Which methods to minimize the time factor are currently substantiated by evidence, which are unproven?

Background: Several experimental studies and randomized clinical trials dem onstrate a decrease of local tumor control with increasing overall treatmen t time of fractionated radiotherapy. Proliferation of clonogenic tumor cell s most likely is the major mechanism underlying this phenomenon. Important progress in radiation oncology might therefore be expected from inhibition of proliferation of clonogenic cells during radiation treatment. Methods: Possibilities to minimize the time factor are briefly discussed. Results and Conclusions: Inhibition of proliferation of clonogenic tumor ce lls during irradiation by simultaneous chemotherapy, by inhibition of signa l transduction pathways that stimulate proliferation, or by pharmacological inhibition of angiogenesis are scientifically interesting but currently no t proven to be effective to counteract the loss of local tumor control with increasing overall treatment of fractionated irradiation. At present, the only established approach is to complete radiotherapy within a short overal l treatment time, e. g. by accelerated fractionation and by prevention or c ompensation of unscheduled treatment gaps.