Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on 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 complications following surgery and radiotherapy. OBJECTIVES: To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. ADVERSE EVENTS: Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

Physiologic and biochemical rationale for treating COVID-19 patients with hyperbaric oxygen.

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world's population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.

Hyperbaric oxygen is still needed in the management and prevention of mandibular necrosis: a response to Mr. Richard Clarke.

Mr. Richard Clarke presents in this Journal his arguments against continued application of hyperbaric oxygen (HBO2) therapy to the pre-extraction neoadjuvant treatment or the treatment of frank mandibular ORN. In the same article he advocates a promising renewed interest in HBO2 as a radiosensitizer. Arguments against HBO2 prior to extractions are based on several papers which consistently include low-risk patients. The just-released HOPON trial reports a negative pre-extraction outcome for HBO2, but patients were enrolled with radiation doses as low as 50Gy. For advanced mandibular necrosis (Marx Stage III) requiring resection, fibular free flap reconstruction is advocated. A high complication rate with free flaps is acknowledged but the magnitude of these complications is not discussed. A cost savings for this procedure is suggested, but no mention is made of the typical cost of the procedure ($90,000) or the requirement of a typical one-week hospital stay, including an initial one or two days in the ICU. Nor is mention made of the very low rate of subsequent dental rehabilitation. The success reported by Delainian, et al. employing pentoxifylline, Vitamin E and sometimes a bisphosphonate is equated to the four decades of HBO2 success with the Marx protocol for Stage I and II ORN. In the phase II trial by Delainian (not randomized) six of her 54 patients died secondary to sepsis, and she graded patients as complete responders if 5mm or less bone was exposed. Even at entry patients had an average of only 1.7 cm exposed bone and treatment was prolonged (16 + or -9 months). Any cost comparison studies will have to account for the indirect expenses of this prolonged treatment including lost productivity.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and harms of administering radiotherapy for the treatment of malignant tumours while breathing HBO. SEARCH METHODS: In September 2017 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library Issue 8, 2017, MEDLINE, Embase, and the Database of Randomised Trials in Hyperbaric Medicine using the same strategies used in 2011 and 2015, and examined the reference lists of included articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air or an alternative sensitising agent. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of and extracted data from the included trials. MAIN RESULTS: We included 19 trials in this review (2286 participants: 1103 allocated to HBOT and 1153 to control).For head and neck cancer, there was an overall reduction in the risk of dying at both one year and five years after therapy (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98, number needed to treat for an additional beneficial outcome (NNTB) = 11 and RR 0.82, 95% CI 0.69 to 0.98, high-quality evidence), and some evidence of improved local tumour control immediately following irradiation (RR with HBOT 0.58, 95% CI 0.39 to 0.85, moderate-quality evidence due to imprecision). There was a lower incidence of local recurrence of tumour when using HBOT at both one and five years (RR at one year 0.66, 95% CI 0.56 to 0.78, high-quality evidence; RR at five years 0.77, 95% CI 0.62 to 0.95, moderate-quality evidence due to inconsistency between trials). There was also some evidence with regard to the chance of metastasis at five years (RR with HBOT 0.45 95% CI 0.09 to 2.30, single trial moderate quality evidence imprecision). No trials reported a quality of life assessment. Any benefits come at the cost of an increased risk of severe local radiation reactions with HBOT (severe radiation reaction RR 2.64, 95% CI 1.65 to 4.23, high-quality evidence). However, the available evidence failed to clearly demonstrate an increased risk of seizures from acute oxygen toxicity (RR 4.3, 95% CI 0.47 to 39.6, moderate-quality evidence).For carcinoma of the uterine cervix, there was no clear benefit in terms of mortality at either one year or five years (RR with HBOT at one year 0.88, 95% CI 0.69 to 1.11, high-quality evidence; RR at five years 0.95, 95% CI 0.80 to 1.14, moderate-quality evidence due to inconsistency between trials). Similarly, there was no clear evidence of a benefit of HBOT in the reported rate of local recurrence (RR with HBOT at one year 0.82, 95% CI 0.63 to 1.06, high-quality evidence; RR at five years 0.85, 95% CI 0.65 to 1.13, moderate-quality evidence due to inconsistency between trials). We also found no clear evidence for any effect of HBOT on the rate of development of metastases at both two years and five years (two years RR with HBOT 1.05, 95% CI 0.84 to 1.31, high quality evidence; five years RR 0.79, 95% CI 0.50 to 1.26, moderate-quality evidence due to inconsistency). There were, however, increased adverse effects with HBOT. The risk of a severe radiation injury at the time of treatment with HBOT was 2.05, 95% CI 1.22 to 3.46, high-quality evidence. No trials reported any failure of local tumour control, quality of life assessments, or the risk of seizures during treatment.With regard to the treatment of urinary bladder cancer, there was no clear evidence of a benefit in terms of mortality from HBOT at one year (RR 0.97, 95% CI 0.74 to 1.27, high-quality evidence), nor any benefit in the risk of developing metastases at two years (RR 2.0, 95% CI 0.58 to 6.91, moderate-quality evidence due to imprecision). No trial reported on failure of local control, local recurrence, quality of life, or adverse effects.When all cancer types were combined, there was evidence for an increased risk of severe radiation tissue injury during the course of radiotherapy with HBOT (RR 2.35, 95% CI 1.66 to 3.33, high-quality evidence) and of oxygen toxic seizures during treatment (RR with HBOT 6.76, 96% CI 1.16 to 39.31, moderate-quality evidence due to imprecision). AUTHORS' CONCLUSIONS: We found evidence that HBOT improves local tumour control, mortality, and local tumour recurrence for cancers of the head and neck. These benefits may only occur with unusual fractionation schemes. Hyperbaric oxygenation therapy is associated with severe tissue radiation injury. Given the methodological and reporting inadequacies of the included studies, our results demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for uterine cervical or bladder cancer. There is little evidence available concerning malignancies at other anatomical sites.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of people having radiotherapy will 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: We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11), MEDLINE, EMBASE, DORCTIHM and reference lists of articles in December 2015. We also searched for ongoing trials at clinicaltrials.gov. 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: Fourteen trials contributed to this review (753 participants). There was some moderate quality evidence that HBOT was more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P value = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5; 246 participants, 3 studies). There was also moderate quality evidence of a significantly improved chance of wound breakdown without HBOT following operative treatment for ORN (RR 4.2; 95% CI 1.1 to 16.8, P value = 0.04, NNTB 4; 264 participants, 2 studies). 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 value = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P value = 0.0002, NNTB 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P value = 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 value = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no randomised data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse events. 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 participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.

