The effect of hyperbaric oxygen therapy in head and neck cancer patients with radiation induced dysphagia-a systematic review.

PURPOSE: The aim of this systematic review was to assess the role of hyperbaric oxygen therapy  (HBOT) in patients with dysphagia after radiation therapy for head and neck cancer. METHOD: A systematic search was conducted in the electronic databases Ovid MEDLINE, Ovid Embase, and Cochrane Central Register of Controlled Trials for relevant studies until March 14, 2023. No restriction on language or publication date. The criteria for inclusion: patients with HNC who had received both radiation therapy and HBOT as 1) a preventive treatment against swallowing difficulties, 2) to preserve swallowing function, or 3) to promote swallowing difficulties. RESULTS: We identified 1396 records. After removal of 31 duplicates, 1365 records were accessible for title and abstract screening. This yielded 53 studies for full text assessment. Six studies met the eligibility criteria and were included for qualitative analysis. CONCLUSION: Evidence of HBOT benefits in patients with dysphagia after radiation therapy for head and neck cancer is inconsistent. Well-designed studies using validated outcome measures and long-term follow-up are warranted.

Prevention and Management of Osteoradionecrosis in Patients With Head and Neck Cancer Treated With Radiation Therapy: ISOO-MASCC-ASCO Guideline.

PURPOSE: To provide evidence-based recommendations for prevention and management of osteoradionecrosis (ORN) of the jaw secondary to head and neck radiation therapy in patients with cancer. METHODS: The International Society of Oral Oncology-Multinational Association for Supportive Care in Cancer (ISOO-MASCC) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library databases were searched for randomized controlled trials and observational studies, published between January 1, 2009, and December 1, 2023. The guideline also incorporated systematic reviews conducted by ISOO-MASCC, which included studies published from January 1, 1990, through December 31, 2008. RESULTS: A total of 1,539 publications were initially identified. There were 487 duplicate publications, resulting in 1,052 studies screened by abstract, 104 screened by full text, and 80 included for systematic review evaluation. RECOMMENDATIONS: Due to limitations of available evidence, the guideline relied on informal consensus for some recommendations. Recommendations that were deemed evidence-based with strong evidence by the Expert Panel were those pertaining to best practices in prevention of ORN and surgical management. No recommendation was possible for the utilization of leukocyte- and platelet-rich fibrin or photobiomodulation for prevention of ORN. The use of hyperbaric oxygen in prevention and management of ORN remains largely unjustified, with limited evidence to support its practice.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1.

PURPOSE: Osteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials. METHODS AND MATERIALS: Patients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups. RESULTS: In group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients. CONCLUSION: Hyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error.

Mesenchymal Stem Cell Therapy for Osteoradionecrosis of the Mandible: a Systematic Review of Preclinical and Human Studies.

BACKGROUND: Osteoradionecrosis (ORN) of the mandible is a severe complication of radiotherapy for head and neck cancer and is arduously difficult to manage. Current treatment options carry risks with some patients remaining incurable. Mesenchymal stromal/stem cell (MSC) therapy has shown promising results supporting osteogenesis and regeneration of radiotherapy-damaged tissues. The aim of this study was to systematically review the literature on the safety and efficacy of MSCs in treating ORN. METHODS: A systematic search was performed on MEDLINE, Embase, Cochranes Library online databases, and clinicaltrials.gov to identify preclinical and clinical studies examining the effect of MSCs on osseous healing of ORN. The preclinical studies were assessed according to the SYRCLEs guidelines and risk of bias tool. RESULTS: Six studies (n = 142) from 5 countries were eligible for analysis. Of these four were preclinical studies and two clinical case studies. Preclinical studies found MSC treatment to be safe, demonstrating bone restorative effects and improved soft tissue regeneration. In the clinical cases, healing of bone and soft tissue was reported with no serious adverse events. CONCLUSION: The evidence from the included studies suggests that MSCs may have beneficial regenerative effects on the healing of ORN. None of the studies reported adverse events with the use of MSCs. More carefully controlled studies with well-identified cells are however needed to demonstrate the efficacy of MSCs in a clinical setting. Graphical abstract.

Only minor stem cell mobilization in head and neck irradiated patients treated with hyperbaric oxygen.

INTRODUCTION: Hyperbaric oxygen, (HBO) is used to treat several conditions including late radiation tissue injury. Previous studies have suggested that HBO mobilizes bone marrow derived stem/progenitor cells (SPC) to the peripheral blood, however possible cumulative effects were highly variable. METHODS: We have investigated a possible HBO-induced mobilization of SPCs by determining CD34+CD45dim cell numbers, as well as SPCs in general. The latter were characterized by high aldehyde dehydrogenase (ALDH) activity by use of the Aldefluor® assay. We included ten patients admitted for HBO treatment of radiation tissue injury. Six patients completed the 29-30 HBO treatment exposures. We also investigated possible HBO-induced effects on platelet activation as measured by flow cytometry and functional analyses. RESULTS: We found a weak and insignificant tendency toward mobilization of CD34+CD45dim cells after a single HBO exposure versus before. Additionally, we found an additive effect of 15 HBO exposures on the increase in CD34+CD45dim cells relative to the pre-1st-HBO values. These changes were significantly more than zero but less than a doubling. We could not demonstrate a significant effect of HBO on the content of Aldefluor® positive SPCs in peripheral blood. There was no significant effect on platelet activation overall. However, in patients with increased expression of activation markers at baseline, we found a decrease after one exposure although this was not reflected in functional tests. CONCLUSION: We found a minor statistically significant mobilizing effect of HBO treatment on the bone marrow derived stem/progenitor cell content in peripheral blood after 15 treatments (n = 10 patients), but no effect after 30 treatments (n = 6 patients). However, because of the low number of patients we cannot confidentially prove or disprove the null hypothesis. The possibility that HBO treatment reduces the number of activated platelets could not be demonstrated nor excluded.

