Radiation Therapy and the treatment of cancer is often used in conjunction. Hyperbaric Oxygen Therapy should not replace medical protocol, but can assist with alleviating many of radiation’s side effects.
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<strong>American Cancer Society</strong> Complimentary and Alternative Medicine
<strong>Hyperbaric oxygen therapy and cancer—a review</strong> Moen I, Stuhr LE Target Oncol. 2012 Dec;7(4):233-42. doi: 10.1007/s11523-012-0233-x. Epub 2012 Oct 2.
Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO) treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma and thereby increasing O(2) delivery to the tissue.
Studies on HBO and cancer have up to recently focused on whether enhanced oxygen acts as a cancer promoter or not. As oxygen is believed to be required for all the major processes of wound healing, one feared that the effects of HBO would be applicable to cancer tissue as well and promote cancer growth. Furthermore, one also feared that exposing patients who had been treated for cancer, to HBO, would lead to recurrence. Nevertheless, two systematic reviews on HBO and cancer have concluded that the use of HBO in patients with malignancies is considered safe.
To supplement the previous reviews, we have summarized the work performed on HBO and cancer in the period 2004-2012. Based on the present as well as previous reviews, there is no evidence indicating that HBO neither acts as a stimulator of tumor growth nor as an enhancer of recurrence.
On the other hand, there is evidence that implies that HBO might have tumor-inhibitory effects in certain cancer subtypes, and we thus strongly believe that we need to expand our knowledge on the effect and the mechanisms behind tumor oxygenation.
<strong>Patient's perspective on hyperbaric oxygen treatment of osteoradionecrosis</strong><br /> Lee A, Forner L, Jansen EC.<br /> Int J Technol Assess Health Care. 2014 Apr; 30(2):188-93. doi: 10.1017/S0266462314000038. Epub 2014 May 7.
Osteoradionecrosis (ORN) is a known complication to radiation therapy for head and neck cancer with a prevalence of 5-7% among radiated patients. Treatment might include dental surgery and reconstruction of the jawbone as well as hyperbaric oxygen treatment (HBOT). HBOT takes place in a closed compartment where patients are breathing 100% oxygen under pressure for 90 minutes once a day every weekday for 6 weeks. In Denmark, HBOT is available at two facilities with very different organizational set-ups.
<strong>Hyperbaric oxygen pretreatment and preconditioning</strong><br /> Camporesi EM, Bosco G.<br /> Undersea Hyperb Med. 2014 May-Jun;41(3):259-63.
Exposure to hyperbaric oxygen (HBO2) before a crucial event, with the plan to create a preventing therapeutic situation, has been defined “preconditioning” and is emerging as a useful adjunct both in diving medicine as well before ischemic or inflammatory events. Oxygen pre-breathing before diving has been extensively documented in recreational, technical, commercial and military diving for tissue denitrogenation, resulting in reduced post-diving bubble loads, reduced decompression requirements and more rapid return to normal platelet function after a decompression.
Preoxygenation at high atmospheric pressure has also been used in patients before exposure to clinical situations with beneficial effects, but the mechanisms of action have not yet been ascertained. During the reperfusion of ischemic tissue, oxygenated blood increases numbers and activities of oxidants generated in tissues.
Previous reports showed that HBO2 preconditioning caused the activation of antioxidative enzymes and related genes in the central nervous system, including catalase (CAT), superoxide dismutase and heme oxygenase-1.
Despite the increasing number of basic science publications on this issue, studies describing HBO2 preconditioning in the clinical practice remain scarce. To date, only a few studies have investigated the preconditioning effects of HBO2 in relation to the human brain and myocardium with robust and promising results.
<strong>Is there a role for hyberbaric oxygen as primary treatment for grade IV radiation-induced haemorrhagic cystitis? a prospective pilot-feasibility study and review of literature.</strong><br /> Dellis A, Deliveliotis C, Kalentzos V, Vavasis P, Skolarikos A.<br /> Int Braz J Urol. 2014 May-Jun;40(3):296-305. doi: 10.1590/S1677-5538.IBJU.2014.03.02.
PURPOSE: To examine the safety and efficacy of hyperbaric oxygen as the primary treatment for Grade IV radiation-induced haemorrhagic cystitis.
MATERIALS AND METHODS: Hyperbaric oxygen was prospectively applied as a primary treatment option in 11 patients with Grade IV radiation cystitis. Primary endpoint was the incidence of complete and partial response to treatment. Secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival.
RESULTS: All patients completed therapy without complications for a mean follow-up of 17.82 months (range 3 to 34). Mean number of sessions needed was 32.8 (range 27 to 44). Complete and partial response rate was 81.8% and 18.2%, respectively. However, in three patients the first treatment session was not either sufficient or durable giving a 72.7% rate of durable effect.
