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.
PURPOSE: 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). METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.