1. Hyperbaric Oxygen Therapy for Radiation Injuries

2. HBO – What is it?
100% oxygen is administered to a patient at higher then normal atmospheric pressue.
ATA is typical
Treatments average approximately 2 hours.

3. Domicilium 1662
Henshaw, British clergyman built a sealed chamber called a Domicilium. (O2 discovered 1775).

4. Fontaine’s mobile operating room 1879
French surgeon named J.A. Fontaine built a pressurized mobile operating room.

5. Cunningham’s chamber in 1921
Orville J. Cunningham, a professor at the University of Kansas built a chamber that was 10 feet in diameter and 88 feet in length

6. Steel Ball Hospital 1928 .
However, one patient that Cunningham treated, Mr Timkin of the Timkin Rollerbearing Company, felt that the time he spent in Cunningham's chamber cured his uremia. In 1928 as a show of gratitude, Timkin built a steel sphere, which was 6 stories tall, and 64 feet in diameter, the largest hyperbaric chamber ever built. Cunningham used this hospital, located in Cleveland, to treat patients with a number of ailments. It was well appointed, with dining rooms, private patient rooms, plush carpets, and even a smoking room on the top floor! Without any scientific rationale for his work, he was forced to close down by the AMA and the Cleveland Medical Society in 1930, and the steel ball hospital was cut up for scrap during World War II. This essentially ended the era of compressed-air hyperbaric therapy

7. Today

8. Today

9. Today

10. UHMS INDICATIONS 1. Air or Gas Embolism.
2. Carbon Monoxide Poisoning/Cyanide Poisoning.
3. Clostridial Myositis and Myonecrosis (Gas Gangrene).
4. Crush Injury, Compartment Syndrome and other Acute Traumatic
Ischemia’s.
5. Decompression Sickness.
6. Arterial Insufficiencies – Enhancement of Healing in Selected Problem
Wounds and Central Retinal Artery Occlusion.
7. Severe Anemia.
8. Intracranial Abscess.
9. Necrotizing Soft Tissue Infections.
10. Osteomyelitis (Refractory).
11. Delayed Radiation Injury (Soft Tissue and Bony Necrosis).
12. Compromised Grafts and Flaps.
13. Acute Thermal Burn Injury.
14. Idiopathic Sudden Sensorineural Hearing Loss.

11. Definition: Radiation Tissue Injuries
Radiation injuries can be divided into two categories on a time basis:
Acute injuries are those that present shortly after irradiation—generally within weeks1
Osteoradionecrosis and soft tissue radionecrosis are those conditions that present several months or even years after irradiation.1,2
1Feldmeier JJ. Undersea Hyperbaric Med 2004;31:
2Pasquier D, Hoelscher T, Schmutz J, et al. Radiother Oncol 2004;72:1-13.

12. Radiation Dosing Rads & Grays 1 rad = 1 centi Gray (cGy)
The effect causes damage to the DNA, lipids, and proteins
Causes cell dysfunction and death

13. Incidence of ORN and STRN
The incidence of osteoradionecrosis (ORN) and soft tissue radionecrosis (STRN) is not known with any certainty
In the U.S., approximately 1.5 million new cancer cases are diagnosed every year1
Data suggest that 750,000 patients with cancer receive radiotherapy every year, and if two-thirds are long-term survivors and 10% of these patients experience ORN or STRN in their lifetime,2,3 this would be about 50,000 individuals per year (0.017% of U.S. population)
Another way of looking at the statistics: More than 200,000 patients receive abdominal or pelvic radiation therapy each year, and there are approximately 1.7 million survivors of this treatment who have or have had intestinal dysfunction as a result of STRN.4
1Jemal A, Siegel R, Ward E, et al. CA Cancer J Clin 2009;59:
2Feldmeier JJ, Hampson NB. Undersea Hyperb Med 2002;29:4-30.
3Rubin P, Casarrett GW. Clinical Radiation Pathology. Vol 1. Philadelphia: WB Saunders, 1968:58-61.
4Hauer-Jensen M, Wang J, Boerma M, et al. Curr Opin Support Palliat Care 2007;1:23-9.

