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

1 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). 2 METHODS AND MATERIALS Between April 1974 and December 1975, 48 patients with locally advanced unr esected SCCHN, referred for primary radiation therapy, were randomized to r adiation delivered in air in two fractions of 12.65 Gy over 21 days to a to tal 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 w as administered under general anesthesia to minimize patient discomfort and potential problems with seizures associated with rapid compression to 4 at mospheres. Patients were monitored regularly by the radiation oncologists f or toxicity, response, local control, and survival. The original hospital r ecords, radiation records, and hyperbaric treatment logs were recently revi ewed, and all data were entered onto a computerized database for the curren t analysis. The results of this trial have not previously been published. 3 RESULTS The air and HBO-4 arms were evenly matched with respect to age, sex, perfor mance status, hemoglobin level, primary site, and stage of disease. Acute t oxicities were acceptable with no significant differences between the two t reatment arms. A trend toward excess severe late complications were noted i n the hyperbaric arm (12 vs 7). There was a highly significant difference i n complete clinical responses between the two arms, with 21/25 in complete clinical responses in the HBO-4 arm compared with 13/25 in complete clinica l 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 surviva l, distant metastasis, or second primary tumors. 4 CONCLUSIONS Long-term outcome from this historical randomized trial demon strate substantial improvements in response rate with the use of HBO-4. The hypofractionation scheme used in the trial resulted in relatively low loca l control and high complication rates in this group of patients with very a dvanced SCCHN. However, these results support the theory that radioresistan t 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.