MULTIVARIATE DETERMINANTS OF RADIOCURABILITY .1. PREDICTION OF SINGLEFRACTION TUMOR-CONTROL DOSES

Purpose: The relationship between various laboratory determinants of r adiocurability considered alone and in combination, and the observed 5 0% tumor control dose, has been examined in rodent and xenografted hum an tumors. Methods and Materials: The single fraction 50% tumor contro l dose (TCD50) under normal and clamp hypoxic conditions, 50% tumor ce ll transplant dose (Td(50)), and in vitro estimated tumor cell radiose nsitivity parameters, were determined in each of six tumor types (four isografted murine and two xenografted human tumors). Subcutaneous tra nsplant sites and identical or similar tumor generations were used for both the Td(50) and TCD50 studies. Radiosensitivity parameters were o btained using the clonogenic assay, after allowing cells to enter the active growth phase to recover from trypsin induced alterations of cel l radiosensitivity. Both control and irradiated cells were multiplicit y corrected. Results: No single parameter (InTd(50), hypoxic fraction, or intrinsic radiosensitivity) correlated with the observed tumor con trol doses under aerobic or hypoxic conditions. However, when consider ed in combination, clonogenic fraction (estimated by Td(50)(-1)), and intrinsic radiosensitivity, predicted the rank-order of tumor control doses with a significant degree of accuracy, and tumor hypoxia influen ced the value of the control dose. All parameters were demonstrated to be significant determinants of radiocurability, with substantial tumo r to tumor variation in the relative importance of each. For the six t umor types, the combined laboratory determinants predicted 50% tumor c ontrol doses which differed from the observed TCD(50)s by an average o f approximately 9 Gy under hypoxic conditions. Conclusion: The results obtained demonstrate: (a) the necessity of simultaneously considering all determinants of radiocurability if the role of a single determina nt is to be assessed; (b) laboratory determinants may accurately predi ct tumor radiocurability.