Biological factors influencing optimum fractionation in radiation therapy.

Optimum fractionation in radiotherapy occurs when tumor control is improved without enhancement of complications. The main influence on choice of overall time, total dose and fraction size is biological: the proliferation status of tumors. For rapidly proliferating tumors, shorter schedules than 6 to 8 weeks are necessary. Optimum overall time is similar to Tk, the time after beginning cytotoxic treatment when rapid proliferation in tumors starts: 21 to 35 days in head and neck tumors. These, and non-small cell lung tumors, have a clonogenic cell doubling time during radiotherapy of about 3 days. New developments in designing optimum schedules for such tumors are presented: carefully regulated hypofractionation (CRH). For slowly proliferating tumors, especially prostate adenocarcinoma, intracellular repair is large, so larger doses per fraction will be necessary. New evidence is presented showing that their alpha/beta ratio may indeed be lower than 3 Gy. For an entirely different reason from that above, hypofractionation should be tested.