14. ORN/STRN Tissue Injury Sites
Where can ORN or STRN occur?
Any tissue that has been irradiated!
Jaw (osteoradionecrosis; inadequate bone repair)1
Neck area (e.g., chondroradionecrosis of the larynx)2
Chest wall radionecrosis (result of treatment for breast, lung, or esophageal cancers)1
Hemorrhagic radiation-induced cystitis1
Chronic radiation-induced proctitis/enteritis1
Spinal cord, brain, optic nerve, brachial plexus (myelitis or radiation-induced necrosis/injury).1
1Feldmeier JJ. Undersea Hyperbaric Med 2004;31:
2Hunter SE, Scher RL. Curr Opin Otolaryngol Head Neck Surg 2003;11:103-6.

15. Risk Factors for ORN/STRN
Radiation dose1
Location and size of original tumor1
Risk Factors
Infection in irradiated area1
Trauma or surgery in irradiated area1
Prior ischemia
(local hypoxia)3
Immunodeficiency1
Diabetes
Steroids
Immune suppression
Patient age2
1Chrcanovic BR, Reher P, Sousa AA, et al. Oral Maxillofac Surg 2010;14:3-16.
2Lye KW, Wee J, Gao F, et al. Int J Oral Maxillofac Surg :
3Hoffman KE, Horowitz NS, Russell AH. Gynecol Oncol 2007;106:262-4.

16. Tissue Oxygen Levels Needed for Healing
Tissues require oxygen to survive
We can measure tissue oxygenation levels with a TcPo2
A minimum of 20 mmhg partial pressure of oxygen is required for cells that aide in wound healing (fibroblast proliferation and collagen production) to function
Levels are far below this 20 mmhg in tissue that has received radiation

17. HBO stimulates collagen synthesis, vascular networking, metabolism of bone, and may increase stem cells.

18. In normal tissue in normobaric (room air or 1 ata) conditions, the tension of oxygen in the tissues is only 30 microns away from the damaged capillary wall
1.0 ATA Air

19. In hyperbaric conditions, the oxygen tension in the tissues can be up to 280 microns away allowing for a rich collagen matrix to form
HBO ATA
Capillary buds invade and form a new vascular network (angiogenesis)-- Oxygen tension returns to normal. Wounds can HEAL!

20. Typically after 20 treatments, the new vascular network is laid.
Plateau Phase
Increased oxygen tension allows cells to function normally and aide in healing

21. General Causes of ORN/STRN
ORN or STRN actually begins when radiation is first given1
Levels of pro-inflammatory cytokines rise (e.g., IL-1, IL-6, TNF-alpha)
In some cases, the levels of cytokines associated with inflammatory actions stay elevated leading to further injury
The levels of these same cytokines may subside but the cytokines may be affected later by another surgery, trauma, or infection years later.
Radiation causes the lining of small blood vessels to become inflamed and then occluded, leading to tissue ischemia2
Some researchers postulate increased thrombin levels and vascular permeability with subsequent fibrin and collagen deposition between cells. Fibrosis, dysfunction, and even obliteration of the local vasculature (especially capillaries) then follow.3
1Brush J, Lipnick SL, Phillips T, et al. Semin Radiat Oncol 2007;17:
2American College of Hyperbaric Medicine. Osteoradionecrosis
3Wang J, Boerma M, Fu Q, et al. World J Gastroenterol 2007;13:

22. Pattern of Injury to Tissues
Tumor - treated as a mass of cells
A boost dose of radiation is given to the center of this mass of cells
The further away from the center of that mass, the less the dose of radiation
Additional injury can occur to tissues around the mass of cells (called a “diffusion injury”)

23. Radiation Effects Tumor Endothelium Fibroblasts Muscle Nerve
Radiation effect on tissues (highest effect to lowest)
Tumor
Endothelium
Fibroblasts
Muscle
Nerve

24. RADIATION
Continues to cause damage to tissues even after therapy stops
Basically obliterates the vessels
Destroys the blood supply to the tissues
Leaves tissue hypoxic and very fibrotic (hard, woody tissue)

25. Early (acute) Effects to the skin
Radiation Effects
Early (acute) Effects to the skin
Redness (erythema)
Changes in the pigment of the skin
Hair loss
Skin erosion
Supportive care
Antibiotics if skin tissues become infected (cellulitis)

26. Delayed Effects of Radiation
Radiation Effects
Delayed Effects of Radiation
Typically seen after 6 months and up to years later
Endarteritis (inflammation of the lining of the artery is what causes the problem)

27. Radiation Effects
It is difficult to provide adequate nutrients & oxygen to tissues without a good blood supply. This leads to delayed healing.
There is no satisfactory treatment of radiation necrosis using conventional therapies. HBO is the only intervention that has shown to increase the number of blood vessels in irradiated tissue.

