Preclinical evaluation of pions in vivo : experience at TRIUMF

Abstract

This paper describes the results obtained from in vivo studies of the pion beam at the TRI University Meson Facility (TRIUMF). The studies encompass work (from 1978 to 1986), designed to evaluate the RBE for early and late effects and to assess the importance of X-ray dose rate and treatment volume on these values. Results with early responding tissues, i.e. mouse and pig skin and mouse intestine indicate a pion RBE of about 1.5 in the clinically relevant dose per fraction range of 2–3 Gy. At these doses, RBE appears to be independent of the reference X-ray dose rate. However, at high doses per fraction, the RBE values become increasingly X-ray dose rate dependent. The induction of late effects by pions has been assessed by monitoring the late dermal response of pig skin; late fibrosis was not assessed in this study. The values obtained using the chosen endpoint indicate that the RBE is not significantly higher than that seen in any of the early responding tissues for pion doses as low as 2–3 Gy per fraction. The effect of increasing the treatment volume for pion therapy has been assessed using mouse intestine. The results show that for a constant field size, RBE decreases with increasing peak width. However, if peak width is held constant and field size increased, there is evidence for an increased RBE. Thus, for pion volumes used in clinical treatments where both field size and peak width are increased, the effective RBE may not be that much different from values obtained in animal studies where narrow peak widths and small field sizes are commonly used. The in vivo studies undertaken at TRIUMF have provided a basis for choosing the pion doses to be used in the clinical studies. Indeed the clinical data obtained to date indicate that the RBE value of 1.5 obtained from the preclinical in vivo studies is suitable for skin, brain, colorectum and vagina.