{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:19:08Z","timestamp":1791231548990,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007059","name":"Northwestern University","doi-asserted-by":"publisher","award":["P50CA221747"],"award-info":[{"award-number":["P50CA221747"]}],"id":[{"id":"10.13039\/100007059","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole-brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus has been demonstrated, global structural shape changes after WBRT remain to be studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We studied healthy controls and patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a validated graph convolutional neural network model to estimate patient\u2019s \u201cbrain age\u201d. We further developed a mixed-effects linear model to compare the estimated age of the whole brain and substructures before and after WBRT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>4220 subjects were analyzed (4148 healthy controls and 72 patients). The median radiation dose was 30 Gy (range 25\u201337.5 Gy). The whole brain and substructures underwent structural change resembling rapid aging in radiated patients compared to healthy controls; the whole brain \u201caged\u201d 9.32 times faster, the cortex 8.05 times faster, the subcortical structures 12.57 times faster, and the hippocampus 10.14 times faster. In a subset analysis, the hippocampus \u201caged\u201d 8.88 times faster in patients after conventional WBRT versus after hippocampal avoidance (HA)-WBRT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings suggest that WBRT causes the brain and its substructures to undergo structural changes at a pace up to 13x of the normal aging pace, where hippocampal avoidance offers focal structural protection. Correlating these structural imaging changes with neurocognitive outcomes following WBRT or HA-WBRT would benefit from future analysis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noad029","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T09:40:42Z","timestamp":1675417242000},"page":"1323-1330","source":"Crossref","is-referenced-by-count":16,"title":["Whole-brain radiotherapy associated with structural changes resembling aging as determined by anatomic surface-based deep learning"],"prefix":"10.1093","volume":"25","author":[{"given":"Nikhil","family":"Rammohan","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Northwestern University Feinberg School of Medicine , Chicago, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Northwestern University Feinberg School of Medicine , Chicago, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0591-7542","authenticated-orcid":false,"given":"Pierre","family":"Besson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Northwestern University Feinberg School of Medicine , Chicago, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim J","family":"Kruser","sequence":"additional","affiliation":[{"name":"SSM Health Dean Medical Group, Turville Bay Radiation Oncology Center , Madison, WI , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S Kathleen","family":"Bandt","sequence":"additional","affiliation":[{"name":"Department of Neurologic Surgery, Northwestern University Feinberg School of Medicine , Chicago, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"issue":"5","key":"2023070706474512400_CIT0001","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1200\/JCO.2017.75.9589","article-title":"Whole-brain radiotherapy for brain metastases: evolution or revolution?","volume":"36","author":"Brown","year":"2018","journal-title":"J Clin Oncol."},{"key":"2023070706474512400_CIT0002","doi-asserted-by":"crossref","first-page":"i6483","DOI":"10.1136\/bmj.i6483","article-title":"Whole brain radiotherapy for brain metastases","volume":"355","author":"Brown","year":"2016","journal-title":"BMJ"},{"issue":"8","key":"2023070706474512400_CIT0003","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1200\/JCO.2005.04.6185","article-title":"Whole-brain radiotherapy in the management of brain metastasis","volume":"24","author":"Khuntia","year":"2006","journal-title":"J Clin Oncol."},{"issue":"32","key":"2023070706474512400_CIT0004","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1200\/JCO.20.01255","article-title":"Survival in patients with brain metastases: summary report on the updated diagnosis-specific graded prognostic assessment and definition of the eligibility quotient","volume":"38","author":"Sperduto","year":"2020","journal-title":"J Clin Oncol."},{"issue":"8","key":"2023070706474512400_CIT0005","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/S1470-2045(17)30441-2","article-title":"Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C\/CEC.3): a multicentre, randomised, controlled, phase 3 trial","volume":"18","author":"Brown","year":"2017","journal-title":"Lancet Oncol."},{"issue":"4","key":"2023070706474512400_CIT0006","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1001\/jama.2016.9839","article-title":"Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial","volume":"316","author":"Brown","year":"2016","journal-title":"JAMA."},{"issue":"4","key":"2023070706474512400_CIT0007","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1001\/jamaoncol.2015.1145","article-title":"Stereotactic Radiosurgery With or Without Whole-Brain Radiotherapy for Brain Metastases: Secondary Analysis of the JROSG 99-1 Randomized Clinical Trial","volume":"1","author":"Aoyama","year":"2015","journal-title":"JAMA Oncol"},{"issue":"4","key":"2023070706474512400_CIT0008","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ijrobp.2013.02.033","article-title":"Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: pooled secondary analysis of Radiation Therapy Oncology Group randomized trials 0212 and 0214","volume":"86","author":"Gondi","year":"2013","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"3","key":"2023070706474512400_CIT0009","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.radonc.2010.09.013","article-title":"Why avoid the hippocampus? 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