{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:23:22Z","timestamp":1769070202984,"version":"3.49.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Chemotherapy-related brain impairments and changes can occur in patients with lung cancer after platinum chemotherapy and have a substantial impact on survivors\u2019 quality of life. Therefore, it is necessary to understand the brain neuropathological alterations and response mechanisms to provide a theoretical basis for rehabilitation strategies. This study aimed to investigate the related brain morphological changes and clarified their correlation with clinical and pathological indicators in patients with lung cancer after platinum chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Overall, 28 patients with chemotherapy, 56 patients without chemotherapy, and 41 healthy controls were categorized in three groups, matched for age, sex, and years of education, and included in the cross-sectional comparison of brain volume and cortical thickness. 14 matched patients before and after chemotherapy were subjected to paired comparison for longitudinal observation of brain morphological changes. Three-dimensional T<jats:sub>1<\/jats:sub>-weighted images were acquired from all participants, and quantitative parameters were calculated using the formula of the change from baseline. Correlation analysis was performed to evaluate the relationship between abnormal morphological indices and clinical information of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Brain regions with volume differences among the three groups were mainly distributed in frontal lobe and limbic cortex. Additionally, significant differences in cerebrospinal fluid were observed in most ventricles, and the main brain regions with cortical thickness differences were the gyrus rectus and medial frontal cortex of the frontal lobe, transverse temporal gyrus of the temporal lobe, insular cortex, anterior insula, and posterior insula of the insular cortex. According to the paired comparison, decreased brain volumes in the patients after chemotherapy appeared in some regions of the frontal, parietal, temporal, and occipital lobes; limbic cortex; insular cortex; and lobules VI-X and decreased cortical thickness in the patients after chemotherapy was found in the frontal, temporal, limbic, and insular cortexes. In the correlation analysis, only the differentiation degree of the tumor and duration after chemotherapy were significantly correlated with imaging indices in the abnormal brain regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings illustrate the platinum-related brain reactivity morphological alterations which provide more insights into the neuropathological mechanisms of patients with lung cancer after platinum chemotherapy and empirical support for the details of brain injury related to cancer and chemotherapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2022.903249","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T06:46:46Z","timestamp":1659595606000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Brain morphological alterations and their correlation to tumor differentiation and duration in patients with lung cancer after platinum chemotherapy"],"prefix":"10.3389","volume":"12","author":[{"given":"Pin","family":"Lv","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guolin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Xin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaming","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ShangWen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Rong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningyu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowei","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"pkz099","DOI":"10.1093\/jncics\/pkz099","article-title":"Identifying cancer-related cognitive impairment using the FACT-cog perceived cognitive impairment","volume":"4","author":"Dyk","year":"2020","journal-title":"JNCI Cancer Spectrum"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/pon.4190","article-title":"Objective-subjective disparity in cancer-related cognitive impairment: does the use of change measures help reconcile the difference","volume":"26","author":"O'Farrell","year":"2017","journal-title":"Psycho-Oncology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/13803395.2013.781995","article-title":"Study of the cognitive effects of chemotherapy: Considerations in selection of a control group","volume":"35","author":"Collins","year":"2013","journal-title":"J Clin Exp Neuropsyc"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-019-05095-3","article-title":"The impact of chemotherapy on cognitive function: A multicentre prospective cohort study in testicular cancer","volume":"28","author":"Whitford","year":"2020","journal-title":"Support Care Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12885-019-5349-2","article-title":"Immediate-term cognitive impairment following intravenous (IV) chemotherapy: a prospective pre-post design study","volume":"19","author":"Khan","year":"2019","journal-title":"BMC Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/pon.4389","article-title":"Testing a novel account of the dissociation between self-reported memory problems and memory performance in chemotherapy-treated breast cancer survivors","volume":"27","author":"Paquet","year":"2018","journal-title":"Psycho-oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/pon.4635","article-title":"Distinct and heterogeneous trajectories of self-perceived cognitive impairment among Asian breast cancer survivors","volume":"27","author":"Ng","year":"2018","journal-title":"Psycho-Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.923567","article-title":"Catechol-O-Methyltransferase gene polymorphisms and the risk of chemotherapy-induced prospective memory impairment in breast cancer patients with varying tumor hormonal receptor expression","volume":"26","author":"Li","year":"2020","journal-title":"Med Sci Monitor"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1177\/1099800419887230","article-title":"Exploring relationships among peripheral amyloid beta, tau, cytokines, cognitive function, and psychosomatic symptoms in breast cancer survivors","volume":"22","author":"Henneghan","year":"2020","journal-title":"Biol Res Nurs"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2259","article-title":"Prechemotherapy