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.

The role of hyperbaric oxygen in osteoradionecrosis-a prophylactic insight.

BACKGROUND: Osteoradionecrosis (ORN) is an uncommon and debilitating consequence of head and neck radiotherapy and hyperbaric oxygen therapy (HBOT) has been advocated for prophylaxis prior to performing dentoalveolar procedures. The aim of this study was to evaluate a prophylactic HBOT protocol and describe the outcomes of susceptible individuals. METHODS: A retrospective audit of adults who attended the Oral and Maxillofacial Surgery department at the Royal Adelaide Hospital (South Australia) who received dental extractions with a history of radiotherapy to the jaws from 2008 to 2020. Data including demographic information and outcomes of osteoradionecrosis and delayed healing was recorded. RESULTS: A total of 121 individuals were eligible for case note review; 68.6% of individuals were male and 55.4% were aged over 67 years. Osteoradionecrosis occurred in 9.1% of individuals and delayed healing for 3.3%; fifteen individuals (12.4%) were unable to complete the HBOT protocol. The individuals who were diagnosed with ORN had a significant association with age (P = 0.006) and binary analysis showed alcohol consumption to be a significant predictor. CONCLUSIONS: Prophylactic HBOT protocol had a lower proportion of individuals diagnosed with ORN and those who were diagnosed were more likely to be younger males and have current alcohol consumption.

Overview and Emerging Trends in the Treatment of Osteoradionecrosis.

OPINION STATEMENT: Osteoradionecrosis (ORN) of the mandible is a rare but devastating complication which occurs following radiation therapy for head and neck malignancies. Left untreated, ORN often results in pathologic fracture of the mandible leading to pain, trismus, difficulty eating, and overall poor quality of life. Historically, early intervention relied on hyperbaric oxygen and local debridement. Patients whose disease progressed despite therapy required segmental resection of the mandible with osseous free flap reconstruction, a highly invasive operation. Patients that presented with a moderate disease without pathologic fracture were often doomed to fail non-operative management, ultimately leading to disease progression and fracture. The traditional dichotomous treatment paradigm left a void of options for patients with moderate disease. The ideal intervention for this category of patients would provide renewed vascularity to the diseased tissue bed allowing for the osteogenesis and reestablishment of strong, load-bearing bone. The innovative technique termed the vascularized fascia lata "rescue flap" has proven to be an effective treatment for moderate ORN and will likely transform dated treatment algorithms.

Interventions for preventing osteoradionecrosis of the jaws in adults receiving head and neck radiotherapy.

BACKGROUND: Osteoradionecrosis (ORN) of the jaws is among the most serious oral complications of head and neck cancer radiotherapy, arising from radiation-induced fibro-atrophic tissue injury, manifested by necrosis of osseous tissues and failure to heal, often secondary to operative interventions in the oral cavity. It is associated with considerable morbidity and has important quality of life ramifications. Since ORN is very difficult to treat effectively, preventive measures to limit the onset of this disease are needed; however, the effects of various preventive interventions has not been adequately quantified. OBJECTIVES: To assess the effects of interventions for preventing ORN of the jaws in adult patients with head and neck cancer undergoing curative or adjuvant (i.e. non-palliative) radiotherapy. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 5 November 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 10) in the Cochrane Library (searched 5 November 2019), MEDLINE Ovid (1946 to 5 November 2019), Embase Ovid (1980 to 5 November 2019), Allied and Complementary Medicine (AMED) Ovid (1985 to 5 November 2019), Scopus (1966 to 5 November 2019), Proquest Dissertations and Theses International (1861 to 5 November 2019) and Web of Science Conference Proceedings (1990 to 5 November 2019). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) or quasi-RCTs of adult patients 18 years or older with head and neck cancer who had undergone curative or adjuvant radiotherapy to the head and neck, who had received an intervention to prevent the onset of ORN. Eligible patients were those subjected to pre- or post-irradiation dental evaluation. Management of these patients was to be with interventions independent of their cancer therapy, including but not limited to local, systemic, or behavioural interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials from search results, assessed risk of bias, and extracted relevant data for inclusion in the review. Authors of included studies were contacted to request missing data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Four studies were identified that met pre-determined eligibility criteria, evaluating a total of 342 adults. From the four studies, all assessed as at high risk of bias, three broad interventions were identified that may potentially reduce the risk of ORN development: one study showed no reduction in ORN when using platelet-rich plasma placed in the extraction sockets of prophylactically removed healthy mandibular molar teeth prior to radiotherapy (odds ratio (OR) 3.32, 95% confidence interval (CI) 0.58 to 19.09; one trial, 44 participants; very low-certainty evidence). Another study involved comparing fluoride gel and high-content fluoride toothpaste (1350 parts per million (ppm)) in prevention of post-radiation caries, and found no difference between their use as no cases of ORN were reported (one trial, 220 participants; very low-certainty evidence). The other two studies involved the use of perioperative hyperbaric oxygen (HBO) therapy and antibiotics. One study showed that treatment with HBO caused a reduction in the development of ORN in comparison to patients treated with antibiotics following dental extractions (risk ratio (RR) 0.18, 95% CI 0.43 to 0.76; one trial, 74 participants; very low-certainty evidence). Another study found no difference between combined HBO and antibiotics compared to antibiotics alone prior to dental implant placement (RR 3.00, 95% CI 0.14 to 65.16; one trial, 26 participants; very low-certainty evidence). Adverse effects of the different interventions were not reported clearly or were not important. AUTHORS' CONCLUSIONS: Given the suboptimal reporting and inadequate sample sizes of the included studies, evidence regarding the interventions evaluated by the trials included in this review is uncertain. More well-designed RCTs with larger samples are required to make conclusive statements regarding the efficacy of these interventions.

