We have measured the biological equivalence of the Clatterbridge neutron therapy beam [p(62)-Be] and the Hammersmith neutron therapy beam [d(16)-Be] using the mouse intestinal crypt assay. The ratio (NDR) of Clatterbridge neutron (n + gamma) dose relative to Hammersmith neutron dose (n + gamma) was found to be 1.2-1.13 over a dose/fraction range of 1.8-9 Gy at 2 cm deep in a Perspex phantom. It is shown that the effectiveness of the Clatterbridge beam was reduced with penetration into the phantom because of hardening of the beam to a maximum reduction of 11% at 12 cm deep in the phantom. The hardening of the beam with depth of penetration will need to be taken into account by clinicians in assessing the tumour dose and tissue tolerance. Relative biological effectiveness values for the Clatterbridge and Hammersmith neutron beams were also measured. All neutron doses for both Hammersmith and Clatterbridge beams are total doses (n + gamma) which comply with the European protocol for neutron dosimetry and include the gamma-ray component of dose.

Chinese hamster V79 cells have been used to assess changes in RBE of the p(62)Be neutron beam at the Clatterbridge Hospital with depth in a phantom and with use of a hydrogenous filter. The cells were exposed at depths of 2 and 12 cm and at a depth of 2 cm with a hydrogenous filter. Two groups of experimenters each conducted two experiments. The ratios of relative biological effectiveness (RBE) at a depth of 12 cm to that at 2 cm were found by the two groups to be 0.99 +/- 0.04 and 0.96 +/- 0.02 (standard errors). The effect of a polythene filter 4.5 cm thick was measured at a depth of 2 cm and the ratio of RBE with and without the filter was found by both groups to be 0.99 +/- 0.02. All the experiments suggest that there may be small effects of beam hardening by depth and filtration but these results are in marked contrast with those obtained using an in vivo system.

Thick plasma samples have been irradiated in air by 2.3 MeV protons for trace elemental analysis by proton-induced X-ray emission spectroscopy. Accurate calibration curves were obtained for Fe, Zn and Sr and detection limits in dry plasma were estimated to be 0.08 PPM for Fe, 0.065 PPM for Zn and 0.12 PPM for Sr. Low temperature ashing of these samples improved the detection limits by a factor of 3 but reduced the precision and resulted in loss of bromine from the plasma. Mass absorption coefficients for low energy X-rays in dry plasma were measured and X-ray attenuation in the sample was found to prevent the detection of trace elements with Z less than 26. The method was used to determine Sr in plasma from a patient with bone disease, the Sr being a non-radioactive bone-seeking tracer element. The results, which were in the 3--13 PPM range, were in good general agreement with the analysis of the same samples by flame photometry.

Survival of reproductive capacity of murine leukaemia P-388 cells was assayed in vivo after the cells had been irradiated in vitro under aerobic or hypoxic conditions with collimated beams of X rays or 16 MeV D-Be fast neutrons at various depths in tissue-equivalent phantom material. The response to X-irradiation was the same in the absence of the phantom and at 8-7 cm depth. The response to fast neutrons under aerobic conditions was unchanged from 0 to 23 cm depth within the phantom. However, under hypoxic conditions, the dose-response curve for fast neutrons became significantly steeper with increasing depth in the phantom. The OER decreased from 2-0 in the absence of the phantom to 1-5 at 15 cm deep.

J. C. Clark, J. H. Fremlin, W. Tanti-Wipawin, N. A. Dyson, A. E. Simpson, D. R. Williams, J. S. Hislop, T. J. Spinks, D. K. Bewley, B. J. Thomas, M. S. Wright, E. Ozbas, D. Vartsky, J. W. Mcmillan and T. B. Pierce, Proc. Anal. Div. Chem. Soc., 1976, 13, 193 DOI: 10.1039/AD9761300193

The International System of Units (SI) was adopted internationally in 1960. In 1968 the Royal Society of Medicine organized a conference of medical editors to discuss the introduction of SI units, but their recommendations did not appear until 1972 (Ellis, 1972). Now another, more comprehensive book on the subject has appeared (Armstrong Lowe, 1975). Nevertheless, few journals have made a complete change to the new system. Why the long delay? In the medical field no doubt writers have held back until the hospitals had changed over internally to the new system.

Results of the first randomized clinical trial to compare the effects of fast neutrons and those of x or gamma rays (photons) in treating patients with advanced tumours of the head and neck are reported. In 37 out of 52 patients treated with neutrons and 16 out of 50 treated with photons the local tumour completely regressed; the tumour later recurred in nine of the 16 photon patients but in none of the 37 neutron patients. The advantages to the neutron-treated patients were seen in tumours of well and poorly differentiated histology and in each site. Complications after treatment did not differ significantly between the groups. Despite these substantial differences in local control of the tumour there were no significant differences in mortality between the series. A detailed study of the effective doses and the response of tumours and normal tissue in each series indicated that the improved results from neutron therapy were due to differences in the biological quality of the beam and not to the rather higher average effective dose in the neutron series. To assess the long-term effects of neutron treatment patients in earlier stages of disease and with smaller tumours should be included in the next phase of the trial.

