OPTIMUM O2/CO2 RATIO IN RADIOTHERAPY.

Abstract

Numerous experiments have established that the presence of oxygen in the cell at the time of irradiation is an important factor in the determination of response to the dose. Some radiotherapists have accepted this to the extent of making a clinical trial of treating patients in a chamber containing oxygen at high pressure. Putting the oxygen under pressure increases the amount dissolved in the plasma, which then carries more oxygen to the tumor. In an earlier paper, comparison of cure rates in spontaneous tumors in mice showed that more oxygen could also be delivered to the tumor cell by allowing the mice to breathe 95 per cent O2 + 5 per cent CO2 at atmospheric pressure. The vasodilatation and respiratory stimulation of CO2 is probably the explanation. Cure rates were about the same as for oxygen under three atmospheres pressure, but systemic effects, as shown by the number of deaths during the treatment series, were much less with the O2/CO2 mixture. The hazards of high pressure are well known but the toxic effect of oxygen has not received the same attention. Using pure oxygen even at atmospheric pressure increased early deaths although it did not increase cure rates over air. The use of atmospheric pressure O2/CO2 eliminates the complications of both pure oxygen and high pressure and increases cure rates as well. The next question to be answered was that of the optimum fraction of CO2 which should be put in the oxygen for maximum cure rate and minimum systemic effects. To determine this, 279 C3H/HeJ mice with spontaneous mammary adenocarcinomas between 8 and 17 mm. in diameter were treated with x-rays in a chamber containing the gas mixture at atmospheric pressure, with the fraction of CO2 2, 5, 10, or 20 per cent. The mice were assigned at random to one of these. All were given 1,000 r twice a week to 6,000 r in eighteen days. They were all about the same age and weight and tumor size distribution was the same in all groups. The mice were immobilized for treatment by wrapping them in wire mesh, cut away over the tumor. They were shielded from radiation by a heavy sheet of lead, except for the tumor and a margin of 5 mm. around it. They were placed in the chamber, the gas mixture was allowed to flow through it to flush out the air, and treatment was started. The gas continued to flow during treatment so that the fraction of CO2 remained constant. Control of tumor was determined by palpation. The gas mixture used during treatment was not known at the time of examination. The mice were examined weekly so that classification was made within a week of death. Thirteen mice were classed as indeterminate because of obvious geographical miss of the tumor or because it was impossible to come to a clear decision on classification.