Challenges threaten, opportunity awaits hyperbaric medicine and the head and neck cancer patient.

Over the past four decades, hyperbaric oxygen (HBO2) therapy has played a prominent role in both the prevention and treatment of mandibular osteoradionecrosis (ORN). It has done so on the strength of laboratory observations and clinical reports, yet only limited efficacy data. This dual role has come under increasing scrutiny in the modern radiotherapy (RT) and surgical eras. The ability to spare healthy "non-target" tissue has markedly improved since the two-dimensional planning and delivery techniques in use when HBO2's prophylactic value was first demonstrated. A recent study failed to identify this same benefit in patients who received high-precision imaging and conformal RT. HBO2 therapy is under challenge as preferred treatment for early stage ORN. A recently introduced "fibroatrophic" mechanism contrasts with the hypovascular-hypocellular-hypoxic injury pattern that formed the basis for HBO2's therapeutic use. This alternative pathophysiologic state appears to benefit from an oral antioxidant medication regimen. The continuing necessity of HBO2 in support of mandibular reconstruction for advanced ORN is in question. Microsurgery-based vascularized bone flaps increasingly represent standard care, invariably in the absence of perioperative HBO2. Renewed interest in hyperbaric oxygen as a radiation sensitizer offers some promise. Hypoxia remains a critical radio-resistant factor in many solid tumors. Malignant gliomas have been a primary focus of several small studies, with resulting improvements in local control and median survival. Hyperbaric radiation sensitization has recently addressed oropharyngeal cancer. Preliminary data indicates that addition of HBO2 to chemo-radiation standard of care is technically feasible, well tolerated and safe. A Phase II efficacy trial will investigate the potential for of HBO2 to improve progression-free and relapse-free survival in newly diagnosed locally advanced head and neck cancers. What follows is a review and summary of relevant peer-reviewed literature.

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery.

PURPOSE: Hyperbaric oxygen (HBO) has been advocated in the prevention and treatment of osteoradionecrosis (ORN) of the jaw after head and neck radiation therapy, but supporting evidence is weak. The aim of this randomized trial was to establish the benefit of HBO in the prevention of ORN after high-risk surgical procedures to the irradiated mandible. METHODS AND MATERIALS: HOPON was a randomized, controlled, phase 3 trial. Participants who required dental extractions or implant placement in the mandible with prior radiation therapy >50 Gy were recruited. Eligible patients were randomly assigned 1:1 to receive or not receive HBO. All patients received chlorhexidine mouthwash and antibiotics. For patients in the HBO arm, oxygen was administered in 30 daily dives at 100% oxygen to a pressure of 2.4 atmospheres absolute for 80 to 90 minutes. The primary outcome measure was the diagnosis of ORN 6 months after surgery, as determined by a blinded central review of clinical photographs and radiographs. The secondary endpoints included grade of ORN, ORN at other time points, acute symptoms, pain, and quality of life. RESULTS: A total of 144 patients were randomized, and data from 100 patients were analyzed for the primary endpoint. The incidence of ORN at 6 months was 6.4% and 5.7% for the HBO and control groups, respectively (odds ratio, 1.13; 95% confidence interval, 0.14-8.92; P = 1). Patients in the hyperbaric arm had fewer acute symptoms but no significant differences in late pain or quality of life. Dropout was higher in the HBO arm, but the baseline characteristics of the groups that completed the trial were comparable between the 2 arms. CONCLUSIONS: The low incidence of ORN makes recommending HBO for dental extractions or implant placement in the irradiated mandible unnecessary. These findings are in contrast with a recently published Cochrane review and previous trials reporting rates of ORN (non-HBO) of 14% to 30% and challenge a long-established standard of care.

