Hyperfractionated radiotherapy of human tumors: Overview of the randomized clinical trials

Purpose : Hyperfractionation (HF) is the altered fractionation schedule most frequently studied in clinical Phase III trials. In this overview, surviving fractions, rates of complete responses, and estimates of the long-term locoregional tumor control probabilities after HF and conventional fractionated irradiation (CF) available from the various reports were compared. Methods and Materials : A metaanalysis was performed of the randomized studies on hyperfractionation vs. conventional fractionation published since 1980 on different tumor types in various locations. : Compared with CF, HF significantly reduced the odds of death for patients with head and neck tumors (three studies, odds ratio 0.48 (0.40-0.58), p < 0.0001) and bladder cancer (two studies, odds ratio 0.53 (0.36-0.78), p = 0.001), while there was a trend in nonsmall cell lung cancer (three studies, odds ratio 0.69 (0.51-0.95), p = 0.02), and malignant gliomas (three studies, odds ratio 0.67 (0.48-0.93), p = 0.02). The probability of long-term logo-regional control of head and neck tumors was significantly enhanced after HF (four studies, odds ratio for loco-regional recurrence or related events 0.35 (0.28-0.45), p < 0.0001). In trials on head and neck tumors and bladder cancer, complete responses were seen more often after HF compared with CF (odds ratio for failure of complete response: 0.43 (0.32-0.57), p < 0.0001, and 0.43 (0.27-0.70), p = 0.0007). Conclusions : This overview demonstrates that the effectiveness of radiotherapy is consistently higher for HF than for CF. The assumption that tumors have a small effective fractionation sensitivity (α/β > 5 Gy) seems to be fulfilled especially for head and neck cancers.