Rehabilitation of oral function in head and neck cancer patients after radiotherapy with implant-retained dentures: effects of hyperbaric oxygen therapy. Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. Radiation therapy with hyperbaric oxygen at 4 atmospheres pressure in the management of squamous cell carcinoma of the head and neck: results of a randomized clinical trial. Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain. Carcinoma of the cervix: results of a hyperbaric oxygen trial associated with the use of the cathetron. Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy. Hyperbaric oxygen and thrombolysis in myocardial infarction: the 'HOT MI' randomized multicenter study. Early hyperbaric oxygen therapy for reducing radiotherapy side effects: early results of a randomized trial in oropharyngeal and nasopharyngeal cancer. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer.
Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy often result in an anatomic and physiological oral condition unfavorable for prosthodontic rehabilitation. The objective of this prospective study was to assess the effect of hyperbaric oxygen therapy on treatment outcome (condition of peri-implant tissues, implant survival, oral functioning and quality of life) of prosthodontic rehabilitation with implant-retained lower dentures in radiated head and neck cancer patients 6 weeks and 1 year after placing the new dentures. The treatment outcome was assessed in a group of 26 head neck cancer patients who were subjected to radiotherapy after tumour surgery. Standardized questionnaires were completed and clinical and radiographic assessments were performed. After randomization, endosseous Brånemark implants were placed in the anterior part of the mandible either under antibiotic prophylaxis (13 patients) or under antibiotic prophylaxis combined with pre and postsurgery hyperbaric oxygen (HBO) treatment (13 patients). In the HBO and non-HBO group eight implants (implant survival 85.2%) and three implants (implant survival 93.9%) were lost, respectively. Peri-implant tissues had a healthy appearance in both groups. Osteoradionecrosis developed in one patient in the HBO group. All patients functioned well with their implant-retained lower denture. The quality of life related to oral functioning and denture satisfaction were improved to a comparable extent in the HBO and non-HBO group. Implant-retained lower dentures can improve the quality of life related to oral functioning and denture satisfaction in head and neck cancer patients. Adjuvant hyperbaric oxygen therapy could not be shown to enhance implant survival in radiated mandibular jaw bone. To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis.
                This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety.
                At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms.
                Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation. The purpose of this study was to present the results of a randomized trial evaluating HBO-4 in combination with hypofractionated radiation therapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
                Between April 1974 and December 1975, 48 patients with locally advanced unresected SCCHN, referred for primary radiation therapy, were randomized to radiation delivered in air in two fractions of 12.65 Gy over 21 days to a total of 25.30 Gy (air, n = 25); or radiation under HBO-4 in two fractions of 11.50 Gy over 21 days to at total of 23.00 Gy (HBO-4, n = 23). The HBO-4 was administered under general anesthesia to minimize patient discomfort and potential problems with seizures associated with rapid compression to 4 atmospheres. Patients were monitored regularly by the radiation oncologists for toxicity, response, local control, and survival. The original hospital records, radiation records, and hyperbaric treatment logs were recently reviewed, and all data were entered onto a computerized database for the current analysis. The results of this trial have not previously been published.
                The air and HBO-4 arms were evenly matched with respect to age, sex, performance status, hemoglobin level, primary site, and stage of disease. Acute toxicities were acceptable with no significant differences between the two treatment arms. A trend toward excess severe late complications were noted in the hyperbaric arm (12 vs 7). There was a highly significant difference in complete clinical responses between the two arms, with 21/25 in complete dinical responses in the HBO-4 arm compared with 13/25 in complete clinical responses in the air arm, and a statistically insignificant trend toward improved 5-year local control in the HBO-4 arm (29% vs 16%). There were no significant differences between the two arms with respect to 5-year survival, distant metastasis, or second primary tumors.
