THE RELATIONSHIP BETWEEN CELLULAR RADIATION SENSITIVITY AND TISSUE-RESPONSE MAY PROVIDE THE BASIS FOR INDIVIDUALIZING RADIOTHERAPY SCHEDULES

There is a wide variation in normal tissue reactions to radiotherapy a nd in many situations the severity of these reactions limits radiother apy dose. Clinical fractionation studies carried out in Gothenburg hav e demonstrated that a large part of the spectrum of normal tissue reac tions is due to differences in individual normal tissue sensitivity. I f this variation in normal tissue reactions is due to differences in i ntrinsic cellular radiosensitivity, it should be possible to predict t issue response based on measurement of cellullar sensitivity. Here we report the initial results of a study aimed at establishing whether a direct relationship exists between cellular radiosensitivity and tissu e response. Ten fibroblasts strains, including four duplicates, were e stablished from a group of patients in the Gothenburg fractionation tr ials who had received radiotherapy following mastectomy. Skin doses we re measured and both acute and late skin changes were observed followi ng radiotherapy, Right and left parasternal areas were treated with di fferent dose fractionation schedules, Clonogenic assays were used to a ssess intrinsic cellular radiosensitivity, and all experiments were ca rried out without prior knowledge of the clinical response, or which s trains were duplicates. Irradiation was carried out using Co-60 gamma- rays at high dose-rate (HDR) of 1-2 Gy/min and low dose-rate (LDR) of 1 cGy/min. A spectrum of sensitivity was seen, with SF2 values of 0.17 -0.28 at HDR and 0.25-0.34 at LDR, and values of D-0.01 of 5.07-6.38 G y at HDR and 6.43-8.12 Gy at LDR. Comparison of the in vitro results w ith the clinical normal tissue effects shows a correlation between cel lular sensitivity and late tissue reactions, which is highly significa nt with p = 0.02. A correlation between cellular sensitivity and acute effects was noted in the left-sided parasternal fields, but not the r ight, This is thought to be coincidental, and without biological signi ficance. Our results suggest that cellular sensitivity might form the basis for the development of an assay system capable of predicting lat e normal tissue effects to curative radiotherapy, which might allow do se escalation in some patients. Increased local control and cure, with unchanged or improved normal tissue complications, could result from such individualised radiotherapy prescriptions.