Hyperbaric oxygen therapy for late radiation tissue injury.

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.

Dosimetric and thermal properties of a newly developed thermobrachytherapy seed with ferromagnetic core for treatment of solid tumors.

PURPOSE: Studies of the curative effects of hyperthermia and radiation therapy on treatment of cancer show a strong evidence of a synergistic enhancement when both radiation and hyperthermia modalities are applied simultaneously. Varieties of tissue heating approaches developed up to date still fail to overcome such essential limitations as an inadequate temperature control, temperature nonuniformity, and prolonged time delay between hyperthermia and radiation treatments. The authors propose a new self-regulating thermobrachytherapy seed, which serves as a source of both radiation and heat for concurrent administration of brachytherapy and hyperthermia. METHODS: The proposed seed is based on the BEST Medical, Inc., Seed Model 2301-I(125), where tungsten marker core and the air gap are replaced with a ferromagnetic material. The ferromagnetic core produces heat when subjected to alternating electromagnetic (EM) field and effectively shuts off after reaching the Curie temperature (T(C)) of the ferromagnetic material thus realizing the temperature self-regulation. The authors present a Monte Carlo study of the dose rate constant and other TG-43 factors for the proposed seed. For the thermal characteristics, the authors studied a model consisting of 16 seeds placed in the central region of a cylindrical water phantom using a finite-element partial differential equation solver package "COMSOL Multiphysics." RESULTS: The modification of the internal structure of the seed slightly changes dose rate and other TG-43 factors characterizing radiation distribution. The thermal modeling results show that the temperature of the thermoseed surface rises rapidly and stays constant around T(C) of the ferromagnetic material. The amount of heat produced by the ferromagnetic core is sufficient to raise the temperature of the surrounding phantom to the therapeutic range. The phantom volume reaching the therapeutic temperature range increases with increase in frequency or magnetic field strength. CONCLUSIONS: An isothermal distribution matching with the radiation isodose distribution can be achieved within a target volume by tuning frequency and intensity of the alternating magnetic field. The proposed combination seed model has a potential for implementation of concurrent brachytherapy and hyperthermia.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and harms of radiotherapy while breathing HBO. SEARCH METHODS: In March 2011 we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 3), MEDLINE, EMBASE, DORCTHIM and reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of the relevant trials and extracted the data from the included trials. MAIN RESULTS: Nineteen trials contributed to this review (2286 patients: 1103 allocated to HBOT and 1153 to control). With HBOT, there was a reduction in mortality for head and neck cancers at both one year and five years after therapy (risk ratio (RR) 0.83, P = 0.03, number needed to treat (NNT) = 11; and RR 0.82, P = 0.03, NNT = 5 respectively), as well as improved local tumour control at three months (RR with HBOT 0.58, P = 0.006, NNT = 7). The effect of HBOT varied with different fractionation schemes. Local tumour recurrence was less likely with HBOT at one year (head and neck: RR 0.66, P < 0.0001, NNT = 5), two years (uterine cervix: RR 0.60, P = 0.04, NNT = 5) and five years (head and neck: (RR 0.77, P = 0.01, NNT = 6). Any advantage is achieved at the cost of some adverse effects. There was a significant increase in the rate of both severe radiation tissue injury (RR 2.35, P < 0.0001, (number needed to harm (NNH) = 8) and the chance of seizures during therapy (RR 6.76, P = 0.03, NNH = 22) with HBOT. AUTHORS' CONCLUSIONS: There is some evidence that HBOT improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the head and neck, and uterine cervix. These benefits may only occur with unusual fractionation schemes. HBOT is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury. The methodological and reporting inadequacies of the studies included demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other anatomical sites on which to base a recommendation.