                Long-term outcome from this historical randomized trial demonstrate substantial improvements in response rate with the use of HBO-4. The hypofractionation scheme used in the trial resulted in relatively low local control and high complication rates in this group of patients with very advanced SCCHN. However, these results support the theory that radioresistant hypoxic cells limit the radiocurability of SCCHN. Further investigations addressing the hypoxic cell problem with hypoxic cytotoxins or hypoxic cell sensitizers in combination with radiation therapy using more conventional fractionation schemes are warranted. Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain.
                Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neuropsychological test at 3 months without treatment in that period and started HBO thereafter.
                All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance.
                HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement. Since 1971, 82 patients with advanced carcinoma of the cervix have been included in a randomised clinical trial in association with the Working Party on Radiotherapy and Hyperbaric Oxygen of the Medical Research Council. External irradiation was given in 10 fractions by an unconventional schedule, either in air or HBO, and combined with three large fractions of intracavitary irradiation using the Cathetron. The results are acceptable overall, with 69% local control, 15% with tumour developing outside the treated volume and 40% survival at five years, but no improvement has been shown with HBO. Symptoms suggestive of some degree of late damage to the small bowel were present in 13% of patients, with a higher but not statistically significant, incidence in the HBO group. It is postulated that the schedule of radiotherapy used has allowed reoxygenation during treatment and that no further gain due to the use of HBO may be achieved. After a review of the results from other centres and taking into account the difficulties of treatment in HBO it is concluded that for advanced carcinoma of the cervix the addition of HBO to radiotherapy is not clinically worthwhile. Radiation-induced brachial plexopathy (RIBP) is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is known to promote healing of tissue rendered ischaemic by radiotherapy, but is untested in RIBP.
                Thirty four eligible research volunteers suffering from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO2 group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibres, was selected as the primary endpoint.
                Pre-treatment neurophysiological tests were grossly abnormal in the affected hand compared to the unaffected hand in both HBO2 and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months post-treatment. However, normalization of the warm sensory threshold in two of the HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial proportion of affected individuals, although improvements in warm sensory threshold offer some suggestion of therapeutic effect. Improvement in long-standing arm lymphoedema was not anticipated, and justifies further investigation. In a previous pilot study, we demonstrated that adjunctive treatment with hyperbaric oxygen (HBO) appears to be feasible and safe in patients with acute myocardial infarction (AMI) and may result in an attenuated rise in creatine phosphokinase (CPK), more rapid resolution of pain and ST changes. This randomized multicenter trial was organized to further assess the safety and feasibility of this treatment in human subjects. Patients with an AMI treated with recombinant tissue plasminogen activator (rTPA) or streptokinase (STK), were randomized to treatment with HBO combined with either rTPA or STK, or rTPA or STK alone. An analysis included 112 patients, 66 of whom had inferior AMIs (p = NS). The remainder of the patients had anterior AMIs. The mean CPK at 12 and 24 h was reduced in the HBO patients by approximately 7.5% (p = NS). Time to pain relief was shorter in the HBO group. There were 2 deaths in the control and 1 in those treated with HBO. The left ventricle ejection fraction (LVEF) on discharge was 51.7% in the HBO group as compared to 48.4% in the controls (p = NS). The LVEF of the controls was 43.4 as compared to 47.6 for those treated, approximately 10% better (no significant difference). Treatment with HBO in combination with thrombolysis appears to be feasible and safe for patients with AMI and may result in an attenuated CPK rise, more rapid resolution of pain and improved ejection fractions. More studies are needed to assess the benefits of this treatment. Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT).
                From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up.
                On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC H&N35 Dry Mouth (p = 0.009), EORTC H&N35, Sticky Saliva (p = 0.01), PSS Eating in Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001).
                Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth. To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC).
                Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors).
                This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072).
                With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication.
Despite the limited amount of clinical research available, it appears that HBO therapy in irradiated patients requiring dental implants may not offer any appreciable clinical benefits. There is a definite need for more RCTs to ascertain the effectiveness of HBO in irradiated patients requiring dental implants. These trials ought to be of a high quality and reported as recommended by the CONSORT statement (www.consort-statement.org/). Each clinical centre may have limited numbers of patients and it is likely that trials will need to be multicentred.