Hyperbaric Oxygen Therapy for Radiation Injuries

Hyperbaric Oxygen Therapy for Radiation Injuries

HBO – What is it? • 100% oxygen is administered to a patient at higher then normal atmospheric pressue. • 2 -2.5 ATA is typical • Treatments average approximately 2 hours.

Domicilium 1662

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

Fontaine’s mobile operating room 1879

French surgeon named J.A. Fontaine built a pressurized mobile operating room.

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

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

Today

Today

Today

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.

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;31:133-45. 2Pasquier D, Hoelscher T, Schmutz J, et al. Radiother Oncol 2004;72:1-13.

Rads & Grays 1 rad = 1 centi Gray (cGy) The effect causes damage to the DNA, lipids, and proteins

Causes cell dysfunction and death

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;59:225-49. 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.

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 radiationinduced necrosis/injury).1

1Feldmeier JJ. Undersea Hyperbaric Med 2004;31:133-45. 2Hunter SE, Scher RL. Curr Opin Otolaryngol Head Neck Surg 2003;11:103-6.

Risk Factors for ORN/STRN Radiation dose1

Trauma or surgery in irradiated area1

Location and size of original tumor1

Risk Factors

Patient age2

Infection in irradiated area1

Prior ischemia (local hypoxia)3

Immunodeficiency1 • Diabetes • Steroids • Immune suppression

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 2007 36:315-20. 3Hoffman KE, Horowitz NS, Russell AH. Gynecol Oncol 2007;106:262-4.

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

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

1.0 ATA Air

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

5 10 15 20 35 40 55

HBO - 2.5 ATA

In hyperbaric conditions, the oxygen tension in the tissues can be up to 280 microns away allowing for a rich collagen matrix to form

50 50 90 120-350 350 Capillary buds invade and form a new vascular network (angiogenesis)-Oxygen tension returns to normal. Wounds can HEAL!

Plateau Phase

Typically after 20 treatments, the new vascular network is laid.

280 300 320 350 Increased oxygen tension allows cells to function normally and aide in healing

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;17:121-30. 2American College of Hyperbaric Medicine. Osteoradionecrosis. 2010. 3Wang J, Boerma M, Fu Q, et al. World J Gastroenterol 2007;13:3047-55.

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”)

Radiation effect on tissues (highest effect to lowest)

Tumor Endothelium Fibroblasts Muscle Nerve

Continues to cause damage to tissues ev after therapy stops Basically obliterates the vessels

Destroys the blood supply to the tissues Leaves tissue hypoxic and very fibrotic (hard, woody tissue)

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)

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)

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.

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

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 0 Frontal

Zygoma

Maxilla

Mandible

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 0 Frontal

Zygoma

Maxilla

Mandible

Clinical Damage Clinical Threshold

Acute

Surgical Trauma

Mechanical Trauma

Subclinical Damage

Years Rubin P, Casarett GW 1968

Nutrition Infection

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 – 1975-2001(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, 1999 www.westegg.com/inflation.

MARX PROTOCOL

2.

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

MARX PROTOCOL

2.

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

MARX PROTOCOL

2.

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

Timing of preoperative HBO therapy is not critical “Delays of up to one year between HBO & surgery have not compromised results”

- Marx 1991

National Cancer Institute Monographs 1990: No 9

"Osteoradionecrosis is best managed with hyperbaric oxygen alone, or in conjunction with surgery" …in high-risk patients, pre-extraction hyperbaric oxygen should be considered

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

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;109:1324-8. 3Delanian S, Depondt J, Lefaix JL. Head Neck 2005;27:114-23.

Complications of Surgery in Irradiated Tissue

DEHISCENCE Control HBO

38 (48%) 4 (11%)

INFECTION Control HBO

Total 19 (24%) 5 ( 6%)

DELAYED HEALING Control HBO

44 (55%) 9 (11%)

Marx RE 1993

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

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

.

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.

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Clark RE et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with longterm follow-up. Int. Journal Radiation Oncology /Biology Phys 2008.

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Undersea and Hyperbaric Board Review course for Physicians. Penn Medicine. August 2010 .

Laryngeal Necrosis • Uncommon complication of radiation therapy for patients with head and neck cancer – usually