Continuous, hyperfractionated, accelerated radiotherapy (CHART).

The main variables in a course of radiotherapy are the number of fractions, the dose per fraction, the total dose' given and the overall duration of treatment. Radiotherapists endeavour to employ a combination which will achieve the maximum tumour control with the minimum of normal tissue damage. At each centre in the United Kingdom regimes are employed in curative treatment that are based upon clinical experience, practical considerations and local tradition. Although,, in nearly all, daily treatment is given on five days of the week, the number of fractions ranges from 15 to 35, the individual dose from 1.8 to 3.4Gy, the total dose from 50 to 70 Gy and the overall duration from 3 to 7 weeks. An accumulation of data from the laboratory and from the clinic now allows some explanation of the relationship between these variables (Withers et al., 1982, 1988; Trott & Kummermehr, 1984; Denekamp, 1986; Fowler, 1986; Tubiana, 1988). In human tumours it has been possible to determine, using flow cytometry, not only the percentage of cells in S phase, but also the duration of S phase, and hence the potential doubling time, by giving an intravenous administration of bromodeoxyuridine 4-8 h before tumour sampling. Using this technique half of the human tumours studied showed a potential to double their cell number in 5 or fewer days (Begg et al., 1985, 1988; Wilson et al., 1985, 1988). It is probable that the cells which survive the initial treatments of a course of radiotherapy will repopulate rapidly and replace those that have been killed. It follows that the longer the overall duration of treatment the greater must be the chance for repopulation to be a cause of failure. Turning to the normal tissues, we now know that the giving of a course of radiotherapy in many small individual doses may spare late damage, for injury to the critical supporting connective tissue is minimised under these conditions (Withers et al., 1982; Thames, 1988). This knowledge may explain why different regimes may give similar tumour control and morbidity; however, it has also led to clinical exploration to develop new regimes which might bring a real advantage in tumour control. In order to shorten the overall duration of radiotherapy and use a small individual dose per fraction, more than one treatment must be given on each day. There are now a number of completed and ongoing clinical studies using multiple treatments in one day and experience has already shown that a normal dose increment of 2 Gy cannot be maintained while giving accelerated treatment. There are problems with the tolerance of normal tissues and if a full tumour dose is given early reactions may not heal and will continue on to late morbidity (Peracchia & Salti, 1981; Van den Bogaert et al., 1982; Dische & Saunders, 1988). To overcome this, many workers have interrupted their accelerated treatment in order to allow for normal tissue recovery (Van den Bogaert et al., 1982; Wang et al., 1986; Dische & Saunders, 1988). The rest periods have commonly been between 2 and 4 weeks but these, and also the weekend gap between the last treatment on Friday and the first on