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): a randomised controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible: study protocol for a randomised controlled trial.

BACKGROUND: Osteoradionecrosis of the mandible is the most common serious complication of radiotherapy for head and neck malignancy. For decades, hyperbaric oxygen has been employed in efforts to prevent those cases of osteoradionecrosis that are precipitated by dental extractions or implant placement. The evidence for using hyperbaric oxygen remains poor and current clinical practice varies greatly. We describe a protocol for a clinical trial to assess the benefit of hyperbaric oxygen in the prevention of osteoradionecrosis during surgery on the irradiated mandible. METHODS/DESIGN: The HOPON trial is a phase III, randomised controlled, multi-centre trial. It employs an unblinded trial design, but the assessment of the primary endpoint, i.e. the diagnosis of osteoradionecrosis, is assessed on anonymised clinical photographs and radiographs by a blinded expert panel. Eligibility is through the need for a high-risk dental procedure in the mandible where at least 50-Gy radiotherapy has been received. Patients are randomised 1:1 to hyperbaric oxygen arm (Marx protocol) : control arm, but both groups receive antibiotics and chlorhexidine mouthwash. The primary endpoint is the presence of osteoradionecrosis at 6 months following surgery, but secondary endpoints include other time points, acute symptoms and pain, quality of life, and where implants are placed, their successful retention. DISCUSSION: The protocol presented has evolved through feasibility stages and through analysis of interim data. The classification of osteoradionecrosis has undergone technical refinement to ensure that robust definitions are employed. The HOPON trial is the only multi-centre RCT conducted in this clinical setting despite decades of use of hyperbaric oxygen for the prevention of osteoradionecrosis. TRIAL REGISTRATION: European Clinical Trials Database, ID: EudraCT200700622527 . First registered on 5 November 2007.

The Use of Hyperbaric Oxygen for the Prevention and Management of Osteoradionecrosis of the Jaw: A Dana-Farber/Brigham and Women's Cancer Center Multidisciplinary Guideline.

BACKGROUND: Osteoradionecrosis of the jaw (ORN) is an infrequent yet potentially devastating complication of radiation therapy to the head and neck region. Treatment options include antimicrobial therapy, local sequestrectomy, resection, and the use of hyperbaric oxygen (HBO). Published data on ORN are difficult to compare because of the lack of a universally accepted classification and staging system, and the literature on the use of HBO to either prevent or successfully manage ORN is controversial and inconclusive. Therefore, we aimed to establish a standard approach for using HBO at our institution. MATERIALS AND METHODS: A literature search was conducted of articles published in the English language between January 1980 and January 2016. Retrieved articles were evaluated by two independent reviewers. Isolated case reports, abstracts, case series, review articles, and cohort studies without a control group were excluded; summary data were extracted from the remaining studies. A panel of experts from Head and Neck Oncology and Oral Medicine from the Dana-Farber Cancer Institute and Brigham and Women's Hospital reviewed the summary data and established multidisciplinary guidelines on the use of HBO for the prevention and management of ORN. RESULTS: Seven studies were evaluated and reviewed by the multidisciplinary panel. There was no consistent evidence in support of HBO for either the prevention or management of ORN. CONCLUSION: Based on the available evidence and expert opinion, routine use of HBO for the prevention or management of ORN is not recommended and is rarely used at our institution. The Oncologist 2017;22:343-350 IMPLICATIONS FOR PRACTICE: The Division of Head and Neck Oncology of Dana-Farber/Brigham and Women's Cancer Center does not recommend the routine use of HBO for the prevention or management of ORN. Adjunctive HBO may be considered for use on a case-by-case basis in patients considered to be at exceptionally high risk who have failed conservative therapy and subsequent surgical resection.

