close proximity – they too can be affected.
Over months and years radiotherapy can affect how well the organ functions and cause problems. Examples include radiation proctitis (inflammation of the rectum) or radiation cystitis (inflammation of the bladder).
Radiation proctitis (inflammation of the rectum due to radiotherapy)
- This can cause diarrhoea, pain, bleeding, mucous discharge and incontinence
Radiation cystitis (inflammation of the bladder due to radiotherapy)
- This can also cause pain, incontinence and bleeding
HBO can help improve what are often troublesome and uncomfortable symptoms. Symptoms such as bleeding may be severe enough to need blood transfusions. In some cases, the only other treatment option may be major surgery such as bladder removal.
A common course of treatment would be 40 sessions of HBO, once per day, 5 days per week.
Delayed radiation tissue injury is the commonest indication treated with HBO internationally and can be precipitated by an additional insult such as surgery or some kind of trauma.
The underlying pathology is a degree of obliterative endarteritis and fibrosis that causes hypocellular regions of tissue. As a result, these tissues become hypoxic and thus necrotic. The capillary density is often at 20-40% of the normal.
HBO helps by:
- Stimulating angiogenesis secondarily improving tissue oxygenation (Marx, 1990)
- Reducing fibrosis (Feldmeier, 1998)
- Mobilising and inducing an increase of stem cells within irradiated tissues (Thom, 2005)
Mandibular Osteoradionecrosis
HBO can be used in the treatment of ORN and as prophylaxis when dental procedures are planned.
Approximately 85% of individuals with osteoradionecrosis have been reported to resolve with conservative measures. However, chronic, progressive or those complicated by soft tissue necrosis will often benefit from HBO. It is used as an adjunct to standard operative intervention following the Marx protocol.
Individuals are graded and treated as follows:
Stage 1
- Underlying pathology: Exposed bone with no serious manifestations as per stage III
- Surgery: Minor bony debridement
- HBO: 30 pre-operative and 10 post operative sessions
Stage 2
- Underlying pathology: Stage I patients showing limited progress OR more extensive surgery planned
- Surgery: Minor bony debridement
- HBO: 30 pre-operative and 10 post operative sessions
Stage 3
- Underlying pathology: Stage I or II patient showing limited progress OR pathological fracture, orocutaneous fistulae, evidence of lytic involvement extending to the inferior mandibular border
- Surgery: Major bony debridement and/or reconstructive surgery
- HBO: 30 pre-operative and 10 post operative sessions PLUS additional 10 after further surgery
Research
There were two recent studies on the impact of HBO that are of note.
More recent trials have been less in favour of Hyperbaric oxygen, but most importantly highlight the rarity of radiation tissue damage with modern radiotherapy techniques.
The HOPON trial data was released in 2019. This looked at the value of HBO in prevention of ORN in those who had dental extraction in previously irradiated tissue. This was halted owing to low incidence in ORN in all numbers. The paper can be found in our research files here.
The DAHANCA-21 study followed this and was published in 2021. The study showed that those who had adjunctive Hyperbaric oxygen alongside their operative interventions had better outcomes. However, the numbers were small, and it was not statistically significant. Also, of note the patients who received HBO had improvement in subjective symptoms that often have a big impact on quality of life, i.e. xerostomia, dysphasia and salivary flow. An area of possible future development. This paper can be found here.
Radiation Cystitis and Proctitis
The use of radiotherapy in the treatment of various pelvic tumours can result in damage to the soft tissues of neighbouring organs. In both radiation cystitis and proctitis the same pathological process occurs resulting in bleeding and frequency of micturition or defaecation. In severe cases this can result in hospital admission with transfusions being required.
Cystitis
The UHMS have reviewed the data from multiple case series and the review by Feldmeier and Hampson (2002). They found 18 out of 19 published series applying HBO to radiation cystitis are positive reports. More specifically of the total 257 patients 196 (76.3%) had either partial or complete response.
Proctitis
Again, the UHMS have reviewed the data from multiple case series and found out of 199 cases of proctitis, colitis and enteritis treated with HBO, 41% had complete resolution while 86% experienced at least a partial response. Only 14% failed to respond at all.
A RCT has been done by Clarke at al(2008) where individuals were given either HBO or sham treatments at 1.1ATA. Their response was measured with SOMA-LENT questionnaires for up to an average of 1 year. A statistically increased improvement in scores was seen with a p-value of 0.0019. The absolute risk reduction was 32% and NNT 3.
More recently the HOT 2 trial completed in 2016 and this suggested that there was no statistically significant benefit to HBO alongside gold standard treatment. However, clinically improvements are often still seen and referrals still accepted. The paper can be read here.
Other Radiation Tissue Injuries
Given the pathological process and the actions of HBO it is reasonable to assume that HBO will have a similar effect on other soft tissues damaged by radiotherapy.
Case reports have been reported benefits with the following:
- Soft tissues of head and neck
- Chest wall necrosis following breast cancer
- Transverse myelitis
- Optic neuritis
- Radiation Induced Brachial Plexopathy
For information and references regarding these indications please contact us on info@ddrc.org.
Further information regarding the Referral and Funding process can be found here.
References
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