Presentation on theme: "Hyperbaric Oxygen Therapy for Radiation Injuries"— Presentation transcript:
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 typicalTreatments average approximately 2 hours.
3 Domicilium 1662Henshaw, 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
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 TraumaticIschemia’s.5. Decompression Sickness.6. Arterial Insufficiencies – Enhancement of Healing in Selected ProblemWounds 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 weeks1Osteoradionecrosis and soft tissue radionecrosis are those conditions that present several months or even years after irradiation.1,21Feldmeier 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 proteinsCauses 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 certaintyIn the U.S., approximately 1.5 million new cancer cases are diagnosed every year1Data 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.41Jemal 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)1Neck area (e.g., chondroradionecrosis of the larynx)2Chest wall radionecrosis (result of treatment for breast, lung, or esophageal cancers)1Hemorrhagic radiation-induced cystitis1Chronic radiation-induced proctitis/enteritis1Spinal cord, brain, optic nerve, brachial plexus (myelitis or radiation-induced necrosis/injury).11Feldmeier 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 dose1Location and size of original tumor1Risk FactorsInfection in irradiated area1Trauma or surgery in irradiated area1Prior ischemia(local hypoxia)3Immunodeficiency1DiabetesSteroidsImmune suppressionPatient age21Chrcanovic 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 surviveWe can measure tissue oxygenation levels with a TcPo2A minimum of 20 mmhg partial pressure of oxygen is required for cells that aide in wound healing (fibroblast proliferation and collagen production) to functionLevels 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 wall1.0 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 formHBO ATACapillary 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 PhaseIncreased 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 given1Levels 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 injuryThe 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 ischemia2Some 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.31Brush J, Lipnick SL, Phillips T, et al. Semin Radiat Oncol 2007;17:2American College of Hyperbaric Medicine. Osteoradionecrosis3Wang J, Boerma M, Fu Q, et al. World J Gastroenterol 2007;13:
22 Pattern of Injury to Tissues Tumor - treated as a mass of cellsA boost dose of radiation is given to the center of this mass of cellsThe further away from the center of that mass, the less the dose of radiationAdditional 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)TumorEndotheliumFibroblastsMuscleNerve
24 RADIATIONContinues to cause damage to tissues even after therapy stopsBasically obliterates the vesselsDestroys the blood supply to the tissuesLeaves tissue hypoxic and very fibrotic (hard, woody tissue)
25 Early (acute) Effects to the skin Radiation EffectsEarly (acute) Effects to the skinRedness (erythema)Changes in the pigment of the skinHair lossSkin erosionSupportive careAntibiotics if skin tissues become infected (cellulitis)
26 Delayed Effects of Radiation Radiation EffectsDelayed Effects of RadiationTypically seen after 6 months and up to years laterEndarteritis (inflammation of the lining of the artery is what causes the problem)
27 Radiation EffectsIt 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 energyRadiation 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 Meetingml/mg x 100g tissue1412108642Frontal Zygoma Maxilla Mandible
30 Blood flow in bone that HAS received radiation Granstrom G 1993 XIXth Annual EUBS Meetingml/mg x 100g tissue1412108642Frontal Zygoma Maxilla Mandible
31 Osteoradionecrosis vs Time Clinical DamageClinicalThresholdAcuteSurgical TraumaMechanical TraumaNutrition InfectionSubclinicalDamageRecoveryAfter 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 traumaTrauma includes Surgery in the area that received radiationMechanical trauma (like chewing)Or nutritional defects that lead to infection (or visa versa)11% of the problems were spontaneous.H B OYearsRubin P, Casarett GW 196831
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, 1999
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 & surgeryhave not compromised results”O2- Marx 1991
37 "Osteoradionecrosis is best managed National Cancer Institute Monographs 1990: No 9"Osteoradionecrosis is best managedwith hyperbaric oxygen alone, or inconjunction with surgery"2…in high-risk patients, pre-extraction hyperbaric oxygen should be considered
38 HBO and ORNThere have been 22 studies published that show hyperbarics is useful either alone or as an adjunctive therapyImprovement 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 deficient1Antibiotics where infection is suspected1Debridement to remove sequestra where identified2Microvascular free tissue transfer for stage III patients and jaw resection as necessary.2There 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.31Blanchaert 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 TissueDEHISCENCE38 (48%)4 (11%)ControlHBOINFECTIONTotal19 (24%)5 ( 6%)ControlHBOIn this Marx study in the HBO Group , you can see that there were far less instances of these three complicationsDELAYED HEALING44 (55%)9 (11%)ControlHBOMarx RE 199340
42 Soft Tissue Radionecrosis RADIATION INJURYSoft Tissue RadionecrosisRadiation CystitisRadiation ProctitisLaryngeal RadionecrosisChest Wall RadionecrosisAbdominal and Pelvic RadionecrosisRadiation injuries of the extremitiesNeurologic Injuries Secondary to Radiation
43 Indication of HBO Delayed Radiation Injuries RADIATION CYSTITISSymptoms 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 PROCTITISSymptoms 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 NecrosisUncommon 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.
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 SummaryHBO for the late effects of radiation is supported by Prospective Randomized TrialsDeemed to be a “Standard of Care” by the National Cancer InstituteThe weight of current evidence favors use of HBODemonstrated “financial” effectivenessNo proven alternative therapies