{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T10:32:45Z","timestamp":1793442765977,"version":"4.5.0"},"reference-count":50,"publisher":"Radiation Research Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2020,12,30]]},"abstract":"<jats:p>In this work, individual radiosensitivity was evaluated using DNA damage response and chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) for the prediction of acute toxicities of chemoradiotherapy (CRT) in esophageal cancer patients. Eighteen patients with esophageal cancer were enrolled in this prospective study. Prescribed doses were 60 Gy in 11 patients and 50 Gy in seven patients. Patients received 2 Gy radiotherapy five days a week. PBLs were obtained during treatment just before and 15 min after 2 Gy radiation therapy on the days when the cumulative dose reached 2, 20, 40 Gy and 50 or 60 Gy. PBLs were also obtained four weeks and six months after radiotherapy in all and 13 patients, respectively. Dicentric and ring chromosomes in PBLs were counted to evaluate the number of CAs. Gamma-H2AX foci per cell were scored to assess DNA double-strand breaks. We analyzed the association between these factors and adverse events. The number of \u03b3-H2AX foci before radiotherapy showed no significant increase during CRT, while their increment was significantly reduced with the accumulation of radiation dose. The mean number of CAs increased during CRT up to 1.04 per metaphase, and gradually decreased to approximately 60% six months after CRT. Five patients showed grade 3 toxicities during or after CRT (overreactors: OR), while 13 had grade 2 or less toxicities (non-overreactors: NOR). The number of CAs was significantly higher in the OR group than in the NOR group at a cumulative dose of 20 Gy (mean value: 0.63 vs. 0.34, P = 0.02), 40 Gy (mean value: 0.90 vs. 0.52, P = 0.04), and the final day of radiotherapy (mean value: 1.49 vs. 0.84, P = 0.005). These findings suggest that number of CAs could be an index for predicting acute toxicities of CRT for esophageal cancer.<\/jats:p>","DOI":"10.1667\/rade-20-00234.1","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T15:35:04Z","timestamp":1613748904000},"page":"244-252","source":"Crossref","is-referenced-by-count":9,"title":["Evaluating Individual Radiosensitivity for the Prediction of Acute Toxicities of Chemoradiotherapy in Esophageal Cancer Patients"],"prefix":"10.1667","volume":"195","author":[{"given":"Nobuki","family":"Imano","sequence":"first","affiliation":[{"name":"Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuno","family":"Nishibuchi","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Kawabata","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuha","family":"Kinugasa","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Shi","sequence":"additional","affiliation":[{"name":"Institute of Medical Imaging and Digital Medicine, School of Medical Imaging, Xuzhou Medical University, Xuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiemi","family":"Sakai","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Physiology and Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Ishida","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Physiology and Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Sakane","sequence":"additional","affiliation":[{"name":"Departments of Diagnostic Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Akita","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Murakami","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimio","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Horikoshi","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Nagata","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Tashiro","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"34","doi-asserted-by":"crossref","unstructured":"WW Kam  and RB Banati  \"Free Radic Biol Med.