Current Concepts in Osteoradionecrosis after Head and Neck Radiotherapy.

Osteoradionecrosis (ORN) of the jaws is a feared complication of head and neck radiotherapy. ORN causes significant morbidity for patients and controversy among clinicians. This overview considers the variations in definition and classification of the condition that affect estimates of incidence and also the interpretation of evidence. The influence of newer radiotherapy techniques in reducing ORN through reduced dose and xerostomia is balanced against a probable increase in a vulnerable population through a rising head and neck cancer incidence. Theories of pathophysiology of ORN include radiation-induced osteomyelitis, hypoxic and hypovascular theory and fibroatrophic theory. Prevention strategies include restorative dentistry and radiation planning techniques. Treatments range from conservative 'watch and wait' through to more radical surgical strategies. Newer medical management strategies are available with a limited evidence base. The use of hyperbaric oxygen therapy remains controversial and the background and need for newer hyperbaric oxygen trials is discussed.

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.

Comparison of Australian and New Zealand referral rates for hyperbaric oxygen in oro-facial osteoradionecrosis: evidence-based, funding constraint or clinician whim?

AIM: To compare Australian and New Zealand (NZ) rates of referral to hyperbaric units for patients with, or at risk of developing mandibular or maxillary osteoradionecrosis (ORN) due to a history of radiotherapy for oro-pharyngeal cancer. METHOD: Relevant patient treatment data from all hyperbaric units in Australia and NZ were collated and analysed. RESULTS: The rate of referral to hyperbaric units in Australia for treatment or prophylaxis of patients with, or at risk of oro-facial ORN, was 1.7 times the rate of referral in NZ. Within Australia, there was a greater than three-fold interstate variation. CONCLUSION: There is a significant referral rate difference both within Australia and between Australia and NZ for hyperbaric oxygen therapy for oro-facial ORN. Possible reasons for this difference include access to funding, logistical difficulties, clinician preference for an alternative treatment and clinician attitudes to hyperbaric oxygen.

Hyperbaric oxygen therapy as a prevention modality for radiation damage in the mandibles of mice.

BACKGROUND: Radiation therapy (RT) as part head and neck cancer treatment often leads to irradiation of surrounding normal tissue, such as mandibular bone. A reduced reparative capacity of the bone can lead to osteoradionecrosis (ORN). Hyperbaric oxygen therapy (HBOT) is used to treat ORN, based on its potential to raise the oxygen tension in tissues. However, prevention of radiation-induced damage is of great interest. Our purpose was to investigate whether HBOT could prevent radiation-induced damage to murine mandibles. METHODS: Twenty-eight mice were irradiated in the head and neck region with a single dose (15 Gy) and half of them were subsequently subjected to HBOT. Another 14 mice did not receive any treatment and served as controls. Ten and 24 weeks after RT, mandibles were harvested and analysed histologically and by microcomputed tomography (micro-CT). RESULTS: Micro-CT analysis showed a reduction in relative bone volume by RT, which was partly recovered by HBOT. Trabecular thickness and separation were also positively influenced by HBOT. Morphologically, HBOT suppressed the osteoclast number, indicating decreased resorption, and decreased the amount of lacunae devoid of osteocytes, indicating increased bone viability. CONCLUSIONS: HBOT was able to partly reduce radiation-induced effects on microarchitectural parameters, resorption, and bone viability in mouse mandibles. HBOT could therefore potentially play a role in the prevention of radiation-induced damage to human mandibular bone.

The use of ozone in the prevention of osteoradionecrosis of the jaw.

Radiation therapy of the head and neck area has resulted in numerous and undesired effects on the oral cavity tissue. The most frequent and most dangerous complications of radiotherapy of the head and neck area is osteoradionecrosis (ORN). The purpose of this study is to demonstrate the possibility of using ozone in the prevention of ORN of the jaw, and show the recent therapeutic protocols for treatment in patients receiving radiation therapy for the head and neck. We used an ElektroMagneTron device during the therapy. The patient underwent postoperative follow-up examination when bio-oxygenation therapy and clinical evaluation of wound healing were performed. Wound healing evaluation showed no complications. Ozone therapy is given as an option in the therapeutic protocol for the prevention and treatment of ORN. 

Dental management of patients irradiated for head and neck cancer.

