Treatment time and circadian genotype interact to influence radiotherapy side-effects. A prospective European validation study using the REQUITE cohort.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Webb Adam J, Harper Emily, Rattay Tim, Aguado-Barrera Miguel E, Azria David, Bourgier Celine, Brengues Muriel, Briers Erik, Bultijnck Renée, Chang-Claude Jenny, Choudhury Ananya, Cicchetti Alessandro, De Ruysscher Dirk, De Santis Maria Carmen, Dunning Alison M, Elliott Rebecca M, Fachal Laura, Gómez-Caamaño Antonio, Gutiérrez-Enríquez Sara, Johnson Kerstie, Lobato-Busto Ramón, Kerns Sarah L, Post Giselle, Rancati Tiziana, Reyes Victoria, Rosenstein Barry S, Seibold Petra, Seoane Alejandro, Sosa-Fajardo Paloma, Sperk Elena, Taboada-Valladares Begoña, Valdagni Riccardo, Vega Ana, Veldeman Liv, Ward Tim, West Catharine M, Symonds R Paul, Talbot Christopher J, REQUITE Consortium
Аннотация
METHODS: Clinical and genotype data from 1690 REQUITE breast cancer patients were used with erythema (acute; n=340) and breast atrophy (two years post-radiotherapy; n=514) as primary endpoints. Local datetimes per fraction were converted into solar times as predictors. Genetic chronotype markers were included in logistic regressions to identify primary endpoint predictors.
FINDINGS: Significant predictors for erythema included BMI, radiation dose and PER3 genotype (OR 1.27(95%CI 1.03-1.56); P < 0.03). Effect of treatment time effect on acute toxicity was inconclusive, with no interaction between time and genotype. For late toxicity (breast atrophy), predictors included BMI, radiation dose, surgery type, treatment time and SNPs in CLOCK (OR 0.62 (95%CI 0.4-0.9); P < 0.01), PER3 (OR 0.65 (95%CI 0.44-0.97); P < 0.04) and RASD1 (OR 0.56 (95%CI 0.35-0.89); P < 0.02). There was a statistically significant interaction between time and genotypes of circadian rhythm genes (CLOCK OR 1.13 (95%CI 1.03-1.23), P < 0.01; PER3 OR 1.1 (95%CI 1.01-1.2), P < 0.04; RASD1 OR 1.15 (95%CI 1.04-1.28), P < 0.008), with peak time for toxicity determined by genotype.
INTERPRETATION: Late atrophy can be mitigated by selecting optimal treatment time according to circadian genotypes (e.g. treat PER3 rs2087947C/C genotypes in mornings; T/T in afternoons). We predict triple-homozygous patients (14%) reduce chance of atrophy from 70% to 33% by treating in mornings as opposed to mid-afternoon. Future clinical trials could stratify patients treated at optimal times compared to those scheduled normally.
FUNDING: EU-FP7.