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Long Term Side Effects of Radiotherapy Professionals

Long term Side effects of Radiotherapy

HBO is often used when treating delayed radiation tissue injury. This is usually more than 6 months after a course of radiotherapy but can vary from patient to patient. It is often 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 (Goldstein, 2006)

 

Mandibular Osteoradionecrosis

HBO is used in the treatment of ORN and as prophylaxis when dental procedures are planned.

Treatment

Approximately 85% of individuals with osteoradionecrosis have been reported to resolve with conservative measures (Parsons, 1994). 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 (Marx, 1999).

Individuals are graded and treated as follows

Stage

Underlying pathology

Surgery

HBO

I

Exposed bone with no serious manifestations as per stage III

Minor bony debridement

30 pre-operative and 10 post operative sessions

II

Stage I patients showing limited progress

OR

More extensive surgery planned

Major bony debridement

30 pre-operative and 10 post operative sessions

III

Stage I or II patient showing limited progress

OR

Pathological fracture, orocutaneous fistulae, evidence of lytic involvement extending to the inferior mandibular border

Major bony debridement and/or reconstructive surgery

30 pre-operative and 10 post operative sessions

PLUS additional 10 after further surgery

 

This protocol and efficacy was further reviewed by Feldmeier and Hampson in 2002 and Annane et al in 2004. Their findings were in favour of HBO for the most part and thus it remains the accepted treatment.

Prophylaxis

Marx has also been key in the development of a treatment protocol for the prevention of ORN in those patients who have been exposed to more than 6800cGy of radiotherapy to the mandibular region. His study shows that those given 20 pre-operative and 10 post operative sessions had better outcomes following the procedure, i.e. less ORN absolute and in those it did occur it was less severe (Marx 1985).

This data was again reviewed by Feldmeier and Hampson (2002) and found to be reproducible.

Research

There are two current multicentre research projects ongoing to further investigate the role of HBO in ORN.

Details of the HOPON trial and participating centres can be found here.

https://www.lctu.org.uk/LCTU_NET/Frontend/Core/Features/TrialInfo.aspx?Data=W1tWSEpwWVd4SGNtOTFjQT09XV1bTVRNPV1bW1ZISnBZV3hKUkE9PV1dW05Eaz1dW1tiRzlqWVd4bF1dW01RPT1d

Details of the DAHANCA-21 trial can be found here.

https://www.lctu.org.uk/LCTU_NET/Frontend/Core/Features/TrialInfo.aspx?Data=W1tWSEpwWVd4SGNtOTFjQT09XV1bTVRNPV1bW1ZISnBZV3hKUkE9PV1dW056az1dW1tiRzlqWVd4bF1dW01RPT1d

 

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 Hyperbaric Oxygen Therapy Indications text has 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, he UHMS Hyperbaric Oxygen Therapy Indications  text has 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(2004) 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.

The HOT2 trial has now completed and the results are currently awaiting publication.

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-high-pressure-oxygen-for-radiotherapy-side-effects

Other Radiation Tissue Injuries

Given the pathological process and the actions of HBO it is reasonable to assume that HBO will have a similar affect 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.

 

To refer a patient please follow this link.

For more information on the patient experience please follow this link.

 

References

The Royal College of Surgeons of Edinburgh

Diploma in Remote and Offshore Medicine

Details found at

http://www.rcsed.ac.uk/education/academic-programmes/remote-and-offshore-medicine/rom-cpd.aspx (Accessed July 2015)

Hyperbaric Oxygen Therapy Indications (2014)

Lindell K, Weaver MD Editors

Undersea and Hyperbaric Medical Society

13th Edition

2014 :P113-138

Annane(2004)

Annane D, Depondt J et al

“Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomised, placebo-controlled, double blind trial from the ORN96 study group.

J Clin Oncol

2004 Dec;22(24):4893-4900

Feldmeier(1998)

Feldmeier JJ, Davolt DA etal

“Histologic morphometry confirms a prophylactic effect for hyperbaric oxygen in the prevention of delayed radiation enteropathy”

Undersea Hyperb Med

1998;25(2):93-97

Feldmeier and Hampson (2002)

Feldmeier JJ, Hampson NB

“A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: an evidence based approach.”

Undersea Hyperb Med

2002;29:4-30

Goldstein(2006)

Goldstein LJ, Gallacher KA, Bauer SM et al

“Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide”

Stem Cells

2006;24:2309-2318

Marx (1985)

Marx RE, Johnson RP, Kline SN

Prevention of osteoradionecrosis: A randomised prospective clinical trial of hyperbaric oxygen versus penicillin

J Am Dent Assoc

1985;11:49-54

Marx (1990)

Marx RE, Ehler WJ, Tayapogsak P, Pierce LW

“Relationship of oxygen dose to angiogenesis induction in irradiated tissue”

Am J Surg

1990;160:519-524

Marx (1999)

Marx RE

“Radiation injury to tissue”

In: Kindwall EP editor

Hyperbaric Medicine Practice 2nd edition

Flagstaff AZ: Best Publishing Company

1999; P 665-723

Parsons (1994)

Parsons  JT

“The effect of radiation on normal tissues of the head and neck”

In: Million RR, Cassisi NJ editors

Management of head and neck cancer: A multidisciplinary approach.

Philadephia, PA;JB Lippincoat

1994: P245-289

 

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