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Based on our experience with conventional, daily irradiation, a split-course radiation schedule was introduced in 1978. The schedule, which was based on Cohen's models for squamous cell carcinoma and vascular damage respectively, predicted an improved tumour control and a reduced rate of late complications, e.g. late oedema, if the conventional, daily treatment was replaced by a split-course schedule. The schedule has later been abandoned, but the experience gained from split-course treatment at various dose levels has been analysed and the results compared with those obtained by conventional radiation. The data allowed construction of dose-response curves and estimation of iso-effect doses. Split-course treatment was associated with a significantly reduced therapeutic ratio because, disappointingly, it did not improve tumour control, and the severity of late complications grew. No late complications were avoided by introducing a 3-week pause in the radiation therapy regimen, nor was the tumour response improved despite a 12-Gy increase in total dose. This indicates a significant repopulation corresponding to more than 0.5 Gy/day, equivalent to an up to 100-fold increase of the number of clonogenic tumour cells during the pause--an increase that occurred despite the decrease, clinically, of the tumours during this period.

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