PURPOSE: Low-dose hyperradiosensitivity (HRS) has been demonstrated in numerous cell lines in vitro, including a number of radioresistant @entity1 @entity11 cell lines such as A7. The aim of our experiment was to show whether HRS can be exploited by using ultrafractionated irradiation (UF) to improve local control of A7 @entity5 growing in @entity19 . Extrapolation of the in vitro results predict a 3.7-fold difference in the efficacy of UF compared with @entity7617 ( @entity7617 ). MATERIAL AND METHODS: Subcutaneuously growing A7 @entity5 were irradiated either with UF (126 fractions in 6 weeks, 0.4 Gy per fraction) or @entity7617 (30 fractions in 6 weeks, 1.68 Gy per fraction). The total dose was 50.4 Gy in both experimental arms. Fractionated irradiations were given under ambient conditions and followed by graded top-up doses under clamp @entity519 . Endpoints were @entity5 growth delay and @entity5 control 180 days after the end of treatment. RESULTS: UF resulted in a significant decrease of @entity5 growth delay and in a significant increase of the top-up TCD(50) compared with @entity7617 (40.0 Gy [95% CI 29; 61 Gy] versus 28.3 Gy [24; 35 Gy], p=0.047). CONCLUSIONS: Despite a pronounced HRS phenomenon in vitro, UF was significantly less effective than @entity7617 in A7 @entity1 @entity11 in @entity19 . These results neither disprove the existence of HRS nor do they exclude a possible clinical value of UF. The findings rather indicate that simplistic extrapolation from results obtained after single-dose exposure or few fractions in vitro is not sufficient to predict outcome of UF in vivo and that comprehensive evaluation of novel treatment options in animal models continues to be an essential requirement for clinical translation.

Ultrafractionation in A7 @entity1 @entity11 in XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity7617 :: ('MESH:C563514', 'Disease') :: ['CF', 'conventional fractionation'] @entity19 :: ('10090', 'Species') :: ['nude mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['local tumour', 'tumours', 'tumour'] @entity11 :: ('MESH:D005910', 'Disease') :: ['malignant glioma'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxia']
@entity19 :: (10090,Species) :: ['nude mice']
