Hyperbaric oxygen as a radiotherapeutic adjuvant in advanced cancer of the uterine cervix: preliminary results of a randomized trial. Hyperbaric radiation therapy. Preliminary results of a randomized study of cancer of the urinary bladder and review of the "oxygen experience". Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the bladder. The Leeds results for radiotherapy in HBO for carcinoma of the head and neck. Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix. Carcinoma of the cervix: results of a hyperbaric oxygen trial associated with the use of the cathetron. Radiotherapy and hyperbaric oxygen in head and neck cancer. Final report of first controlled clinical trial. Megavoltage radiotherapy in hyperbaric oxygen. A controlled trial. 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. Radiotherapy of advanced carcinoma of the oropharyngeal region under hyperbaric oxygenation. An interim report. Carcinoma of the cervix and the use of hyperbaric oxygen with radiotherapy: a report of a randomised controlled trial. Irradiation with misonidazole and hyperbaric oxygen: final report on a randomized trial in advanced head and neck cancer.
From September 1968 to March 1974, a randomized clinical trial was carried out, using conventional fractionation, i.e., five treatments per week, in 233 patients with advanced cancers of the uterine cervix--Stages IIB, IIA, IIIB and IVA. The age limit was 70 years and all patients had medical clearance. Lymphangiography and, in some patients, an exploratory laparotomy with selective lymphadenectomy, were done prior to treatment to determine the extent of nodal disease. The staging has not been changed either by lymphangiogram or lymphadenectomy findings. A few patients with bulky Stage I and IIA lesions were entered into the trial because of extensive nodal disease demonstrated either by lymphangiogram and/or lymphadenectomy. First, the patients were grouped according to the clinical stage. The secondary stratification was according to the lymphangiogram and/or selective lymphadenectomy findings. The patients were then randomized to air or hyperbaric oxygen within each group. The patients were pressurized in a Vickers chamber at 3 atmosphere absolute, using a 20-minute soak time prior to the irradition. The size of the external beam portal was determined by the status of the nodes. The difference in absolute NED (no evidence of disease) survival rates for both groups as a whole and by stages is not statistically significant. There is no difference in the incidence of failures in the irradiated area between the HPO and air patients. There is no increase in distant metastases in the HP group. It does not seem that the HPO has had an effect on the major complications. However, there was an increase in the incidence of complications with extended fields. The addition of lymphadenectomy had increased the incidence of fatal complications, even with routine pelvic portals. The negative results of this trial with conventional fractioantion should not lead to the conclusion that HPO could not be useful with schemes using a few high dose fractions. nan In a randomized controlled clinical trial of hyperbaric oxygen in the radiotherapy of carcinoma of the bladder a total of 241 cases were contributed by four radiotherapy centres in the United Kingdom. In this trial where in each centre identical radiotherapy was employed for both oxygen and air cases, no benefit was shown with the use of hyperbaric oxygen. Follow-up data at five years are reported for 24 patients with squamous cell carcinoma of the head and neck, included in a randomised prospective MRC study of radiotherapy in hyperbaric oxygen (10 fractions) or air (15 or 20 fractions). Although few, the data show a significant gain in local control (P less than 0.001) and survival (P less than 0.05) with the use of hyperbaric oxygen but no increased tissue reactions or morbidity. In a randomized controlled clinical trial of hyperbaric oxygen in the radiotherapy of advanced carcinoma of the uterine cervix a total of 320 cases were contributed by four radiotherapy centres in the United Kingdom. The use of hyperbaric oxygen resulted in improved local control and survival. The benefit was greatest in patients under the age of 55 who presented with stage III disease. There was a slight increase in radiation morbidity but it seemed that the benefit of hyperbaric oxygen outweighed this increase in morbidity and that there was a true improvement in the therapeutic ratio. 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. We report the results of a prospective controlled trial of the effect of hyperbaric oxygen as an adjuvant in radiotherapy of head and neck cancer. Patients were allocated randomly to treatment in oxygen or air. The radiotherapy in both groups was identical in planning, dose, and fractionation--i.e., 3500 rads in 10 fractions in 3 weeks. There was no difference in the survival rate between the two groups. However, significantly better local tumour control was seen in the hyperbaric-oxygen group, particularly in smaller lesions; there was significantly greater need for salvage surgery in the air group. Radiation effects on normal tissue appeared somewhat greater in the oxygen series, especially on laryngeal cartilage. nan 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. nan A randomised controlled trial of hyperbaric oxygen in the radiotherapy of Stage IIb and III carcinoma of cervix was performed between 1971 and 1980. Apart from an abstract giving an interim report in 1977, results have not been published.
                In a four arm study, 335 patients were randomised to treatment in 10 or 28 fractions, in hyperbaric oxygen or in air. Data is available concerning 327 cases and this has been analysed.
                There was no advantage in tumour control shown with the use of hyperbaric oxygen. There was evidence for an increase in late radiation morbidity when treatment was given in hyperbaric oxygen rather than in air and when, using 10 fractions, a total dose of 45 rather than 40 Gy was achieved. For late intestinal morbidity, the fractionation sensitivity (alpha/beta ratio) was calculated to be 4.3 Gy and the steepness of the dose response curve (gamma50) to be 2.6.
                Hyperbaric oxygen gave no benefit in the treatment of patients with stage IIb and III carcinoma of the cervix treated with radiotherapy using two fractionation regimes. Important data regarding late radiation morbidity has been revealed. One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospective randomized trial to compare conventional irradiation (63.00 Gy in 30 fractions) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen. The drug (2.0 gm/m2) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The results support a previous study and favor the combination at 1 year at better than the 10% level. This regimen could be useful for bulky primary or nodal disease.
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.