The RTGene study was focused on the development and validation of new transcriptional biomarkers for prediction of individual radiotherapy patient responses to ionizing radiation. In parallel, for validation purposes, this study incorporated conventional biomarkers of radiation exposure, including the dicentric assay. Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumors. For the dicentric assay, two samples were taken from each patient: Prior to radiotherapy and before the final fraction. Blood samples were set up using standard methods for the dicentric assay. All the baseline samples had dicentric frequencies consistent with the expected background for the normal population. For blood taken before the final fraction, all the samples displayed distributions of aberrations, which are indicative of partial-body exposures. Whole-body and partial-body cytogenetic doses were calculated with reference to a 250-kVp X-ray calibration curve and then compared to the dose to blood derived using two newly developed blood dosimetric models. Initial comparisons indicated that the relationship between these measures of dose appear very promising, with a correlation of 0.88 (P = 0.001). A new Bayesian zero-inflated Poisson finite mixture method was applied to the dicentric data, and partial-body dose estimates showed no significant difference (P > 0.999) from those calculated by the contaminated Poisson technique. The next step will be further development and validation in a larger patient group.
Bibliographical noteFunding Information:
We thank all the patients and staff who participated in the study from the Royal Marsden NHS Foundation Trust, Sutton. In particular, we thank Drs. Fiona MacDonald (lung), Alison Tree (prostate), Susan Lalonrelle (endometrium), Diana Tait and Shree Bhide (gastrointestinal) for recruiting patients into this study. This work was partly supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Chemical & Radiation Threats & Hazards at Newcastle University in partnership with Public Health England (PHE). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health or PHE. The multi-panel coding and non-coding transcriptional responses as an indicator of individualized responses to radiation effects in radiation therapy patients, RTGene project, received a pilot grant from the Opportunity Funds Management Core of the Centers for Medical Countermeasures against Radiation, National Institute of Allergy and Infectious Diseases (Bethesda, MD) (grant no. U19AI067773) in collaboration with Columbia University (New York, NY). We acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and ICR. The research by MH was supported by the Basque Government through BERC 360 2014–2017 and the Spanish Ministry of Economy and Competitiveness MINECO and FEDER: BCAM Severo Ochoa excellence accreditation SEV-2013-0323.
© 2018. by Radiation Research Society.