Prolongation of latency or overall treatment time by unplanned radiation pauses. The clinical importance of compensation

BACKGROUND AND PURPOSE: Local tumor control after radiotherapy does not only depend on total dose, dose per fraction and physical parameters but also on the time interval between surgery and begin of radiotherapy and on overall time of fractionated irradiation. This study summarizes the evidence for an impact of delay and overall time of radiotherapy on locoregional tumor control. METHODS: Published reports of the last 30 years were reviewed for evidence of a time factor, i.e., for an influence of overall treatment time on local tumor control. Overall, 33 nonrandomized studies and twelve randomized trials addressing this question were identified. RESULTS: Prolongation of waiting time between surgery and radiotherapy, dependent on tumor type and residual burden, decreases local control. Postoperative radiotherapy should be initiated early, whenever medically appropriate. Almost all nonrandomized and randomized trials indicate that prolongation of overall time of fractionated irradiation decreases local tumor control, particularly of squamous cell carcinoma of the head and neck and cervix, but also of non-small cell and small cell lung cancer. In these tumors prolongation of overall treatment time by 1 week results in a decrease of local control between 1-16%. CONCLUSION: Prescription of radiotherapy may not be limited to total dose and dose per fraction, but needs to include the parameter overall treatment time. Unscheduled treatment interruptions such as holidays, machine breakdown or patient-related factors, leading to protraction of the overall treatment time, decrease the chance of cure for the patient. Therefore, unplanned gaps need to be compensated by appropriate measures such as additional fractions at weekends or by applications of a second fraction per day.