Patients undergoing radiation therapy as either primary, adjuvant, combination therapy or palliative management of head and neck malignancies are prone to a range of dental complications. Strategies for prevention and management of such complications may be controversial. This article aims to highlight the current understanding and management of the dental needs for patients before, during and after radiation therapy.

Hyperbaric oxygen and dental extractions in irradiated patients: short- and long-term outcomes.

PURPOSE: Mandibular osteoradionecrosis (ORN) can occur in patients post-radiation therapy. This study assessed the incidence of ORN in the setting of adjunctive hyperbaric oxygen therapy (HBO2) and sought to identify risk factors that may predispose to its development. METHODS: A retrospective chart review was completed on patients with a history of radiation therapy to the head and neck who underwent HBO2 prior to and immediately following dental extractions between January 1, 1995, and December 31, 2005, in the hyperbaric medicine unit. RESULTS: The incidence of ORN in 40 patients immediately following completion of HBO was 0%. Available follow-up longer than six months after completion of HBO2 on 19 of these patients showed an incidence of ORN increased to 15.8%. None of the considered risk factors for development of ORN reach statistical significance. CONCLUSION: The incidence of ORN at the completion of HBO2 was less than previously reported incidences between 1.5%-4.2%. However, long-term follow-up indicated a much higher incidence of 15.8%. The difference in incidence of ORN immediately upon completion of HBO2 approximately two weeks after dental extractions compared to that at least six months later identifies a need for more long-term follow-up of these patients following their dental extractions.

Professional attitudes in regard to hyperbaric oxygen therapy for dental extractions in irradiated patients: a comparison of two specialties.

OBJECTIVES: Mandibular osteoradionecrosis (ORN) is a serious complication of radiation therapy. The current use of hyperbaric oxygen therapy (HBO2) to prevent ORN when dental extractions are performed has been called into question. We sought to determine the current acceptability and confidence in this treatment by practitioners from two different specialties. METHODS: We surveyed both hyperbaric medicine physicians and radiation oncologists regarding their views on the use of HBO2 for the prevention of ORN. Separate web-based anonymous surveys were sent via email invitation. These two groups were compared, including statistical analysis using the chi-square test when appropriate. RESULTS: 175 radiation oncologists and 118 hyperbaric medicine physicians participated. Among those not recommending HBO2, lack of evidence was cited by 52% of radiation oncologists and 38% of hyperbaric medicine physicians (chi2 = 5.0, p = 0.03, 95%, CI 1.9% to 25.6%). A majority of radiation oncologists (79%) and hyperbaric medicine physicians (85%) believe it is important that a new randomized controlled trial (RCT) is conducted (chi2 = 1.3, p = NS). CONCLUSIONS: While HBO2 has been used for decades, recent tissue-sparing radiation techniques and advanced surgical techniques are now calling into question the continued use of HBO2 for ORN prevention. Our results demonstrate that there is overwhelming support among responding practitioners for a new RCT.

Assessment of the effect of low-energy diode laser irradiation on gamma irradiated rats' mandibles.

OBJECTIVE: The purpose of the present study was to evaluate the biostimulative and regenerative effects of low intensity laser irradiation (LILT) (applied before or after initiation of radiotherapy) on gamma irradiated rats' jaw bones. METHODS: Forty eight male Albino rats were equally divided into two groups: group 1, in which the left side of the mandible was subjected to three successive sessions of laser (LILT) prior to whole body gamma radiation (2Gy/3 fractions/week) and group 2, received whole body gamma radiation (2Gy/3 fractions/week) prior to three successive sessions of laser applied to left side. The right side of both groups was used as gamma irradiated non-lased control group. Each group was then subdivided into four equal subgroups (a, b, c, d) according to the time of scarification (3, 7, 14, 21 days respectively). Specimens were subjected to histological, histomorphometric and scanning electron microscopic examinations. RESULTS: Thin irregular bone trabeculae and widened marrow spaces were identified in the control group. The lased sides of groups 1 and 2 demonstrated regular, thick and continuous bone trabeculae. Ultrastructurally, collagen fibres of the control group appeared irregularly arranged and more spaced compared to groups 1 and 2. Normal-sized osteocytic lacunae were seen in the lased groups, as compared to the wide lacunar spaces noted in the control group. Histomorphometric analysis showed a significant increase in the area of bone trabeculae, as well as the width of compact bone, for the lased groups. CONCLUSIONS: LILT seemed to attenuate the radiation-related damage in alveolar bones.

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.