REQUITE
Research type
Research Study
Full title
Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality-of-life in cancer survivors
IRAS ID
143488
Contact name
Chris Talbot
Contact email
Sponsor organisation
University of Manchester
Research summary
Summary of Research
The study is to trying to predict which patients who have radiotherapy for their cancer are most likely to have side effects. We are interested in side effects that occur about 2 years after treatment (late effects). About half of all cancer patients have radiotherapy as part of their treatment. It is important to give as much radiation to a tumour as possible but increasing the amount of radiation (radiation dose) increases the risk of harming the healthy cells that surround the tumour. Patients vary in how they react to radiation. About 5% of patients (5 out of every 100) are sensitive and have late side effects that affect their quality-of-life. In recent years, researchers developed models and biological tests to try and identify before the start of treatment those patients who are very sensitive. However, the methods are not yet ready to use in the clinic so radiation doses for all patients are currently limited by the doses the most sensitive patients can have. The international REQUITE multicentre observational study is the largest study of its kind, and the information collected will allow researchers to test these models and biological markers so they are good enough to be used on patients. The results from REQUITE should confirm and/or improve current models and biological tests to predict if a patient will have side effects after radiotherapy. If we are successful, then in future we could measure a patient’s radiosensitivity before they start their radiotherapy. The sensitive patients could be given less radiation and other patients more radiation so they are more likely to be cured. This should reduce side effects for all patients, improve quality-of-life and increase the number of patients cured of their cancer.
Summary of Results
REQUITE worked to address an ambitious and urgent need to reduce long-term side effects and improve health-related quality-of-life in cancer survivors who received radiotherapy. The motivation for the project was the need to move away from a one-size-fits-all approach to treatment. Survivorship issues are particularly relevant for radiotherapy as it is an important potentially curative treatment in many cancers. Although many models and biomarkers have been identified that appear to identify patients with an increased risk of long-term side-effects, validation is rare. Progress is hampered because data and samples are not generally collected in routine clinical practice and any datasets available are heterogeneous. Missing and harmonisation of data are problematic. The main achievement of REQUITE was completing an observational study, the largest study of its kind, which is recognised as an exemplar of the type of multi-disciplinary, multi-national work that can and should be carried out in the radiotherapy-related research field.
As planned REQUITE produced standardised case report forms to collect epidemiology, treatment, side-effect and quality-of-life data from patients recruited in 12 main centres in Belgium, France, Germany, Italy, Spain, The Netherlands, UK and the USA. Questionnaires for collecting patient reported Common Toxicity Criteria for Adverse Events were translated into multiple languages and validated for use. Our forms are being shared worldwide to improve the standardisation of data collection. REQUITE succeeded in establishing a centralised database which is accessible on request by other researchers. 4,438 patients with breast, lung or prostate cancer were recruited prospectively. The quality controlled centralised database for electronic data capture and storage contains >100,000 completed case record forms; 11,563 breast photos; 17,107 DICOM and 12,684 DVH files. Raw genotype data are available for 4,634 and imputed data for 4,304 with European ancestry (1,948 breast, 1,728 prostate, 628 lung) patients. In summary, after quality control a total of 2.04 billion genotypes were directly typed, and 55.2 billion imputed genotypes were recorded.
REQUITE succeeded in establishing a centralised biorepository linked to the database, which store DNA and PAXgene tubes that are easily accessible for validating future biomarkers. Genotyping for common genetic variants (single nucleotide polymorphisms) was successful with the data added to the centralised database. As planned, the radiation induced lymphocyte assay was carried out in three centres (France, Germany, UK) with data generated for a sub-set of 1,319 patients.
Validation of models and biomarkers will be completed after REQUITE ends, but trial designs and draft protocols were developed for future interventional studies using them to personalise radiotherapy and reduce risks of long-term side-effects. In addition to planned work, a process was established to provide access to the resource via submission of a concept form, and a public discovery platform to enable researchers to query the REQUITE resource.
The outputs of REQUITE are already serving as a resource for consortium partners and the wider radiotherapy research community. The short-term impact of the project will be a better understanding of side-effects in a multi-national setting. The results will inform stakeholders and increase knowledge of the health burden and of clinical risk factors. Use of the REQUITE resource to validate models and biomarkers and their use in future interventional trials will have a long-term impact on the health-related quality-of-life of cancer survivors.REC name
North West - Greater Manchester East Research Ethics Committee
REC reference
14/NW/0035
Date of REC Opinion
28 Feb 2014
REC opinion
Further Information Favourable Opinion