limits radio~erapy dose. Clinical fractionation studies carried out in Gothenburg have demonstrated that a large part of the spectrum of normal tissue reactions is due to differences in individual normal tissue sensitivity. If this variation in normal tissue reactions is due to differences in intrinsic cellular ra~osensitivity, it should be possible to predict tissue response based on measurement of cellular sensitivity.
Here we report the initial results of a study aimed at establishing whether a direct relations~p exists between cellular radiosensitivity and tissue response. Ten fibroblasts strains, including four duplicates, were established from a group of patients in the Gothenburg fractionation trials who had received radiotherapy following mastectomy. Skin doses were measured and both acute and late skin changes were observed following radiotherapy. Right and left parastemal areas were treated with different dose fractionation schedules. Clonogenic assays were used to assess intrinsic cellular radiosensitivity, and all experiments were carried out without prior knowledge of the clinical response, or which strains were duplicates. h-radiation was carried out using M)Co yrays at high dose-rate (HDR) of l-2 Gy/min and low doserate (LDR) of 1 cGy/min. A spectrum of sensitivity was seen, with SF, values of 0.17-0.28 at HDR and 0.25-0.34 at LDR, and values of D0.0l of 5.07-4.38 Gy at HDR and 6.43-8.12 Gy at LDR. Comparison of the in vitro results with the clinical normal tissue effects shows a correlation between cellular sensitivity and late tissue reactions, which is highly significant with p = 0.02. A correlation between cellular sensitivity and acute effects was noted in the leftsided parastemal fields, but not the right. This is thought to be coincidental, and without biological significance. Our results suggest that cellular sensitivity might form the basis for the development of an assay system capable of predicting late normal tissue effects to curative radiotherapy, which might allow dose escalation in some patients. Increased local control and cure, with unchanged or improved normal tissue complications, could result from such individualised radiotherapy prescriptions.