{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:46:35Z","timestamp":1787240795918,"version":"build-2736575974"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Investissements d\u2019avenir","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]},{"name":"SiRIC CURAMUS","award":["INCa-DGOS-Inserm_12560"],"award-info":[{"award-number":["INCa-DGOS-Inserm_12560"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival\u2009&gt;\u200930\u00a0months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2\/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M\/31F) were included in the study. The median age at the time of radiotherapy was 48\u00a0years old (range 18\u201369). The median follow-up after the completion of radiotherapy was 79\u00a0months. A total of 44 patients (44\/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n\u2009=\u200928), gait disturbances (n\u2009=\u200912), and urinary incontinence (n\u2009=\u20099). The cumulative incidence of RIL was 21% at 12\u00a0months, 42% at 36\u00a0months, and 48% at 60\u00a0months. Age\u2009&gt;\u200960\u00a0years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.<\/jats:p>","DOI":"10.1038\/s41598-021-89216-1","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T06:03:16Z","timestamp":1620885796000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors"],"prefix":"10.1038","volume":"11","author":[{"given":"Robert","family":"Terziev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Psimaras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Marie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loic","family":"Feuvret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Berzero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dehais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavie","family":"Bompaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Kinnersley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Delattre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Idbaih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khe","family":"Hoang-Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Sanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Ricard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"89216_CR1","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1016\/S0140-6736(11)61346-9","volume":"379","author":"D Ricard","year":"2012","unstructured":"Ricard, D. et al. Primary brain tumours in adults. Lancet (London, England) 379, 1984\u20131996 (2012).","journal-title":"Lancet (London, England)"},{"key":"89216_CR2","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1016\/S0140-6736(09)61299-X","volume":"374","author":"C Soussain","year":"2009","unstructured":"Soussain, C. et al. CNS complications of radiotherapy and chemotherapy. Lancet (London, England) 374, 1639\u20131651 (2009).","journal-title":"Lancet (London, England)"},{"key":"89216_CR3","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-018-4296-9","author":"F Bompaire","year":"2018","unstructured":"Bompaire, F. et al. New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study. Supp. Care Cancer https:\/\/doi.org\/10.1007\/s00520-018-4296-9 (2018).","journal-title":"Supp. Care Cancer"},{"key":"89216_CR4","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1001\/archneur.62.10.1595","volume":"62","author":"AMP Omuro","year":"2005","unstructured":"Omuro, A. M. P. et al. Delayed neurotoxicity in primary central nervous system lymphoma. Arch. Neurol. 62, 1595\u20131600 (2005).","journal-title":"Arch. Neurol."},{"key":"89216_CR5","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1212\/WNL.0000000000000617","volume":"83","author":"DD Correa","year":"2014","unstructured":"Correa, D. D. et al. APOE polymorphisms and cognitive functions in patients with brain tumors. Neurology 83, 320\u2013327 (2014).","journal-title":"Neurology"},{"key":"89216_CR6","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1016\/S1470-2045(15)00380-0","volume":"17","author":"JS Wefel","year":"2016","unstructured":"Wefel, J. S., Noll, K. R. & Scheurer, M. E. Neurocognitive functioning and genetic variation in patients with primary brain tumours. Lancet Oncol. 