levels of plasma dehydroepiandrosterone and its sulfated form as predictors of cancer-related cognitive impairment in patients with breast cancer receiving chemotherapy","volume":"39","author":"Toh","year":"2019","journal-title":"Pharmacother"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-020-00319-1","article-title":"Measuring decline in white matter integrity after systemic treatment for breast cancer: omitting skeletonization enhances sensitivity","volume":"15","author":"Mzayek","year":"2021","journal-title":"Brain Imaging Behav"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24082","article-title":"Advanced MR diffusion imaging and chemotherapy-related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma","volume":"39","author":"Sleurs","year":"2018","journal-title":"Hum Brain Mapp"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e4296","DOI":"10.1002\/nbm.4296","article-title":"Neural correlates of working memory function in pediatric cancer survivors treated with chemotherapy: An fMRI study","volume":"33","author":"Stefancin","year":"2020","journal-title":"Nmr Biomed"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-018-0030-y","article-title":"Chemotherapy-induced functional changes of the default mode network in patients with lung cancer","volume":"14","author":"Zhang","year":"2020","journal-title":"Brain Imaging Behav"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1089\/brain.2017.0574","article-title":"Brain network connectivity and executive function in long-term survivors of childhood acute lymphoblastic leukemia","volume":"8","author":"Kesler","year":"2018","journal-title":"Brain Connect"},{"key":"B16","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1186\/s12885-017-3793-4","article-title":"Subjective cognitive impairment and brain structural networks in Chinese gynaecological cancer survivors compared with age-matched controls: a cross-sectional study","volume":"17","author":"Zeng","year":"2017","journal-title":"BMC Cancer"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29737","article-title":"Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition among cancer survivors postchemotherapy compared with healthy controls","volume":"122","author":"Wang","year":"2016","journal-title":"Cancer-Am Cancer Soc"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-019-00158-z","article-title":"Cortical brain age from pre-treatment to post-chemotherapy in patients with breast cancer","volume":"37","author":"Henneghan","year":"2020","journal-title":"Neurotox Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s10548-019-00746-4","article-title":"Predicting patient reported outcomes of cognitive function using connectome-based predictive modeling in breast cancer","volume":"33","author":"Henneghan","year":"2020","journal-title":"Brain topogr"},{"key":"B20","doi-asserted-by":"publisher","first-page":"djx085","DOI":"10.1093\/jnci\/djx085","article-title":"Changes in brain structural networks and cognitive functions in testicular cancer patients receiving cisplatin-based chemotherapy","volume":"109","author":"Amidi","year":"2017","journal-title":"JNCI: J Natl Cancer Inst"},{"key":"B21","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.nicl.2017.12.032","article-title":"Performance monitoring in lung cancer patients pre- and post-chemotherapy using fine-grained electrophysiological measures","volume":"18","author":"Sim\u00f3","year":"2018","journal-title":"NeuroImage: Clin"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2193-1801-3-444","article-title":"A prospective study of grey matter and cognitive function alterations in chemotherapy-treated breast cancer patients","volume":"3","author":"Lepage","year":"2014","journal-title":"SpringerPlus"},{"key":"B23","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s13058-018-0965-3","article-title":"Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: A brain magnetic resonance imaging pilot study","volume":"20","author":"Chen","year":"2018","journal-title":"Breast Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.05.017","article-title":"Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors","volume":"30","author":"Kesler","year":"2013","journal-title":"Brain Behavior Immun"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.03.004","article-title":"Subtle hippocampal deformities in breast cancer survivors with reduced episodic memory and self-reported cognitive concerns","volume":"14","author":"Apple","year":"2017","journal-title":"NeuroImage: Clin"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx285","article-title":"International cognition and cancer task force recommendations for neuroimaging methods in the study of cognitive impairment in non-CNS cancer patients","volume":"110","author":"Deprez","year":"2018","journal-title":"JNCI: J Natl Cancer Inst"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-007-0341-9","article-title":"A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer","volume":"16","author":"Mar Fan","year":"2008","journal-title":"Support Care cancer"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33186","article-title":"Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A 3-arm randomized trial","volume":"126","author":"Dos Santos","year":"2020","journal-title":"Cancer-Am Cancer Soc"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23743","article-title":"Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis","volume":"38","author":"Coup\u00e9","year":"2017","journal-title":"Hum Brain mapp"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-05898-7","article-title":"Language impairment among patients with different types of cancer. Comparison with healthy adults","volume":"184","author":"Megari","year":"2020","journal-title":"Breast Cancer Res Tr"},{"key":"B31","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1007\/s12282-020-01094-z","article-title":"Chemotherapy-related cognitive impairment in patients with breast cancer based on MRS and DTI analysis","volume":"27","author":"Tong","year":"2020","journal-title":"Breast Cancer-Tokyo"},{"key":"B32","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s11682-016-9665-8","article-title":"Recovery from chemotherapy-induced white matter changes in young breast cancer survivors","volume":"12","author":"Billiet","year":"2018","journal-title":"Brain Imaging