Experiments have been carried out to compare the skin reactions in pigs produced by various regimes of fractionated irradiation with X rays, extending up to 28 days. A total of 27 X-ray fields were applied to two pigs. The results show that the major factor which determines the skin response is the size (or number) of the fractions, i.e. the shape of the dose—effect curve. This factor is found to explain approximately five-sixths of the increase of total dose required to produce a given reaction when the dose is divided into five fractions. The remaining one-sixth of the increase is due to tissue repair or repopulation occurring between five and 28 days. The implication in radiotherapy is as follows. If fractionated treatments using fewer and larger fractions are given over the same overall time as a "daily" regime, it is suggested that care must be taken to reduce the total dose below that used in the daily regime, in order to avoid greater skin damage.
Cadmium sulphide crystals used as radiation detectors pass currents which are three orders of magnitude greater than those in p-n junction detectors. However, the response times in CdS are several seconds long for exposure rates less than about 30 roentgens per hour of gamma-rays. Very long build-up times due to long storage in the dark can be avoided by " priming " with a constant, very low, background radiation to keep the traps partially filled. Further large reductions in response times at low exposure rates can be obtained by " biassing " with a constant background of 0·5-3 roentgens/hour. The consequences and limitations of these methods are discussed and some applications are described.
Three sets of investigations were carried out, using (1) the leakage of 131I-HSA (labelled human serum albumin) through the intestinal wall of rats as a measure of gut damage, (2) skin reactions in rats in order to compare with skin reactions in pigs, and (3) the slowing up of the passage of a barium meal through the stomach in rats, as an analogue to radiation sickness. Intestinal injury is known to be the main cause of death in animals given fast neutron doses of 150–300 rads. X rays, on the other hand, give rise to death by marrow injury, at doses in the LD50 range. In assessing the possible dangers of high neutron doses to various tissues, it is therefore important to include investigations on the RBE of intestinal injury. The LD50 in 30 days obviously cannot be used, as the mechanisms causing death by neutrons and X rays are different, although if the LD50 before eight days were used it would be possible to obtain an RBE for intestinal death. We have used a method which did not require lethal irradiations, and which gave a reasonably practical index of injury in the intact animal without extrapolation from simple systems. The mechanism of serious radiation injury is the depopulation of the intestinal epithelium at about three days after irradiation. The lining of the gut then becomes less effective as a selectively absorbing membrane for electrolytes and proteins and as a bacterial barrier.
Fast neutrons were used therapeutically in California between 1937 and 1943, and the disadvantage of the long-term skin damage was mentioned in the introductory paper. Robert Stone and his collaborators treated 249 patients with the fast neutron beams from the 37 in. and 60 in. Berkeley cyclotrons. Accounts of the work and the clinical results obtained have already been published (Stone, Lawrence and Aebersold, 1940; Stone and Larkin, 1942; Stone, 1948) and only the salient facts will be summarised here. All the patients treated, except one, suffered from advanced cancer and were considered incurable by any conventional technique. The exception, a patient with a laryngeal tumour, was suitable for treatment by conventional radiation, but himself elected to have neutron therapy; he remained free of disease for at least six years. This work was not a controlled comparative trial of fast neutrons and X or γ rays. The primary tumours were of varied histology and originated in many different anatomical sites, the number in any one group being too small for any statistically reliable evaluation of the results. A substantial proportion of the patients had had previous treatment either by radiation or by surgery. Initially the 37 in. cyclotron was used and single treatments were given. When the 60 in. cyclotron became available, fractionated treatments extending over three to nine weeks were given. The cyclotrons operated erratically, making it necessary to vary the daily doses, the number of fields treated per day, the total dose and the overall time.