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.

Survey of referral patterns and attitudes toward hyperbaric oxygen treatment among Danish oncologists, ear, nose and throat surgeons and oral and maxillofacial surgeons.

In head and neck cancer patients with late radiation injury, hyperbaric oxygen (HBO) is used for therapeutic or prophylactic reasons against soft-tissue and osteoradionecrosis (ORN). Twenty-nine departments of oncology, ENT, oral and maxillofacial (OMF) surgery were surveyed using the Enalyzer tool (www.enalyzer.com), of whom 21 responded. Data were incomplete in four returns. Within the previous year, 14 departments had referred at least one patient for hyperbaric oxygen therapy (HBOT). There appears to be a generally positive attitude in Danish OMF, ENT and oncology departments towards referral of patients with ORN for HBOT. However, there is an increasing desire for better evidence for its role in head and neck cancer in the prevention and treatment of soft-tissue injury and osteonecrosis following radiotherapy.

Patient's perspective on hyperbaric oxygen treatment of osteoradionecrosis.

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.

Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study.

Irradiated head and neck cancer survivors treated in the Hyperbaric Oxygen (HBO) Unit, Copenhagen University Hospital, spontaneously reported improvement of radiation-induced dry mouth feeling. The aim of this pilot study was to evaluate salivary flow rate and xerostomia before and after HBO in irradiated head and neck cancer patients. Eighty patients eligible for HBO treatment on the indication of prevention/treatment of osteoradionecrosis or soft tissue radiation injury were consecutively sampled, of whom 45 had hyposalivation (i.e. unstimulated whole saliva (UWS) flow rate <0.1ml/min), and 69 complained of xerostomia. UWS and stimulated whole saliva (SWS) were collected prior to and after 30 sessions of hyperbaric oxygen treatment over 6weeks. Xerostomia was assessed using the visual analogue scale (VAS). Each HBO session involved compression to 243kPa (2.4 ATA) for 90min while breathing 100% oxygen from a facemask or hood. There was a significant decrease in xerostomia (p<0.001) and slight increase in UWS (p<0.001) and SWS (p<0.001) flow rate, from before HBO as compared to after. Twenty-five of 45 patients with hyposalivation achieved an increased UWS flow rate after HBO. In 12 of these, the flow rates increased to levels not associated with hyposalivation. Patient-assessed improvement of xerostomia and slightly increased UWS and SWS secretion after HBO treatment suggest that HBO may have a beneficial effect on radiation-induced salivary gland damage.

Increased plasma levels of IL-6 in bacteremic periodontis patients after scaling.

Bacteremia frequently occurs after dental treatment. Periodontal inflammation may influence the incidence, magnitude and duration of bacteremia. The presence of circulating oral bacteria or bacterial components may induce cytokine synthesis in blood cells, which may contribute to the development or exacerbation of atherosclerosis. The present study tested the hypothesis that bacteremia occurring after scaling in periodontitis patients results in altered plasma levels of cytokines. Twenty periodontitis patients were subjected to scaling. Blood samples at baseline and at 0.5, 10 and 30 minutes postscaling were examined for bacteremia whereas baseline and eight-hour postscaling blood samples were examined for the levels of IL-1beta, TNF-alpha, IL-6, IL-8, IL-10 and IL-12p70. IL-6 levels were significantly increased eight hours after scaling, while IL-8 was significantly decreased. No systematic changes occurred in the levels of IL-1beta, TNF-alpha, IL-10 and IL-2p70. IL-6 levels may be increased while IL-8 may be decreased due to scaling, which may have implications for general health.

Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation.

UNLABELLED: SCIENTIFIC RATIONALE FOR STUDY: Bacteremia occurs with various frequency after oral procedures. Periodontal disease may affect the incidence, magnitude, duration and bacterial spectrum of bacteremia. PRINCIPLE FINDINGS: The incidence and magnitude of bacteremia after scaling was significantly higher in periodontitis than in gingivitis patients and healthy control individuals. In periodontitis patients, the magnitude of bacteremia was associated with gingival index, plaque index and number of sites with bleeding on probing, but not with probing pocket depth measurements. PRACTICAL IMPLICATIONS: The prevention and treatment of periodontal diseases appear to be crucial for the prevention of bacteremia associated with oral procedures.