28. Radiation Effects to Bone
Bone is 1.8 x more denes than soft tissues so it absorbs more of the radiation energy
Radiation affects both the vascular & cellular components of bone.
Mandible (jaw) is very susceptible
– greater bone density & lower vascularity

29. Blood flow in bone that has NOT received radiation
Granstrom G 1993 XIXth Annual EUBS Meeting
ml/mg x 100g tissue 14 12 10 8 6 4 2
Frontal Zygoma Maxilla Mandible

30. Blood flow in bone that HAS received radiation
Granstrom G 1993 XIXth Annual EUBS Meeting
ml/mg x 100g tissue 14 12 10 8 6 4 2
Frontal Zygoma Maxilla Mandible

31. Osteoradionecrosis vs Time
Clinical Damage
Clinical
Threshold
Acute
Surgical Trauma
Mechanical Trauma
Nutrition Infection
Subclinical
Damage
Recovery
After the patient recovers from the acute effects of radiation (if they recover), the late effects can occur either spontaneously or through trauma.
89% of cases looked at in one Marx study were induced by trauma
Trauma includes Surgery in the area that received radiation
Mechanical trauma (like chewing)
Or nutritional defects that lead to infection (or visa versa)
11% of the problems were spontaneous.
H B O
Years
Rubin P, Casarett GW 1968 31

32. OSTEORADIONECROSIS of the mandible (ORN)
Incidence 0% below 6,000 cGy,1.8% 6,000-7,000 cGy, and 9% >7,000 cGy.
Pathophysiology – hypoxia, hypovascularity, and hypocellularity.
Marx Protocol – prophylaxis, stages 1-111R all at 2.5 ATA for 90 minutes.
Evidence – (14 case series using HBO and surgery) – 13/14 found benefit and 86% patients improved.
Cost saving in 2006 – $168,000 without HBO and $53,000 with HBO.
Feldmeier JJ, Hampson NB: Undersea Hyperbaric Med 2002, Marx RE,

33. MARX PROTOCOL2.
Osteoradionecrosis is defined as the presence of exposed bone without healing. Marx creating staging according to wound healing treatment and hyperbaric oxygen response.
Stage I (A): Chronically exposed bone or rapidly progressive ORN without any serious manifestations found in stage III. 30 HBO presurgical treatments followed by minor bony debridement followed by 10 HBO postsurgical treatments.
1Marx RE. J Oral Maxillofac Surg .
1983;41:352-7.
2American College of Hyperbaric Medicine. Osteoradionecrosis. 2010

34. MARX PROTOCOL2.
Stage II – If patients are not progressing appropriately at 30 HBO at Stage I or if they are needing more major debridement, they are advanced to this stage and receive a more radical surgical debridement in the OR followed by 10 post-surgical HBO treatments. Surgery must maintain mandibular continuity. If mandibular resection is required they are advanced to Stage III.
1Marx RE. J Oral Maxillofac Surg .
1983;41:352-7.
2American College of Hyperbaric Medicine. Osteoradionecrosis. 2010

35. MARX PROTOCOL2.
In addition to those failing treatment in Stage I and II, grave prognostic signs such as pathologic fracture, orocutaneous fistulae or lytic involvement extending to the inferior mandibular border. Mandibular resection is part of the treatment plan. Patients receive 30 HBO pre-surgical treatments and 10 HBO post-surgical treatments.
1Marx RE. J Oral Maxillofac Surg .
1983;41:352-7.
2American College of Hyperbaric Medicine. Osteoradionecrosis. 2010