Interestingly, all 9 patients with complete response received therapy within 6 months of the haematuria onset compared to the two patients with partial response who received therapy at 8 and 10 months from the haematuria onset, respectively (p = 0.018). The need for blood transfusion (p = 0.491) and the total radiation dose (p = 0.259) were not correlated to success-rate. One patient needed cystectomy, while all patients were alive at the end of follow-up.
CONCLUSIONS: Early primary use of hyperbaric oxygen to treat radiation-induced grade IV cystitis is an effective and safe treatment option.
<strong>Hyperbaric oxygen therapy for late radiation tissue injury</strong><br /> Bennett MH, Feldmeier J, Hampson N, Smee R, Milross C.<br /> Cochrane Database Syst Rev. 2012 May 16;5:CD005005. doi: 10.1002/14651858.CD005005.pub3.
BACKGROUND: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of patients having radiotherapy with be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery.
OBJECTIVES: To assess the benefits and harms of HBOT for treating or preventing LRTI.
SEARCH METHODS: In March 2011 we updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 1), MEDLINE, EMBASE, DORCTIHM and reference lists of articles.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing.
DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials.
MAIN RESULTS: Eleven trials contributed to this review (669 participants). For pooled analyses, investigation of heterogeneity suggested important variability between trials but there was some evidence that HBOT is more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P = 0.0002, NNTB = 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse effects.
AUTHORS’ CONCLUSIONS: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected patients and tissues may be justified. Further research is required to establish the optimum patient selection and timing of any therapy. An economic evaluation should be undertaken.
<strong>Limited evidence to demonstrate that the use of hyperbaric oxygen (HBO) therapy reduces the incidence of osteoradionecrosis in irradiated patients requiring tooth extraction</strong><br /> Chuang SK.<br /> J Evid Based Dent Pract. 2012 Sep;12(3 Suppl):248-50. doi: 10.1016/S1532-3382(12)70047-7.
SELECTION CRITERIA: The search covered Medline from January 1948 through March 2008. The subject search by the authors used the following key phrases: Prophylactic hyperbaric oxygen (HBO); preventing osteoradionecrosis (ORN); HBO; ORN; HBO and ORN; HBO, ORN, and dental extractions; HBO and dental extractions; ORN and dental extractions; prophylactic HBO and dental extractions. The authors used EndNote 8.01 (Thomson Reuters, Philadelphia, PA) to perform the search, to import reference data, and to manage the imported references. The electronic search yielded 696 articles. Following further review, which evaluated for compliance to inclusion criteria and data quality, 14 articles were selected for assessment.
KEY STUDY FACTOR: The efficacy of HBO use in irradiated patients.
MAIN OUTCOME MEASURE: The presence of osteoradionecrosis (ORN).
MAIN RESULTS: The authors assessed the quality of the 14 studies in their review using separate criteria for observational studies (cohort and case-control) and for randomizedcontroltrials (RCT). There was only 1RCT among the 14 studies selected. Among the observational studies, 5 articles specified the type of cancer. Among these 6 studies, only 2 studies evaluated patients with nasopharyngeal carcinoma. Another article assessed patients with cancer of the oral cavity, the oropharynx, and the face. Eight articles did not provide any information about the type of cancer.
In 7 of the 14 studies, no HBO was used. Of the remaining 7 that had HBO, 4 used the protocol of Marx et al(1): 20 dives of 90 minutes each, breathing 100% humidified oxygen at 2.4 atm of absolute pressure before surgery, and 10 dives after surgery. Three studies did not mention the specific protocol.
The use of antibiotics as adjunctive therapy was noted in 7 studies: 4 studies used antibiotics preoperatively and postoperatively, and only 3 studies used antibiotics postoperatively. Of the 14 articles, 10 articles reported a definition of ORN. Six articles described ORN as exposed bone that had been irradiated and had been present for 3 to 6 months.
In another study, the bone necrosis was described as developing in 2 forms: minor, as a series of small sequestra that separated spontaneously after periods of weeks or months, and major, where necrosis involved the entire thickness of the jaw with pathologic fracture inevitable. Information provided on the method of extraction used was limited, with only 3 of the 14 reports stating the method (nonsurgical or atraumatic extraction). Primary closure was attempted or used in 3 studies, whereas 2 noted that primary closure was not used. Five studies did not indicate either the method of extraction or whether there was primary closure.
The only one randomized, prospective, controlled trial in this systematic review-Marx et al(1)-compared the incidence of ORN in head-and neck-irradiated patients who required dental extractions. They had 2 groups: one group received prophylactic HBO, whereas the other group received antibiotics. The HBO group had a lower incidence of ORN compared with the antibiotic group (5.4% vs 29.9%). In the cohort and observational studies, the occurrence rate of ORN in the prophylactic HBO patients was in the range from 0% to 11% (median, 4.1%), whereas in the non-HBO patients the range was from 0% to 29.9% (median, 7.1%).