\"  65, \"Effects of ionizing radiation on mitochondria.\" 607 (2013)","DOI":"10.1016\/j.freeradbiomed.2013.07.024"},{"key":"38","doi-asserted-by":"publisher","unstructured":"SV Costes, I Chiolo, JM Pluth, et al.  \"Mutat Res.\"  704, \"Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization.\" 78 (2010)","DOI":"10.1016\/j.mrrev.2009.12.006"},{"key":"23","unstructured":"et al.  \"Cytogenetic dosimetry: applications in preparedness for and response to radiation emergencies.\"  ,  (2011)"},{"key":"19","doi-asserted-by":"crossref","unstructured":"EC Bourton, PN Plowman, D Smith, et al.  \"Int J Cancer.\"  129, \"Prolonged expression of the gamma-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment.\" 2928 (2011)","DOI":"10.1002\/ijc.25953"},{"key":"1","doi-asserted-by":"crossref","unstructured":"TY Seiwert, JK Salama, EE Vokes,  \"Nat Clin Pract Oncol.\"  4, \"The concurrent chemoradiation paradigm\u2013general principles.\" 86 (2007)","DOI":"10.1038\/ncponc0714"},{"key":"2","doi-asserted-by":"crossref","unstructured":"TH Kim, KH Cho, HR Pyo, et al.  \"Int J Radiat Oncol Biol Phys.\"  62, \"Dose-volumetric parameters of acute esophageal toxicity in patients with lung cancer treated with three-dimensional conformal radiotherapy.\" 995 (2005)","DOI":"10.1016\/j.ijrobp.2004.12.025"},{"key":"3","doi-asserted-by":"crossref","unstructured":"J Huang, T He, R Yang, et al.  \"Onco Targets Ther.\"  11, \"Clinical, dosimetric, and position factors for radiation-induced acute esophagitis in intensity-modulated (chemo)radiotherapy for locally advanced non-small-cell lung cancer.\" 6167 (2018)","DOI":"10.2147\/OTT.S174561"},{"key":"4","doi-asserted-by":"crossref","unstructured":"Z Zhang, J Xu, T Zhou, et al.  \"Radiat Oncol.\"  9, \"Risk factors of radiation-induced acute esophagitis in non-small cell lung cancer patients treated with concomitant chemoradiotherapy.\" 54 (2014)","DOI":"10.1186\/1748-717X-9-54"},{"key":"5","doi-asserted-by":"crossref","unstructured":"RB Barriger, AJ Fakiris, N Hanna, et al.  \"Int J Radiat Oncol Biol Phys.\"  78, \"Dose-volume analysis of radiation pneumonitis in non-small-cell lung cancer patients treated with concurrent cisplatinum and etoposide with or without consolidation docetaxel.\" 1381 (2010)","DOI":"10.1016\/j.ijrobp.2009.09.030"},{"key":"6","doi-asserted-by":"crossref","unstructured":"S Wang, Z Liao, X Wei, et al.  \"Int J Radiat Oncol Biol Phys.\"  66, \"Analysis of clinical and dosimetric factors associated with treatment-related pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT).\" 1399 (2006)","DOI":"10.1016\/j.ijrobp.2006.07.1337"},{"key":"7","doi-asserted-by":"crossref","unstructured":"K Tsujino, S Hirota, M Endo, et al.  \"Int J Radiat Oncol Biol Phys.\"  55, \"Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer.\" 110 (2003)","DOI":"10.1016\/S0360-3016(02)03807-5"},{"key":"8","doi-asserted-by":"crossref","unstructured":"SG Chun, C Hu, H Choy, et al.  \"J Clin Oncol.\"  35, \"Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: A secondary analysis of the NRG Oncology RTOG 0617 randomized clinical trial.\" 56 (2017)","DOI":"10.1200\/JCO.2016.69.1378"},{"key":"9","doi-asserted-by":"crossref","unstructured":"B van Oorschot, SE Hovingh, PD Moerland, et al.  \"Int J Radiat Oncol Biol Phys.\"  88, \"Reduced activity of double-strand break repair genes in prostate cancer patients with late normal tissue radiation toxicity.\" 664 (2014)","DOI":"10.1016\/j.ijrobp.2013.11.219"},{"key":"10","doi-asserted-by":"crossref","unstructured":"JB Barber, W Burrill, AR Spreadborough, et al.  \"Radiother Oncol.\"  55, \"Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer.\" 179 (2000)","DOI":"10.1016\/S0167-8140(99)00158-9"},{"key":"11","doi-asserted-by":"crossref","unstructured":"U Hoeller, K Borgmann, M Bonacker, et al.  \"Radiother Oncol.\"  69, \"Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer.\" 137 (2003)","DOI":"10.1016\/j.radonc.2003.10.001"},{"key":"12","doi-asserted-by":"crossref","unstructured":"R Huber, H Braselmann, H Geinitz, et al.  \"Radiat Oncol.\"  6, \"Chromosomal radiosensitivity and acute radiation side effects after radiotherapy in tumour patients\u2013a follow-up study.\" 32 (2011)","DOI":"10.1186\/1748-717X-6-32"},{"key":"13","doi-asserted-by":"crossref","unstructured":"ML Chua, N Somaiah, R A'Hern, et al.  \"Radiother Oncol.\"  99, \"Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy.\" 362 (2011)","DOI":"10.1016\/j.radonc.2011.05.071"},{"key":"14","doi-asserted-by":"crossref","unstructured":"LA Beaton, L Marro, S Samiee, et al.  \"Int J Radiat Biol.\"  89, \"Investigating chromosome damage using fluorescent in situ hybridization to identify biomarkers of radiosensitivity in prostate cancer patients.\" 1087 (2013)","DOI":"10.3109\/09553002.2013.825060"},{"key":"15","doi-asserted-by":"crossref","unstructured":"CN Sprung, M Chao, T Leong, et al.  \"Clin Cancer Res.\"  11, \"Chromosomal radiosensitivity in two cell lineages derived from clinically radiosensitive cancer patients.\" 6352 (2005)","DOI":"10.1158\/1078-0432.CCR-04-1931"},{"key":"16","doi-asserted-by":"crossref","unstructured":"I Nishibuchi, H Suzuki, A Kinomura, et al.  \"Int J Radiat Oncol Biol Phys.\"  89, \"Reorganization of damaged chromatin by the exchange of histone variant H2A.Z-2.\" 736 (2014)","DOI":"10.1016\/j.ijrobp.2014.03.031"},{"key":"18","doi-asserted-by":"crossref","unstructured":"PL Olive  and JP Ban\u00e1th  \"Int J Radiat Oncol Biol Phys.\"  58, \"Phosphorylation of histone H2AX as a measure of radiosensitivity.\" 331 (2004)","DOI":"10.1016\/j.ijrobp.2003.09.028"},{"key":"20","doi-asserted-by":"crossref","unstructured":"HV Goutham, KD Mumbrekar, BM Vadhiraja, et al.  \"Int J Radiat Oncol Biol Phys.\"  84, \"DNA double-strand break analysis by gamma-H2AX foci: a useful method for determining the overreactors to radiation-induced acute reactions among head- and-neck cancer patients.\" e607 (2012)","DOI":"10.1016\/j.ijrobp.2012.06.041"},{"key":"21","doi-asserted-by":"crossref","unstructured":"SE Pouliliou, TS Lialiaris, T Dimitriou, et al.  \"Int J Radiat Oncol Biol Phys.\"  92, \"Survival fraction at 2 Gy and gamma-H2AX expression kinetics in peripheral blood lymphocytes from cancer patients: Relationship with acute radiation-induced toxicities.\" 667 (2015)","DOI":"10.1016\/j.ijrobp.2015.02.023"},{"key":"24","doi-asserted-by":"crossref","unstructured":"L Shi, K Fujioka, J Sun, et al.  \"Radiat Res.\"  177, \"A modified system for analyzing ionizing radiation-induced chromosome abnormalities.\" 533 (2012)","DOI":"10.1667\/RR2849.1"},{"key":"25","doi-asserted-by":"crossref","unstructured":"L Shi, K Fujioka, N Sakurai-Ozato, et al.  \"Radiat Res.\"  190, \"Chromosomal abnormalities in human lymphocytes after computed tomography scan procedure.