The European Union funded REQUITE consortium aims to validate predictors of radiotherapy-related adverse reactions to develop clinically useful tools. Potential predictors include clinical and dose parameters, genetic markers, gene expression and the radiation-induced lymphocyte apoptosis (RILA). ; Peer-reviewed ; Publisher Version ; The 37th Meeting of the European-Society-for-Radiotherapy-and-Oncology (ESTRO), Barcelona, SPAIN
Supplementary data to this article can be found online at https://doi.org/10.1016/j.radonc.2019.04.034. ; PURPOSE: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. METHODS: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. RESULTS: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician- (47,025 forms) and patient- (54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade ≥2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). CONCLUSION: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. PATIENT SUMMARY: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short- and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity. ; REQUITE received funding from the European Union's Seventh Framework Programme for research, technological development, and demonstration under grant agreement no. 601826. We sincerely thank all patients that participated in the REQUITE study and all REQUITE staff involved at the following sites: Belgium: Ghent University Hospital; KU Leuven. France: ICM Montpellier, CHU Nîmes (Department of Radiation Oncology, CHU Nîmes, Nîmes, France). Germany: Praxis für Strahlentherapie an der Stadtklinik Baden-Baden; Klinikum Darmstadt GmbH; Zentrum für Strahlentherapie Freiburg; Städtisches Klinikum Karlsruhe; St. Vincentius-Kliniken gAG Karlsruhe; Klinikum der Stadt Ludwigshafen GmbH; Universitätsklinikum Mannheim: Anke Keller and Christiane Zimmermann; Strahlentherapie Speyer. The researchers at DKFZ also thank Dr Sabine Behrens and Kerstin Pieper. Italy: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Candiolo Cancer Institute – FPO, IRCCS. The Netherlands: Sylvie Canisius at Maastro Clinics, Maastricht. Spain: Santiago: Complexo Hospitalario Universitario de Santiago. Ana Vega is supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds (INT15/00070, INT16/00154, INT17/00133; PI16/00046; PI13/02030; PI10/00164), and through the Autonomous Government of Galicia (Consolidation and structuring program: IN607B); Barcelona: The authors acknowledge the Cellex Foundation for providing research facilities and equipment. S. Gutiérrez-Enríquez is supported by the Miguel Servet Program from ISCIII (CPII16/00034). UK: University Hospitals of Leicester NHS Trust, Dr Tim Rattay was funded by a National Institute of Health Research (NIHR) Doctoral Research Fellowship (DRF-2014-07-079); Manchester: Jacki Routledge at Christie NHS Foundation Trust, Manchester. Catharine West, Ananya Choudhury and Rebecca Elliott are supported by NIHR Manchester Biomedical Research Centre and Catharine West is supported by Cancer Research UK (C1094/A18504, C147/A25254); University Hospitals Birmingham NHS Foundation Trust; Derby Hospitals NHS Foundation Trust; Nottingham University Hospitals NHS Trust; Salford Royal NHS Trust. USA: Mount Sinai Hospital, New York; Memorial Sloan Kettering Cancer Center, New York. ; Peer-reviewed ; Publisher Version
