Ultrafractionation does not improve the results of radiotherapy in radioresistant murine DDL1 lymphoma

Background and purpose: Low-dose hyperradiosensitivity (HRS), i.e., a relatively higher efficacy of doses ≤0.5 Gy compared to doses >1 Gy, has been shown in a number of tumor cell lines in vitro. Therefore ultrafractionated irradiation, i.e., application of very low doses per fraction, has been proposed to improve the effects of radiotherapy. The present study investigates ultrafractionation (UF) in radioresistant murine DDL1T-cell lymphoma in mice. Material and methods: UF was performed with 0.4 Gy per fraction, three fractions per day at 7 days per week, and conventional fractionation (CF) with 1.68 Gy per fraction, one fraction per day at 5 days per week. Tumor growth delay was evaluated for 2, 4 and 6 weeks of irradiation as time that tumors needed to reach fivefold the starting volume (GDV5). Results: GDV5 was not significantly different between UF and CF. The composite median relative GDV5 calculated for all tumors irradiated in the present study was 1.00 [95% confidence interval 0.99; 1.08] in the CF and 0.99 [0.92; 1.01] in the UF arm (p=0.24). Conclusion: UF was not more efficient than CF in DDL1 tumors. Taken together with previous experiments on human A7 glioblastoma, which showed a negative effect of UF on local tumor control, the preclinical data obtained in this laboratory so far do not support the use of ultrafractionated schedules in radiotherapy. (orig.)