17, e97\u2013e108 (2016).","journal-title":"Lancet Oncol."},{"key":"89216_CR7","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1200\/JCO.2009.26.3541","volume":"28","author":"PY Wen","year":"2018","unstructured":"Wen, P. Y., Macdonald, D. R., Reardon, D. A., Cloughesy, T. F. & Sorensen, A. G. Updated response assessment criteria for high-grade gliomas: response assessment in Neuro-Oncology Working Group. J. Clin. Oncol. 28, 1963\u20131972 (2018).","journal-title":"J. Clin. Oncol."},{"key":"89216_CR8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/0022-510X(93)90041-V","volume":"114","author":"P Scheltens","year":"1993","unstructured":"Scheltens, P. et al. A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J. Neurol. Sci. 114, 7\u201312 (1993).","journal-title":"J. Neurol. Sci."},{"key":"89216_CR9","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1093\/hmg\/ddr192","volume":"20","author":"M Sanson","year":"2011","unstructured":"Sanson, M. et al. Chromosome 7p11.2 (EGFR) variation influences glioma risk. Hum. Mol. Genet. 20, 2897\u20132904 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"89216_CR10","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1016\/j.oraloncology.2012.08.002","volume":"48","author":"N Ghazali","year":"2012","unstructured":"Ghazali, N., Shaw, R. J., Rogers, S. N. & Risk, J. M. Genomic determinants of normal tissue toxicity after radiotherapy for head and neck malignancy: a systematic review. Oral Oncol. 48, 1090\u20131100 (2012).","journal-title":"Oral Oncol."},{"key":"89216_CR11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/S0167-8140(02)00154-8","volume":"64","author":"CN Andreassen","year":"2002","unstructured":"Andreassen, C. N., Alsner, J. & Overgaard, J. Does variability in normal tissue reactions after radiotherapy have a genetic basis\u2014where and how to look for it? Radiother. Oncol. 64, 131\u2013140 (2002).","journal-title":"Radiother. Oncol."},{"key":"89216_CR12","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.semradonc.2010.05.003","volume":"20","author":"MB Parliament","year":"2010","unstructured":"Parliament, M. B. & Murray, D. Single nucleotide polymorphisms of DNA repair genes as predictors of radioresponse. Semin. Radiat. Oncol. 20, 232\u2013240 (2010).","journal-title":"Semin. Radiat. Oncol."},{"key":"89216_CR13","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.radonc.2003.09.010","volume":"69","author":"CN Andreassen","year":"2003","unstructured":"Andreassen, C. N., Alsner, J., Overgaard, M. & Overgaard, J. Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes. Radiother. Oncol. 69, 127\u2013135 (2003).","journal-title":"Radiother. Oncol."},{"key":"89216_CR14","doi-asserted-by":"publisher","first-page":"7063","DOI":"10.1158\/1078-0432.CCR-06-0039","volume":"12","author":"J Ahn","year":"2006","unstructured":"Ahn, J. et al. Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer. Clin. Cancer Res. 12, 7063\u20137070 (2006).","journal-title":"Clin. Cancer Res."},{"key":"89216_CR15","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1748-717X-8-125","volume":"8","author":"G Alsbeih","year":"2013","unstructured":"Alsbeih, G. et al. SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers. Radiat. Oncol. 8, 125 (2013).","journal-title":"Radiat. Oncol."},{"key":"89216_CR16","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1080\/01621459.1999.10474144","volume":"94","author":"JP Fine","year":"1999","unstructured":"Fine, J. P. & R. J. G. ,. A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 94, 496\u2013509 (1999).","journal-title":"J. Am. Stat. Assoc."},{"key":"89216_CR17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. B"},{"key":"89216_CR18","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1212\/01.WNL.0000109673.75316.D8","volume":"62","author":"DD Correa","year":"2004","unstructured":"Correa, D. D. et al. Cognitive functions in survivors of primary central nervous system lymphoma. Neurology 62, 548\u2013555 (2004).","journal-title":"Neurology"},{"key":"89216_CR19","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1200\/JCO.1998.16.3.864","volume":"16","author":"JY Blay","year":"1998","unstructured":"Blay, J. Y. et al. High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series. J. Clin. Oncol. 