Hyperbaric oxygen therapy and delayed radiation injuries (soft tissue and bony necrosis): 2012 update.

Informal surveys at CME meetings have shown that approximately one-third of patients in the United States receive hyperbaric oxygen (HBO2) for delayed radiation injury. More than 600,000 patients receive radiation for malignancy in our country annually, and about one-half will be long-term survivors. Serious radiation complications occur in 5-10% of survivors. A large population of patients is therefore at risk for radiation injury. HBO2 has been applied to treat patients with radiation injury since the mid-1970s. Published results are consistently positive, but the level of evidence for individual publications is usually not high level, consisting mostly of case series and case reports. Only a rare randomized controlled trial has been accomplished. Radiation injury is one of the UHMS "approved" indications, and third-party payors will usually reimburse for this application. This updated review summarizes the publications available reporting results in treating radiation-injured patients. Mechanisms of HBO2 in radiation injury are discussed briefly. Outcome is reported on a mostly anatomic basis though due to the nature of the injury a positive outcome at one anatomic site is supportive of HBO2 at other sites. The potential benefit of prophylactic HBO2 before frank damage is also discussed in high-risk patients. The concerns of HBO2 enhancing growth of or precipitating recurrence of malignancy is discussed and largely refuted.

Prospective assessment of outcomes in 411 patients treated with hyperbaric oxygen for chronic radiation tissue injury.

BACKGROUND: Although hyperbaric oxygen is used to treat chronic radiation tissue injury, clinical evidence supporting its efficacy has been limited to date. The authors report prospectively collected patient outcomes from a single center's large experience using hyperbaric oxygen to treat chronic radiation injury. METHODS: Since 2002, patient outcomes at the conclusion of a course of hyperbaric oxygen treatment for chronic radiation tissue injury at Virginia Mason Medical Center in Seattle have been graded by a board-certified hyperbaric physician and prospectively recorded. From 2002 to 2010, a total of 525 patients received treatment for 1 of 6 forms of radionecrosis analyzed. After excluding 114 patients for incomplete records or treatment courses or for previous receipt of hyperbaric oxygen therapy, records of 411 patients were retrospectively reviewed in 2010, and outcomes were regraded by a second board-certified physician. A positive clinical response was defined as an outcome graded as either "resolved" (90%-100% improved) or "significantly improved" (50%-89% improved). RESULTS: A positive outcome from hyperbaric treatment occurred in 94% of patients with osteoradionecrosis of the jaw (n = 43), 76% of patients with cutaneous radionecrosis that caused open wounds (n = 58), 82% of patients with laryngeal radionecrosis (n = 27), 89% of patients with radiation cystitis (n = 44), 63% of patients with gastrointestinal radionecrosis (n = 73), and 100% of patients who were treated in conjunction with oral surgery in a previously irradiated jaw (n = 166). CONCLUSIONS: The outcomes of 411 patients collected prospectively over 8 years strongly supported the efficacy of hyperbaric oxygen treatment for the 6 conditions evaluated. The response rates previously reported in numerous small series were supported by the responses achieved in this large, single-center experience.

Prophylactic hyperbaric oxygen treatment and rat spinal cord re-irradiation.

Normal tissue injury may lead to severe, life threatening, late side effects after therapeutic use of irradiation. Neurological complications caused by radiation of the spinal cord are ascribed to progressive, irreversible damage to the vasculature. Hyperbaric oxygen (HBO) is known to induce angiogenesis in irradiated tissue and has been proven to reduce late radiation injury in several normal tissues when applied during the latent period before complications become manifest. In the present study: (1). the prophylactic potential of HBO; (2). optimal timing of HBO therapy after spinal cord irradiation, i.e. during the latent period; and (3). effect of HBO on the re-irradiation tolerance of the spinal cord were investigated. The rat cervical spinal cord was locally X-ray irradiated with ten fractions of 6.5 Gy in 11 days. Five treatment groups (n=10) included: irradiation alone and irradiation followed by 30 HBO treatments (100% oxygen at 240 kPa for 90 min) during latency, with HBO starting either immediately, 5, 10 or 15 weeks after the primary irradiation course. One year after the primary treatment, the same spinal cord volume was re-irradiated with 20 Gy single dose. During life span, the animals were observed on the incidence of myelitis and the duration of the latent period. The actuarial analysis revealed no significant difference in neurological complications free survival between the irradiation alone and the irradiation+HBO treatment groups. A tendency towards radiosensitization was found in the group in which the primary irradiation course was immediately followed by the HBO treatment course. The data show that HBO applied during the latent period of progressively developing irradiation damage to the spinal cord does not increase the re-irradiation tolerance of this tissue.