\" 424 (2018)","DOI":"10.1667\/RR14976.1"},{"key":"26","doi-asserted-by":"crossref","unstructured":"H Sakane, M Ishida, L Shi, et al.  \"Radiology.\"  295, \"Biological effects of low-dose chest CT on chromosomal DNA.\" 439 (2020)","DOI":"10.1148\/radiol.2020190389"},{"key":"27","doi-asserted-by":"crossref","unstructured":"S Neubauer, J Dunst, E Gebhart,  \"Radiother Oncol.\"  43, \"The impact of complex chromosomal rearrangements on the detection of radiosensitivity in cancer patients.\" 189 (1997)","DOI":"10.1016\/S0167-8140(97)01932-4"},{"key":"28","doi-asserted-by":"crossref","unstructured":"K Baria, C Warren, SA Roberts, et al.  \"Br J Cancer.\"  84, \"Chromosomal radiosensitivity as a marker of predisposition to common cancers?\" 892 (2001)","DOI":"10.1054\/bjoc.2000.1701"},{"key":"29","doi-asserted-by":"crossref","unstructured":"U Keller, A Kuechler, T Liehr, et al.  \"Strahlenther Onkol.\"  180, \"Impact of various parameters in detecting chromosomal aberrations by FISH to describe radiosensitivity.\" 289 (2004)","DOI":"10.1007\/s00066-004-1200-y"},{"key":"30","doi-asserted-by":"crossref","unstructured":"ML Chua  and K Rothkamm  \"Clin Oncol (R Coll Radiol).\"  25, \"Biomarkers of radiation exposure: can they predict normal tissue radiosensitivity?\" 610 (2013)","DOI":"10.1016\/j.clon.2013.06.010"},{"key":"31","doi-asserted-by":"crossref","unstructured":"O Popanda, R Ebbeler, D Twardella, et al.  \"Int J Radiat Oncol Biol Phys.\"  55, \"Radiation-induced DNA damage and repair in lymphocytes from breast cancer patients and their correlation with acute skin reactions to radiotherapy.\" 1216 (2003)","DOI":"10.1016\/S0360-3016(02)04415-2"},{"key":"33","unstructured":"K Rothkamm  and S Horn  \"Ann Ist Super Sanita.\"  45, \"Gamma-H2AX as protein biomarker for radiation exposure.\" 265 (2009)"},{"key":"35","doi-asserted-by":"crossref","unstructured":"Q Wen, Y Hu, F Ji, et al.  \"Radiat Oncol.\"  6, \"Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy.\" 133 (2011)","DOI":"10.1186\/1748-717X-6-133"},{"key":"39","doi-asserted-by":"crossref","unstructured":"E Pariset, A Bertucci, M Petay, et al.  \"Cell Rep.\"  21, \"DNA damage baseline predicts resilience to space radiation and radiotherapy.\" 108434 (2020)","DOI":"10.1016\/j.celrep.2020.108434"},{"key":"40","doi-asserted-by":"crossref","unstructured":"C Hartel, E Nasonova, MC Fuss, et al.  \"Clin Transl Radiat Oncol.\"  13, \"Persistence of radiation-induced aberrations in patients after radiotherapy with C-ions and IMRT.\" 57 (2018)","DOI":"10.1016\/j.ctro.2018.10.002"},{"key":"41","doi-asserted-by":"crossref","unstructured":"A Diener, G Stephan, T Vogl, et al.  \"Radiat Res.\"  114, \"The induction of chromosome aberrations during the course of radiation therapy for morbus Hodgkin.\" 528 (1988)","DOI":"10.2307\/3577123"},{"key":"42","doi-asserted-by":"crossref","unstructured":"A Matsuoka, K Yamada, M Hayashi, et al.  \"J Radiat Res.\"  37, \"Chromosomal aberrations detected by chromosome painting in lymphocytes from cancer patients given high doses of therapeutic X-rays.\" 257 (1996)","DOI":"10.1269\/jrr.37.257"},{"key":"44","doi-asserted-by":"crossref","unstructured":"B Sreedevi, BS Rao, H Nagaraj, et al.  \"Radiat Prot Dosimetry.\"  94, \"Chromosome aberration analysis in radiotherapy patients and simulated partial body exposures: biological dosimetry for non-uniform exposures.\" 317 (2001)","DOI":"10.1093\/oxfordjournals.rpd.a006505"},{"key":"45","doi-asserted-by":"crossref","unstructured":"S Roch-Lefevre, F Pouzoulet, AL Giraudet, et al.  \"Br J Radiol.\"  83, \"Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy.\" 759 (2010)","DOI":"10.1259\/bjr\/210225597"},{"key":"46","doi-asserted-by":"crossref","unstructured":"A Aurias, B Dutrillaux, D Buriot, et al.  \"Mutat Res.\"  69, \"High frequencies of inversions and translocations of chromosomes 7 and 14 in ataxia telangiectasia.\" 369 (1980)","DOI":"10.1016\/0027-5107(80)90101-3"},{"key":"47","doi-asserted-by":"crossref","unstructured":"D Scott, AR Spreadborough, LA Jones, et al.  \"Radiat Res.\"  145, \"Chromosomal radiosensitivity in G2-phase lymphocytes as an indicator of cancer predisposition.\" 3 (1996)","DOI":"10.2307\/3579189"},{"key":"48","doi-asserted-by":"crossref","unstructured":"A Baeyens, H Thierens, K Claes, et al.  \"Br J Cancer.\"  87, \"Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition.\" 1379 (2002)","DOI":"10.1038\/sj.bjc.6600628"},{"key":"49","doi-asserted-by":"crossref","unstructured":"LV Distel, S Neubauer, U Keller, et al.  \"Radiother Oncol.\"  81, \"Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients.\" 257 (2006)","DOI":"10.1016\/j.radonc.2006.10.012"},{"key":"50","doi-asserted-by":"crossref","unstructured":"X Yin, J Mason, PN Lobachevsky, et al.  \"Int J Radiat Oncol Biol Phys.\"  103, \"Radiation therapy modulates DNA repair efficiency in peripheral blood mononuclear cells of patients with non-small cell lung cancer.\" 521 (2019)","DOI":"10.1016\/j.ijrobp.2018.10.001"},{"key":"36","doi-asserted-by":"crossref","unstructured":"K Rothkamm, C Beinke, H Romm, et al.  \"Radiat Res.\"  180, \"Comparison of established and emerging biodosimetry assays.\" 111 (2013)","DOI":"10.1667\/RR3231.1"},{"key":"37","doi-asserted-by":"crossref","unstructured":"LA Beaton, C Ferrarotto, L Marro, et al.  \"Int J Radiat Oncol Biol Phys.\"  85, \"Chromosome damage and cell proliferation rates in in vitro irradiated whole blood as markers of late radiation toxicity after radiation therapy to the prostate.\" 1346 (2013)","DOI":"10.1016\/j.ijrobp.2012.09.026"},{"key":"22","doi-asserted-by":"crossref","unstructured":"S Siva, P Lobachevsky, MP MacManus, et al.  \"Clin Cancer Res.\"  22, \"Radiotherapy for non-small cell lung cancer induces DNA damage response in both irradiated and out-of-field normal tissues.\" 4817 (2016)","DOI":"10.1158\/1078-0432.CCR-16-0138"},{"key":"17","doi-asserted-by":"crossref","unstructured":"TT Paull, EP Rogakou, V Yamazaki, et al.  \"Curr Biol.\"  10, \"A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage.\" 886 (2000)","DOI":"10.1016\/S0960-9822(00)00610-2"},{"key":"43","doi-asserted-by":"crossref","unstructured":"A Tichy, S Kabacik, G O'Brien, et al.  \"PLOS One.\"  13, \"The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood.\" e0193412 (2018)","DOI":"10.1371\/journal.pone.0193412"},{"key":"32","doi-asserted-by":"crossref","unstructured":"M Durante  and SC Formenti  \"Front Oncol.\"  8, \"Radiation-induced chromosomal aberrations and immunotherapy: Micronuclei, cytosolic DNA, and interferon-production pathway.\" 192 (2018)","DOI":"10.3389\/fonc.2018.00192"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T09:58:21Z","timestamp":1793440701000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-195\/issue-3\/RADE-20-00234.1\/Evaluating-Individual-Radiosensitivity-for-the-Prediction-of-Acute-Toxicities-of\/10.1667\/RADE-20-00234.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,30]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-20-00234.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,30]]}}}