16, 864\u2013871 (1998).","journal-title":"J. Clin. Oncol."},{"key":"89216_CR20","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1023\/A:1010676807228","volume":"52","author":"MW Wassenberg","year":"2001","unstructured":"Wassenberg, M. W., Bromberg, J. E., Witkamp, T. D., Terhaard, C. H. & Taphoorn, M. J. White matter lesions and encephalopathy in patients treated for primary central nervous system lymphoma. J. Neurooncol. 52, 73\u201380 (2001).","journal-title":"J. Neurooncol."},{"key":"89216_CR21","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s11060-013-1310-4","volume":"116","author":"FE Froklage","year":"2014","unstructured":"Froklage, F. E. et al. Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma: a prospective longitudinal study. J. Neurooncol. 116, 387\u2013394 (2014).","journal-title":"J. Neurooncol."},{"key":"89216_CR22","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1001\/archneur.1993.00540080076020","volume":"50","author":"JL Cummings","year":"1993","unstructured":"Cummings, J. L. Frontal-subcortical circuits and human behavior. Arch. Neurol. 50, 873\u2013880 (1993).","journal-title":"Arch. Neurol."},{"key":"89216_CR23","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1212\/01.WNL.0000130530.55104.B5","volume":"63","author":"M Tullberg","year":"2004","unstructured":"Tullberg, M. et al. White matter lesions impair frontal lobe function regardless of their location. Neurology 63, 246\u2013253 (2004).","journal-title":"Neurology"},{"key":"89216_CR24","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/S1474-4422(02)00190-4","volume":"1","author":"GC Rom\u00e1n","year":"2002","unstructured":"Rom\u00e1n, G. C., Erkinjuntti, T., Wallin, A., Pantoni, L. & Chui, H. C. Subcortical ischaemic vascular dementia. Lancet. Neurol. 1, 426\u2013436 (2002).","journal-title":"Lancet. Neurol."},{"key":"89216_CR25","first-page":"1166","volume":"49","author":"AO Hebb","year":"2001","unstructured":"Hebb, A. O. & Cusimano, M. D. Idiopathic normal pressure hydrocephalus: a systematic review of diagnosis and outcome. Neurosurgery 49, 1166\u20131184 (2001) (discussion 1184-6).","journal-title":"Neurosurgery"},{"key":"89216_CR26","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3389\/fneur.2017.00286","volume":"8","author":"R Kassubek","year":"2017","unstructured":"Kassubek, R. et al. Cerebral microstructural alterations after radiation therapy in high-grade glioma: a diffusion tensor imaging-based study. Front. Neurol. 8, 286 (2017).","journal-title":"Front. Neurol."},{"key":"89216_CR27","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1016\/j.neurol.2011.07.005","volume":"167","author":"JR Fike","year":"2011","unstructured":"Fike, J. R. Physiopathology of radiation-induced neurotoxicity. Rev. Neurol. (Paris) 167, 746\u2013750 (2011).","journal-title":"Rev. Neurol. (Paris)"},{"key":"89216_CR28","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1212\/01.WNL.0000106941.51340.A2","volume":"62","author":"R Lai","year":"2004","unstructured":"Lai, R., Abrey, L. E., Rosenblum, M. K. & DeAngelis, L. M. Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study. Neurology 62, 451\u2013456 (2004).","journal-title":"Neurology"},{"key":"89216_CR29","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1667\/0033-7587(2000)153[0357:TROTCN]2.0.CO;2","volume":"153","author":"PJ Tofilon","year":"2000","unstructured":"Tofilon, P. J. & Fike, J. R. The radioresponse of the central nervous system: a dynamic process. Radiat. Res. 153, 357\u2013370 (2000).","journal-title":"Radiat. Res."},{"key":"89216_CR30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fnins.2014.00145","volume":"8","author":"B El Waly","year":"2014","unstructured":"El Waly, B., Macchi, M., Cayre, M. & Durbec, P. Oligodendrogenesis in the normal and pathological central nervous system. Front. Neurosci. 8, 145 (2014).","journal-title":"Front. Neurosci."