BACKGROUND AND PURPOSE: The @entity400 ( @entity400 ) @entity135 fractionation schedule delivered 54 Gy in 36 fractions on 12 consecutive days and this was compared in a randomised controlled trial with conventional fractionation delivering 66 Gy in 33 fractions over 6-7 weeks. @entity1 receiving @entity400 experienced statistically significantly less treatment-related morbidity after 6 months than @entity1 receiving conventional fractionation. However, this improved tolerance was much less than anticipated from existing knowledge of dose-fractionation effects on late-responding normal tissues. Here, the experience from the @entity400 study is analysed and repair halftimes for three types of late treatment-related morbidity of @entity1 tissues are estimated. @entity1 AND METHODS: The @entity400 trial was open for @entity1 accrual from March 1990 to April 1995 and a total of 918 @entity1 in 11 participating centres were randomised. All @entity1 were followed at regular intervals for a minimum of 5 years or until the time of @entity204 . At each follow-up, a number of treatment-related morbidity items were evaluated and scored prospectively. Data for three late endpoints are analysed here: @entity4 , @entity8721 and subcutaneous @entity82 . Differences in the incidence of these endpoints in the two trial arms were quantified by means of the ratio of hazard rates in a Cox proportional hazards model. Monte Carlo sampling was performed from distributions of fractionation sensitivity (quantified by the alpha/beta-ratio) and steepness of the dose-response curve (quantified by the normalised dose-response gradient, gamma50) with means and standard deviations derived from the literature. Each pair of values were used to convert a Monte Carlo sampled estimate of the difference in biological effect into an estimate of the repair halftime. From the distribution of 1000 Monte Carlo samples, the mean repair halftime and its 95% confidence interval were estimated. RESULTS: The estimated repair halftimes, with 95% confidence intervals in parentheses, were 4.9 h (3.2, 6.4) for @entity4 , 3.8 h (2.5, 4.6) for @entity8721 and 4.4 h (3.8, 4.9) for subcutaneous @entity82 . Calculations show that these repair halftimes are consistent with the observations from two published randomised controlled trials of altered fractionation in @entity135 , the EORTC 22791 and 22851 trials. CONCLUSIONS: These long repair halftimes for late effects in @entity1 normal tissues have to be considered in order to gain the full benefit from fractionation schedules employing multiple fractions per day.

Repair halftimes estimated from observations of treatment-related morbidity after XXXX or conventional radiotherapy in @entity135 .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'human', 'patient', 'PATIENTS'] @entity135 :: ('MESH:D006258', 'Disease') :: ['head and neck cancer'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity8721 :: ('MESH:D013684', 'Disease') :: ['skin telangiectasia'] @entity4 :: ('MESH:D004487', 'Disease') :: ['laryngeal oedema'] @entity400 :: ('MESH:D014202', 'Disease') :: ['Continuous Hyperfractionated Accelerated Radiotherapy', 'CHART'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death']
@entity400 :: (MESH:D014202,Disease) :: ['CHART']