SummarySkin reactions and late deformities after irradiation of the feet of anaesthetized rats with 7 MeV electrons have been measured for dose-rates between 200 rads/min and 500 krads/min. For dose-rates up to 70 krads/min, there was no alteration in the effectiveness of the radiation, which implies that there is not a rapid form of repair of sub-lethal damage in rat skin. However, when the dose-rate was increased to 500 krads/min, there was a marked decrease in effectiveness. This observation was not made when the feet were anoxic, which implies that there is oxygen depletion at the high dose-rate. For irradiation at 500 krads/min, given in aerobic conditions, the ‘break-away’ point occurred at about 2000 rads, above which the response of the skin was similar to that when it was made anoxic. It was concluded from this observation that the sensitive cells were at a pO2 of 5–10 mm Hg.

An orientation independent dosemeter is reported here using a CaSO4:Tm phosphor powder recently developed in Japan (Yamashita, Nada, Onishi and Kitamura 1968). This phosphor combines very high sensitivity with a small intrinsic response to fast or thermal neutrons. Instead of using encapsulating walls of hydrogeneous substances to supply protons to react with the solid phosphor, the powdered phosphor has been mixed with a hydrogeneous powder (e.g. glucose crystals) in order to eliminate the angular dependence of response.

This article considers the advantages and difficulties of using pions and heavy ions for cancer radiotherapy.

SummaryThe effectiveness of radiation in killing mice within 4–5 days of whole-body irradiation is reduced for mice breathing oxygen during irradiation when the dose-rate is increased above 6 krads/min. The effectiveness of the radiation is not changed if the mice breath nitrogen during irradiation. This is considered to validate the hypothesis that at dose-rates above 6 krads/min the tissue oxygen tension may be reduced by the consumption of oxygen by the radiation products. A reduction in the biological effect of radiation will be observed when the dose is sufficiently high to reduce the oxygen tension in the tissues to levels which give some protection.

Ehrlich mouse ascites cells have been used as a biological dosimeter to check physical methods of measurement of central axis depth doses of a beam of fast neutrons. The cells were irradiated in suspension in Perspex tubes, using air or nitrogen bubbling. Irradiations with fast neutrons under aerobic conditions were carried out at four depths in a tissue-equivalent phantom and in the absence of the phantom. The relative intensities of the radiation under these conditions agreed well with measurements using a special ionisation chamber, provided allowance was made for accompanying γ radiation. The oxygen enhancement ratio was found to be 2·78 with 250 kV X rays and 1·80 with the fast neutron beam. No signicant change of OER was observed for irradiations at 8·7 cm deep in the phantom.

Mice have been irradiated with fast neutrons (mean energy 6 MeV) under normal and hypoxic conditions. Hypoxia was induced by brief periods of nitrogen breathing. Observations of the thymus weight two days later gave an oxygen enhancement ratio of 1·7 ± 0·2. Earlier irradiations with 8 MeV electrons gave an OER of 2·7 ± 0·3. This gives a gain factor of l·6 ± 0·2. The RBE relative to 8 MeV electrons is 2·35 in air and 3·82 in nitrogen.

The proportion of animals surviving four days after whole body neutron irradiation is not altered by giving the radiation in two fractions separated by four to six hours. This result is compared with previously reported data after 250 kV X irradiation when it was found that a dose higher by 400–600 rads was necessary to produce the same killing effect if the radiation was given in two fractions rather than a single dose. This results in a larger RBE (250 kV/neutron) for the fractioned radiation than for single-dose irradiation and any increase in the number of fractions would increase the RBE further. These results may be relevant to the use of neutrons for therapy.

Fifteen fields on one pig were irradiated with 1, 2, 2, 3 and 5 fractions in 1, 5, 2, 3 and 5 days respectively. Skin reactions were recorded up to 80 or 100 days, so that the doses which produced equal reactions could be assessed. Three degrees of damage were analysed for early, medium and late reactions. As an example, the doses to produce one level of reaction over 30–85 days were respectively 2,050, 2,560–2,750, 2,750, 3,360 and 4,060 rads for the fractions listed above. The corresponding values of “DQ” = (Dn — D1)/(n —; 1) were high, 500–700 rads. The values of (Dn − D1)/(n − 1) became smaller with larger numbers of fractions. Two pigs were irradiated to investigate the “reciprocal vicinity” effect. It was found to be small for the field arrangements used, but the sensitivity of pig skin increased in the dorso-ventral direction and corrections were sometimes necessary. Two pigs were irradiated with pairs of equal doses separated by 0 to 24 hours. A recovery pattern was observed similar to that found in cell culture by Elkind and Sutton (1959), but less well resolved. It is not established that skin damage is entirely due to loss of cellular reproductive integrity, but from the practical point of view the empirical relation between dose and skin damage in pigs is similar to that found in patients, and is in agreement with other work on mouse skin and mouse intestinal death, but not with cell survival work on haemopoietic cells.