title: Biomarkers of Tumour Radiosensitivity and Predicting Benefit from Radiotherapy.
abstract: Radiotherapy is an essential component of treatment for more than half of newly diagnosed cancer patients. The response to radiotherapy varies widely between individuals and although advances in technology have allowed the adaptation of radiotherapy fields to tumour anatomy, it is still not possible to tailor radiotherapy based on tumour biology. A biomarker of intrinsic radiosensitivity would be extremely valuable for individual dosing, aiding decision making between radical treatment options and avoiding toxicity of neoadjuvant or adjuvant radiotherapy in those unlikely to benefit. This systematic review summarises the current evidence for biomarkers under investigation as predictors of radiotherapy benefit. Only 10 biomarkers were identified as having been evaluated for their radiotherapy-specific predictive value in over 100 patients in a clinical setting, highlighting that despite a rich literature there were few high-quality studies for inclusion. The most extensively studied radiotherapy predictive biomarkers were the radiosensitivity index and MRE11; however, neither has been evaluated in a randomised controlled trial. Although these biomarkers show promise, there is not enough evidence to justify their use in routine practice. Further validation is needed before biomarkers can fulfil their potential and predict treatment outcomes for large numbers of patients.
authors.affiliation: Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Forker
authors.affiliation: Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK. Electronic address: ananya.choudhury@christie.nhs.uk.
authors.forename: A
authors.initials: A
authors.lastname: Choudhury
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Headington, Oxford, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Kiltie
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000379:methods*; D059467:Transcriptome / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: DNA damage response; molecular signature; predictive biomarker; radiosensitivity; radiotherapy