Possible implications of recent radiobiological observations for tumour-dose-fractionation schedules.

Abstract

Data have been published recently (7, 11–13, 18, 19) concerning the log survival curves for a number of mammalian cells in vitro and in vivo which, in vitro, included a variety of malignant and non-malignant cell types of human origin (19). From the sum total of these results, it is probable that the mean lethal dose of radiation for cell populations in well oxygenated environments may prove to be a species characteristic only insignificantly affected by cell type or by transformation of a cell type to the malignant state (13). When the cells studied are anoxic, the log survival curve obtained is still linear but its slope shows that these cells are more radioresistant than the well oxygenated cells by a factor of about 2.3 (12). These survival curves are essentially a measure of the reproductive integrity (capacity for infinite growth) of the cells following irradiation. It is this faculty of cells which is the core of the problem of radiotherapy of tumours, and it has been suggested (13) that it might be well worthwhile to consider tumour-dose requirements for the sterilization of a wide variety of tumours—in terms of a single mean lethal radiation dose—approximately 130 r, 250-kv x-rays, or its biological equivalent of other high-voltage radiation. A number of workers to whom this fundamentally simple approach has been suggested have been very ready to produce reasons why it cannot hope to be successful. But even if some of the objections are valid, it still seems useful to investigate what kind of considerations are involved and how they may influence a radiotherapeutic technique—if only because, after many years of empirical radiotherapy, we are still faced with many inexplicable facts, and with patients for whom the end-results still call for much improvement. A “new look” at the subject in terms of this new data can hardly do harm. Some indeed have commenced to take this “new-look,” as, for example, Gray (10) and Munro and Gilbert (17). Hewitt (14) in particular has been concerned with some of the avenues that may be followed, especially with reference to cell numbers in tumours, tumour-doubling times, dose fractionation, and the effects of the presence of anoxic tumour cells. Also, on the basis of the survival curves for mammalian cells, in particular those aspects which affect recovery (7), some problems of dose fractionation in radiotherapy have been considered by Elkind (8) and by Lajtha, Oliver, and Ellis (15). It is the purpose of this paper to present some other aspects of the implications of the survival curve data for radiotherapy, particularly with reference to dose fractionation and the possible consequences of anoxic cells in the treated tumour.