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We evaluated brain metabolic correlates of CRS with and without ICANS in diffuse large B\u2010cell lymphoma patients treated with CAR\u2010T.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010one refractory DLCBLs underwent whole\u2010body and brain [<jats:sup>18<\/jats:sup>F]\u2010fluorodeoxyglucose (FDG) PET before and 30\u00a0days after treatment with CAR\u2010T. Five patients did not develop inflammatory\u2010related side effects, 11 patients developed CRS, while in 5 patients CRS evolved in ICANS. Baseline and post\u2010CAR\u2010T brain FDG\u2010PET were compared with a local controls dataset to identify hypometabolic patterns both at single\u2010patient and group levels (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05 after correction for family\u2010wise error [FWE). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were computed on baseline FDG\u2010PET and compared between patients\u2019 subgroups (<jats:italic>t<\/jats:italic>\u2010test).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ICANS showed an extended and bilateral hypometabolic pattern mainly involving the orbitofrontal cortex, frontal dorsolateral cortex, and anterior cingulate (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.003 FWE\u2010corrected). CRS without ICANS showed significant hypometabolism in less extended clusters mainly involving bilateral medial and lateral temporal lobes, posterior parietal lobes, anterior cingulate, and cerebellum (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.002 FWE\u2010corrected). When compared, ICANS showed a more prominent hypometabolism in the orbitofrontal and frontal dorsolateral cortex in both hemispheres than CRS (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.002 FWE\u2010corrected). Mean baseline MTV and TLG were significantly higher in ICANS than CRS (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with ICANS are characterized by a frontolateral hypometabolic signature coherently with the hypothesis of ICANS as a predominant frontal syndrome and with the more prominent susceptibility of frontal lobes to cytokine\u2010induced inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jon.13135","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T03:10:24Z","timestamp":1686280224000},"page":"825-836","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Brain FDG\u2010PET findings in chimeric antigen receptor T\u2010cell therapy neurotoxicity for diffuse large B\u2010cell lymphoma"],"prefix":"10.1111","volume":"33","author":[{"given":"Silvia","family":"Morbelli","sequence":"first","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino  Genova Italy"},{"name":"Nuclear Medicine Unit, Department of Health Sciences (DISSAL) University of Genoa  Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"Gambella","sequence":"additional","affiliation":[{"name":"Department of Hematology and Cellular Therapy IRCCS Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Raiola","sequence":"additional","affiliation":[{"name":"Department of Hematology and Cellular Therapy IRCCS Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Ghiggi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Cellular Therapy IRCCS Ospedale Policlinico San 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