Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Reliability of Time to Exhaustion Treadmill Running as a Measure of Human Endurance Capacity.

Little if any research has examined the variability in time to exhaustion (TTE) during submaximal treadmill running. This study investigated the test-retest reliability of submaximal treadmill TTE as a measure of endurance capacity. 16 endurance-trained males (n=14) and females (n=2) completed a run to exhaustion at 70% V̇O2max (T1) and repeated the same run 3 weeks later (T2). At 30-min intervals during each run, expired gas, heart rate (HR) and ratings of perceived exertion (RPE) were collected. Mean ± SD TTE was 96 ± 20 min in T1 vs. 101 ± 29 min in T2 (P=0.3). The mean ± 95% confidence intervals (CI) of the coefficient of variance (CV) was 5.4% (1.4-9.6). The average intraclass correlation coefficient (± 95% CI) was 0.88 (0.67-0.96) between trials. The respiratory-exchange ratio was not different between trials, T1: 0.87 ± 0.1 and T2: 0.89 ± 0.1 (P>0.05) and neither was total whole-body carbohydrate oxidation (2.1 ± 0.4 g·min(-1) and 2.3 ± 0.6 g·min(-1)), fat oxidation (0.6 ± 0.2 g·min(-1)), HR (178 ± 8 and 175 ± 7 beats·min(-1)) or RPE (17 ± 3 and 16 ± 3). These results suggest that use of prolonged treadmill-based TTE can be a reliable research tool to assess human endurance capacity in aerobically-trained men and women.