CONCLUSIONS: The systematic review by the authors did not identify any reliable evidence to either support or refute the efficacy of HBO in the prevention of postextraction ORN to irradiated patients. As a result, additional controlled clinical trials will be needed to address this important question.
<strong>A practical guide for patients undergoing exodontia following radiotherapy to the oral cavity</strong><br /> Kanatas AN, Rogers SN, Martin MV.<br /> Dent Update. 2002 Dec;29(10):498-503.
Dental extractions or minor oral surgery in patients who have undergone radiation therapy for cancer in the head and neck carry the risk of one of the most serious and devastating complications of head and neck radiotherapy, that of osteoradionecrosis (ORN). A totally unified approach to dental extractions following radiotherapy is lacking.
The role of the general dental practitioner in management of patients following radiotherapy is crucial. Contrary to clinical impression, the risk of ORN does not decrease with time. When contemplating exodontia or minor oral surgery in the irradiated patient, special consideration should be given to issues such as radiotherapy history, surgical assessment, surgical procedure and the role of antibiotics and hyperbaric oxygen.
<strong>Hyperbaric oxygen therapy and osteoradionecrosis</strong><br /> Porter BR, Brian JE Jr.<br /> Iowa Dent J. 1999 Jul;85(3):23-7.
Osteoradionecrosis of the mandible is a potentially devastating complication of head and neck radiation. Radiation causes progressive vascular occlusion with tissue hypoxia, tissue death, and failure of healing. Hyperbaric oxygen therapy is an accepted treatment for osteoradionecrosis. This article reviews the history of hyperbaric oxygen therapy, its physiologic mechanisms, its use in the management of osteoradionecrosis, and its complications and contraindications.
<strong>Hyperbaric oxygen in the prevention of osteoradionecrosis of the jaws</strong><br /> Vudiniabola S, Pirone C, Williamson J, Goss AN.<br /> Aust Dent J. 1999 Dec;44(4):243-7.
Patients who have had their jaws irradiated as part of management of head and neck malignancy are at risk of osteoradionecrosis (ORN) following tooth extraction. Thirty-seven patients with a history of irradiation to the jaws were managed during a four year period.
Twenty-nine patients received hyperbaric oxygen therapy (HBO) consisting of 20 treatments before surgery and ten treatments after. Only one (4 per cent) developed ORN. Seven patients who did not have HBO and one who did (15 per cent) developed ORN.
The need for prophylactic treatment with HBO is discussed. It is recommended that prophylactic HBO is used prior to surgery for irradiated facial bones.
<strong>A review of the Marx protocols: prevention and management of osteoradionecrosis by combining surgery and hyperbaric oxygen therapy</strong><br /> Cronje FJ.<br /> SADJ. 1998 Oct; 53(10):469-71.
The 30/10 protocol is employed in the treatment of established osteoradionecrosis. No surgery should be attempted before the first 30 HBO treatments have provided sufficient angiogenesis to support surgical wounding.
After 30 treatments surgical management can be staged according to the extent of improvement achieved after HBO and the size of sequestrum or area of osteolysis. If the ORN extends to the inferior border of the mandible or if it manifests as an orocutaneous fistula or pathological fracture, discontinuity resection of the necrotic bone and soft tissue will be required to resolve the disease.
Unless HBO and surgery are combined in the management of ORN, the results are not long lasting or satisfactory. Even though resection of stage three ORN seems unduly aggressive, it has stood the test of time.
By using the Marx protocols in the treatment of ORN, more than 95 per cent of patients can be successfully cured of their disease with predictable, functional and aesthetically acceptable outcomes.
<strong>Osteoradionecrosis: causes and prevention</strong><br /> Friedman RB.<br /> NCI Monogr. 1990;(9):145-9.
Osteoradionecrosis (ORN) is one of the most serious complications arising from head and neck radiation therapy.
Current research has shown that ORN represents nonhealing, dead bone and is not a state of infection. ORN is the result of functional and structural bony changes that may not be expressed for months or years. ORN may occur spontaneously or in response to wounding. Predisposing factors include absorbed radiation dose, fractionation, delivery modality, and dental status. Timing of dental extractions and other factors have also been shown to affect incidence. ORN may be reduced through early intraoral evaluation, treatment, and adequate healing time prior to beginning RT.
Hyperbaric oxygen (HBO) therapy has been beneficial in the prevention and treatment of ORN. It is of paramount importance for the medical community to recognize the factors that may reduce ORN incidence, endorse oral care protocols, and acknowledge the value of HBO therapy in the prevention and treatment of this disease.