Behav"},{"key":"B33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jneuroim.2017.10.005","article-title":"Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy","volume":"314","author":"Williams","year":"2018","journal-title":"J neuroimmunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1186\/s12885-017-3861-9","article-title":"Evaluation of plasma brain-derived neurotrophic factor levels and self-perceived cognitive impairment post-chemotherapy: A longitudinal study","volume":"17","author":"Ng","year":"2017","journal-title":"BMC Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-018-9991-0","article-title":"Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: Impact of education level","volume":"14","author":"Perrier","year":"2020","journal-title":"Brain Imaging Behav"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgo.2019.09.016","article-title":"Effects of chemotherapy on aging white matter microstructure: A longitudinal diffusion tensor imaging study","volume":"11","author":"Chen","year":"2020","journal-title":"J Geriatr Oncol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2967\/jnmt.118.212316","article-title":"Regional changes in brain 18F-FDG uptake after prophylactic cranial irradiation and chemotherapy in small cell lung cancer may reflect functional changes","volume":"46","author":"Eshghi","year":"2018","journal-title":"J Nucl Med technol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1001\/jamaoncol.2015.4333","article-title":"Neurotoxic effects of anthracycline- vs nonanthracycline-based chemotherapy on cognition in breast cancer survivors","volume":"2","author":"Kesler","year":"2016","journal-title":"JAMA Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1177\/1534735420938450","article-title":"Managing cancer and living meaningfully (CALM) intervention on chemotherapy-related cognitive impairment in breast cancer survivors","volume":"19","author":"Ding","year":"2020","journal-title":"Integr Cancer Ther"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(96)00300-0","article-title":"The cognitive effects of recombinant interleukin-2 (rIL-2) therapy: A controlled clinical trial using computerised assessments","volume":"32","author":"Walker","year":"1996","journal-title":"Eur J Cancer (1990)"},{"key":"B41","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jneuroim.2018.04.012","article-title":"Identifying cytokine predictors of cognitive functioning in breast cancer survivors up to 10 years post chemotherapy using machine learning","volume":"320","author":"Henneghan","year":"2018","journal-title":"J Neuroimmunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2017.00555","article-title":"Predicting long-term cognitive outcome following breast cancer with pre-treatment resting state fMRI and random forest machine learning","volume":"11","author":"Kesler","year":"2017","journal-title":"Front Hum Neurosci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"12697","DOI":"10.3390\/ijms222312697","article-title":"Chemotherapy-induced cognitive impairment and hippocampal neurogenesis: A review of physiological mechanisms and interventions","volume":"22","author":"Sekeres","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-021-05977-7","article-title":"Animal models of chemotherapy-induced cognitive decline in preclinical drug development","volume":"238","author":"John","year":"2021","journal-title":"Psychopharmacol (Berl)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0232548","article-title":"Connectome analysis of brain functional network alterations in breast cancer survivors with and without chemotherapy","volume":"15","author":"Chen","year":"2020","journal-title":"PloS One"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-019-05230-y","article-title":"Intrinsic brain activity changes associated with adjuvant chemotherapy in older women with breast cancer: A pilot longitudinal study","volume":"176","author":"Chen","year":"2019","journal-title":"Breast Cancer Res Tr"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s12149-019-01331-2","article-title":"Impaired brain dopamine transporter in chemobrain patients submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1","volume":"33","author":"Vitor","year":"2019","journal-title":"Ann Nucl Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1097\/JTO.0000000000000345","article-title":"Cognitive and brain structural changes in a lung cancer population","volume":"10","author":"Sim\u00f3","year":"2015","journal-title":"J Thorac Oncol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-020-05616-5","article-title":"Correlates of cognitive impairment in adult cancer survivors who have received chemotherapy and report cognitive problems","volume":"29","author":"Gutenkunst","year":"2021","journal-title":"Support Care Cancer"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/pon.4928","article-title":"Associations of functional, psychosocial, medical, and socio-demographic factors with cognitive screening in chemotherapy na\u00efve patients with breast cancer","volume":"28","author":"Nakamura","year":"2019","journal-title":"Psycho-oncol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.4040\/jkan.2019.49.4.375","article-title":"A structural model for chemotherapy related cognitive impairment and quality of life in breast cancer patients","volume":"49","author":"Lee","year":"2019","journal-title":"J korean Acad nurs"},{"key":"B52","doi-asserted-by":"publisher","first-page":"4994","DOI":"10.1002\/hbm.24753","article-title":"Age-dependent brain volume and neuropsychological changes after chemotherapy in breast cancer patients","volume":"40","author":"Blommaert","year":"2019","journal-title":"Hum Brain mapp"},{"key":"B53","doi-asserted-by":"publisher","first-page":"45135","DOI":"10.1038\/srep45135","article-title":"Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors","volume":"7","author":"Cheng","year":"2017","journal-title":"Sci rep-uk"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.903249\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T13:01:27Z","timestamp":1660050087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.903249\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,4]]},"references-count":53,"alternative-id":["10.3389\/fonc.2022.903249"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.903249","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,4]]},"article-number":"903249"}}