The influence of sequence and timing of drugs and radiation on the appearance of normal tissue damage

Summary Acute and delayed normal tissue damage has been investigated in 63 advanced stage testicular non-seminoma patients receiving elective involved-field irradiation after chemotherapy and in 53 patients who had chem- otherapy given for relapse after prior irradiation~ The risk of death from complications due to chemotherapy was 0% and 9.4% (p < 0.025) in the two groups respectively. Gastro-intestinal damage and/or subcutaneous fibrosis was present in 12.6% and 24.5% of patients respectively, although only three patients have serious persisting disability. In patients receiving 35-45 Gy to the retroperitoneum the incidence of normal tissue damage was 0% and 25% (p < 0.001), respectively. In addition to the sequence in which chemotherapy and radiotherapy was delivered, the time interval between completion of radiotherapy and start of chemotherapy was important with 6/6 patients receiving drugs within 2 months of irradiation developing fibrosis. Ab- dominal surgery appeared not to influence the risk of damage. Of nine patients receiving drugs after infra- diaphragmatic and supra-diaphragmatic irradiation two died of neutropenic sepsis.