},{"key":"89216_CR31","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1161\/01.ATV.0000069210.46539.0D","volume":"23","author":"KM Hannan","year":"2003","unstructured":"Hannan, K. M., Dilley, R. J., de Dios, S. T. & Little, P. J. Troglitazone stimulates repair of the endothelium and inhibits neointimal formation in denuded rat aorta. Arterioscler. Thromb. Vasc. Biol. 23, 762\u2013768 (2003).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"89216_CR32","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1161\/01.ATV.0000044461.01844.C9","volume":"23","author":"DS Calnek","year":"2003","unstructured":"Calnek, D. S., Mazzella, L., Roser, S., Roman, J. & Hart, C. M. Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler. Thromb. Vasc. Biol. 23, 52\u201357 (2003).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"89216_CR33","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1097\/HJH.0b013e32834f043b","volume":"30","author":"A Mart\u00edn","year":"2012","unstructured":"Mart\u00edn, A. et al. Peroxisome proliferator-activated receptor-\u03b3 activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress. J. Hypertens. 30, 315\u2013326 (2012).","journal-title":"J. Hypertens."},{"key":"89216_CR34","doi-asserted-by":"publisher","first-page":"e00129","DOI":"10.1042\/AN20130030","volume":"5","author":"S Mandrekar-Colucci","year":"2013","unstructured":"Mandrekar-Colucci, S., Sauerbeck, A., Popovich, P. G. & McTigue, D. M. PPAR agonists as therapeutics for CNS trauma and neurological diseases. ASN Neuro 5, e00129 (2013).","journal-title":"ASN Neuro"},{"key":"89216_CR35","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1097\/NEN.0b013e3181aba2c1","volume":"68","author":"A Bernardo","year":"2009","unstructured":"Bernardo, A., Bianchi, D., Magnaghi, V. & Minghetti, L. Peroxisome proliferator-activated receptor-gamma agonists promote differentiation and antioxidant defenses of oligodendrocyte progenitor cells. J. Neuropathol. Exp. Neurol. 68, 797\u2013808 (2009).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"89216_CR36","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1097\/NEN.0b013e3182309ab1","volume":"70","author":"C De Nuccio","year":"2011","unstructured":"De Nuccio, C. et al. Peroxisome proliferator-activated receptor \u03b3 agonists accelerate oligodendrocyte maturation and influence mitochondrial functions and oscillatory Ca(2+) waves. J. Neuropathol. Exp. Neurol. 70, 900\u2013912 (2011).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"89216_CR37","doi-asserted-by":"publisher","first-page":"e50500","DOI":"10.1371\/journal.pone.0050500","volume":"7","author":"S Kanakasabai","year":"2012","unstructured":"Kanakasabai, S. et al. PPAR\u03b3 agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes. PLoS ONE 7, e50500 (2012).","journal-title":"PLoS ONE"},{"key":"89216_CR38","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1667\/RR13202.1","volume":"181","author":"D Greene-Schloesser","year":"2014","unstructured":"Greene-Schloesser, D. et al. The peroxisomal proliferator-activated receptor (PPAR) \u03b1 agonist, fenofibrate, prevents fractionated whole-brain irradiation-induced cognitive impairment. Radiat. Res. 181, 33\u201344 (2014).","journal-title":"Radiat. Res."},{"key":"89216_CR39","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.lungcan.2015.11.005","volume":"90","author":"M Mangoni","year":"2015","unstructured":"Mangoni, M. et al. A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model. Lung Cancer 90, 405\u2013409 (2015).","journal-title":"Lung Cancer"},{"key":"89216_CR40","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1111\/fcp.12119","volume":"29","author":"IT Abdel-Raheem","year":"2015","unstructured":"Abdel-Raheem, I. T., Omran, G. A. & Katary, M. A. Irbesartan, an angiotensin II receptor antagonist, with selective PPAR-gamma-modulating activity improves function and structure of chemotherapy-damaged ovaries in rats. Fundam. Clin. Pharmacol. 29, 286\u2013298 (2015).","journal-title":"Fundam. Clin. Pharmacol."