INTRATUMORAL HETEROGENEITY AS A CONFOUNDING FACTOR IN CLONOGENIC ASSAYS FOR TUMOR RADIORESPONSIVENESS

The level of intra-tumoral heterogeneity of cellular radiosensitivity within primary cultures of three carcinomas of the cervix has been est ablished, All three cultures contained clones that varied by as much a s 3-fold in their clinically relevant radiosensitivity (SF2). The leve l of intra-tumoral heterogeneity observed in these cervical tumour cul tures was sufficient to be a major confounding factor to the use of pr e-treatment assessments of radiosensitivity to predict for clinical ra dioresponsiveness. Mathematical modeling of the relative elimination o f the tumour clones during fractionated radiotherapy indicates that, i n two of the three biopsy samples, the use of pre-treatment derived SF 2 values from the heterogeneous tumour sample would significantly over estimate radioresponsiveness, We conclude that assays of cellular radi osensitivity that identify the radiosensitivity of the most radioresis tant clones and measure their relative abundance could potentially inc rease the effectiveness of SF2 values as a predictive marker of radior esponsiveness.