Establishment of a Radiogenomics Consortium
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY, USA Radiotherapy and Oncology
(Impact Factor: 4.36).
04/2010; 94(1):117–118. DOI: 10.1016/j.radonc.2009.12.007
Available from: Navita Somaiah
- "Such biomarkers would enable a personalised prediction of radiotherapy efficacy. If combined with personalised predictors of radiation toxicity including radiogenomic markers , both sides of the therapeutic ratio of radiotherapy for localised prostate cancer would be improved. The lethality of radiotherapy is centred on the creation of chromosomal lesions including DNA double strand breaks (DSB), which are particularly lethal when they cluster in close physical proximity to each other . "
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ABSTRACT: Localised prostate cancer, in particular, intermediate risk disease, has varied survival outcomes that cannot be predicted accurately using current clinical risk factors. External beam radiotherapy (EBRT) is one of the standard curative treatment options for localised disease and its efficacy is related to wide ranging aspects of tumour biology. Histopathological techniques including immunohistochemistry and a variety of genomic assays have been used to identify biomarkers of tumour proliferation, cell cycle checkpoints, hypoxia, DNA repair, apoptosis, and androgen synthesis, which predict response to radiotherapy. Global measures of genomic instability also show exciting capacity to predict survival outcomes following EBRT. There is also an urgent clinical need for biomarkers to predict the radiotherapy fraction sensitivity of different prostate tumours and preclinical studies point to possible candidates. Finally, the increased resolution of next generation sequencing (NGS) is likely to enable yet more precise molecular predictions of radiotherapy response and fraction sensitivity.
- "There is too much discovery and too little validation that involves assessment in multiple independent cohorts and assessment of reproducibility. A consortium approach can increase the size and quality of cohorts studied, for example the Radiogenomics Consortium  that is underpinning the discovery of genetic markers of individual radiosensitivity . The development of guidelines for reporting radiotherapy biomarker studies is also needed . "
- "Information from GWAS of other phenotypes suggest that the allelic architecture underlying radiosensitivity will include a spectrum ranging from rare, highly penetrant to low-risk common alterations . The increasing recognition that GWAS must include tens or even hundreds of thousands of patients [56e68] led to the establishment of a radiogenomics consortium in 2009 . The consortium created a vital link between existing collaborative groups [64,66,70e73]. "
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ABSTRACT: There is considerable variation in the level of toxicity patients experience for a given dose of radiotherapy, which is associated with differences in underlying individual normal tissue radiosensitivity. A number of syndromes have a large effect on clinical radiosensitivity, but these are rare. Among non-syndromic patients, variation is less extreme, but equivalent to a ±20% variation in dose. Thus, if individual normal tissue radiosensitivity could be measured, it should be possible to optimise schedules for individual patients. Early investigations of in vitro cellular radiosensitivity supported a link with tissue response, but individual studies were equivocal. A lymphocyte apoptosis assay has potential, and is currently under prospective validation. The investigation of underlying genetic variation also has potential. Although early candidate gene studies were inconclusive, more recent genome-wide association studies are revealing definite associations between genotype and toxicity and highlighting the potential for future genetic testing. Genetic testing and individualised dose prescriptions could reduce toxicity in radiosensitive patients, and permit isotoxic dose escalation to increase local control in radioresistant individuals. The approach could improve outcomes for half the patients requiring radical radiotherapy. As a number of patient- and treatment-related factors also affect the risk of toxicity for a given dose, genetic testing data will need to be incorporated into models that combine patient, treatment and genetic data.
Copyright © 2015. Published by Elsevier Ltd.
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