Biomarkers of sensitivity to fraction size in curative radiotherapy
Research type
Research Study
Full title
Biomarkers of sensitivity to fraction size in curative radiotherapy – Radiobiology research involving persons with Li-Fraumeni Syndrome
IRAS ID
162505
Contact name
Navita Somaiah
Contact email
Sponsor organisation
The Institute of Cancer Research
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Radiotherapy is an important part of standard treatment for many cancers, and acts by damaging DNA. We are undertaking this laboratory research study to improve our understanding of the differences between normal and malignant tissues in how they repair radiotherapy-induced damage.
The total dose prescribed in curative radiotherapy is delivered as a series of small daily doses, called fractions. As a general rule, cancers respond to the total dose more strongly than to the size of daily fractions used to deliver it. This contrasts with the response of late-reacting, dose-limiting healthy tissues, which are sensitive both to the total dose and to the fraction size. These differences underpin the standard use of many small fractions of radiotherapy, to deliver the highest total dose tolerated by patients and, thereby, ensuring the greatest impact on their cancers. However, randomised clinical trials led by RM/ICR over the last 20 years provide very good evidence that this does not hold true for women with breast cancer. In fact, a smaller number of larger fractions have advantages both in terms of reducing side effects and increasing anti-tumour activity. This finding has led to a change in international practice, with the consensus now in favour of delivering a lower total dose of radiation in fewer, larger fractions over a shorter overall treatment time. The current UK randomised trial tests a 1-week schedule of curative radiotherapy against the standard 3-week regimen, which replaced the 5-week standard in use prior to 2009. Larger fractions are not a solution for all cancers, and there is a pressing need to understand the molecular mechanisms of radiotherapy damage and repair before we can tailor treatment to the individual patient.
Our previous research has shown that the type of DNA repair pathway the cell uses to repair damage induced by radiation may influence sensitivity of the cell to the daily dose of radiation. TP53 is an important gene that is responsible for stopping normal cells from dividing following radiation exposure, thereby allowing them time to repair the radiation-induced damage to their DNA. People with Li-Fraumeni syndrome have a defect in this gene. This gene is also mutated in several cancers. With this project we are seeking to harvest fibroblasts, a type of normal connective tissue cell, from small skin-punch biopsies of TP53 mutation carriers in order to study the response that this key gene may have on the effect of different radiation fraction sizes used in the clinical setting.
REC name
Wales REC 4
REC reference
14/WA/1212
Date of REC Opinion
24 Nov 2014
REC opinion
Further Information Favourable Opinion