36. Prevention of Osteoradionecrosis
Timing of preoperative HBO therapy is not critical
“Delays of up to one year between HBO & surgery
have not compromised results” O 2
- Marx 1991

37. "Osteoradionecrosis is best managed
National Cancer Institute Monographs 1990: No 9
"Osteoradionecrosis is best managed
with hyperbaric oxygen alone, or in
conjunction with surgery" 2
…in high-risk patients, pre-extraction hyperbaric oxygen should be considered

38. HBO and ORN
There have been 22 studies published that show hyperbarics is useful either alone or as an adjunctive therapy
Improvement has been show in 78% of these cases Hyperbarics has also shown to be useful in preventing or reducing complications if done prior to surgical intervention

39. Conventional Treatment of ORN
Nutritional support is essential as many patients become nutritionally deficient1
Antibiotics where infection is suspected1
Debridement to remove sequestra where identified2
Microvascular free tissue transfer for stage III patients and jaw resection as necessary.2
There have been reports of treating stage I patients with pentoxifylline (to improve blood flow), bisphosphonates, and vitamin E, but success to date must be regarded as preliminary.3
1Blanchaert Jr RH, Harris CM. eMedicine 2010.
1Hao SP, Chen HC, Wei FC, et al. Laryngoscope 1999;109:
3Delanian S, Depondt J, Lefaix JL. Head Neck 2005;27:

40. DEHISCENCE INFECTION DELAYED HEALING Total
Complications of Surgery in Irradiated Tissue
DEHISCENCE
38 (48%)
4 (11%)
Control
HBO
INFECTION
Total
19 (24%)
5 ( 6%)
Control
HBO
In this Marx study in the HBO Group , you can see that there were far less instances of these three complications
DELAYED HEALING
44 (55%)
9 (11%)
Control
HBO
Marx RE 1993 40

42. Soft Tissue Radionecrosis
RADIATION INJURY
Soft Tissue Radionecrosis
Radiation Cystitis
Radiation Proctitis
Laryngeal Radionecrosis
Chest Wall Radionecrosis
Abdominal and Pelvic Radionecrosis
Radiation injuries of the extremities
Neurologic Injuries Secondary to Radiation

43. Indication of HBO Delayed Radiation Injuries
RADIATION CYSTITIS
Symptoms include - hematuria, nocturia, frequency and or urgency.
18/20 published reports showed significant improvement or resolution in 76%.
Undersea and Hyperbaric Board Review course for physicians – Penn Medicine Aug 2010.

44. Indication of HBO Delayed Radiation Injuries
RADIATION PROCTITIS
Symptoms include – rectal bleeding/pain, diarrhea, and tenesmus.
Combined results from trials including a total of 199 cases – complete resolution in 41% and 86% had at least partial response.
Clark RE et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. Int. Journal Radiation Oncology /Biology Phys 2008.
Undersea and Hyperbaric Board Review course for Physicians. Penn Medicine. August 2010.

45. Laryngeal Necrosis
Uncommon complication of radiation therapy for patients with head and neck cancer – usually <1%.
Often present with persistent edema, fetid breath, and or visible necrosis.
Chandler grade 1-4 (1 and 2 usually resolve).
5 published reports – out of 43 patients, only 6 failed and required a laryngectomy, the other 37 maintained their voice box and good voice quality with HBO.
Hyperbaric Oxygen Therapy Indications. 12th edition.

46. RADIATION INJURIES

47. ONCERNS Does HBO cause cancer or make cancer worse?
Extensive review of clinical and animal studies showed no enhancement of cancer growth.
Hyperbaric Oxygen Therapy Indications 12th edition. 47

48. Summary
HBO for the late effects of radiation is supported by Prospective Randomized Trials
Deemed to be a “Standard of Care” by the National Cancer Institute
The weight of current evidence favors use of HBO
Demonstrated “financial” effectiveness
No proven alternative therapies

49. REFERENCES G, LB. HYPERBARIC OXYGEN THERAPY INDICATIONS. 12TH EDITION.
KINDWALL, EP., WHELAN, HT. HYPERBARIC MEDICINE PRACTICE. 3RD EDITION.
HEALOGICS – WOUND CARE CENTERS.