},{"key":"89216_CR41","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ijrobp.2006.09.036","volume":"67","author":"W Zhao","year":"2007","unstructured":"Zhao, W. et al. Administration of the peroxisomal proliferator-activated receptor \u03b3 agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment. Int. J. Radiat. Oncol. Biol. Phys. 67, 6\u20139 (2007).","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"89216_CR42","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.ijrobp.2009.06.059","volume":"75","author":"S Ramanan","year":"2009","unstructured":"Ramanan, S. et al. The PPARalpha agonist fenofibrate preserves hippocampal neurogenesis and inhibits microglial activation after whole-brain irradiation. Int. J. Radiat. Oncol. Biol. Phys. 75, 870\u2013877 (2009).","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"89216_CR43","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.intimp.2016.12.003","volume":"43","author":"Z Zhang","year":"2017","unstructured":"Zhang, Z. et al. PPAR\u03b3 activation ameliorates postoperative cognitive decline probably through suppressing hippocampal neuroinflammation in aged mice. Int. Immunopharmacol. 43, 53\u201361 (2017).","journal-title":"Int. Immunopharmacol."},{"key":"89216_CR44","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s00432-018-2791-5","volume":"145","author":"CK Cramer","year":"2019","unstructured":"Cramer, C. K. et al. Safety of pioglitazone during and after radiation therapy in patients with brain tumors: a phase I clinical trial. J. Cancer Res. Clin. Oncol. 145, 337\u2013344 (2019).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"89216_CR45","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1080\/08037050600771583","volume":"15","author":"A Zanchetti","year":"2006","unstructured":"Zanchetti, A. & Elmfeldt, D. Findings and implications of the Study on COgnition and Prognosis in the Elderly (SCOPE)\u2014a review. Blood Press. 15, 71\u201379 (2006).","journal-title":"Blood Press."},{"key":"89216_CR46","first-page":"CD013047","volume":"2019","author":"TA Lawrie","year":"2019","unstructured":"Lawrie, T. A. et al. Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma. Cochrane Database Syst. Rev. 2019, CD013047 (2019).","journal-title":"Cochrane Database Syst. Rev."},{"key":"89216_CR47","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa252","author":"M Klein","year":"2020","unstructured":"Klein, M. et al. Memory in low-grade glioma patients treated with radiotherapy or temozolomide: a correlative analysis of EORTC study 22033\u201326033. Neuro Oncol. https:\/\/doi.org\/10.1093\/neuonc\/noaa252 (2020).","journal-title":"Neuro Oncol."},{"key":"89216_CR48","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1016\/S0140-6736(17)31442-3","volume":"390","author":"MJ van den Bent","year":"2017","unstructured":"van den Bent, M. J. et al. Interim results from the CATNON trial (EORTC study 26053\u201322054) of treatment with concurrent and adjuvant temozolomide for 1p\/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet 390, 1645\u20131653 (2017).","journal-title":"Lancet"},{"key":"89216_CR49","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.neurol.2011.08.005","volume":"167","author":"D Ricard","year":"2011","unstructured":"Ricard, D., Soussain, C. & Psimaras, D. Neurotoxicity of the CNS: diagnosis, treatment and prevention. Rev. Neurol. (Paris) 167, 737\u2013745 (2011).","journal-title":"Rev. Neurol. (Paris)"},{"key":"89216_CR50","unstructured":"Study of Neurological Complication After Radiotherapy for High Grade Glioblastoma\u2014Full Text View\u2014ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02544178."},{"key":"89216_CR51","unstructured":"Cognitive Function After Treatment of Primary CNS Malignancy\u2014Full Text View\u2014ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03055364."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89216-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89216-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89216-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T16:25:16Z","timestamp":1725035116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89216-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,13]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["89216"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-89216-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,13]]},"assertion":[{"value":"26 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10176"}}