Cell repopulation and overall treatment time.

Prolongation of the overall treatment time in radiotherapy, especially of squamous cell carcinomas of the head and neck, decreases the chances of cure. This is most likely because of the proliferation of surviving clonogenic tumor cells between dose fractions. Between the 3rd and 7th week of conventional radiotherapy of head and neck cancers, on average 0.5 to 0.7 Gy are lost per day by repopulation. As this represents an average value, repopulation may be even more efficient in subgroups of faster tumors. There is little information on repopulation rates during the first 2 weeks of radiotherapy. Prolongation of the overall treatment time in radiotherapy helps to avoid severe side effects from acutely responding tissues, especially oral mucosa. This sparing effect of increasing overall treatment time is mainly caused by the regeneration of mucosal stem cells and transit cells. This repopulation is slow in the first 2 weeks and accelerates dramatically thereafter. The nature of the trigger for acceleration is not known but seems to be related to a critical threshold of acute tissue hypoplasia and the development of the inflammatory reaction of the connective tissue. It is not known whether accelerated tumor repopulation is stimulated by the same or a similar mechanism as the normal epithelium. During accelerated repopulation the oral mucosa is able to compensate a considerably higher proportion of the daily dose fraction than the tumor. These factors have to be taken into account when treatment strategies are designed to cope with the problem of accelerated repopulation.