{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:21:05Z","timestamp":1790115665431,"version":"4.0.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T00:00:00Z","timestamp":1555545600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Survivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation\u2014including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning\u2014were identified. Multivariate analyses were performed to assess differences in neuropsychological outcomes and included tests for interaction between treatment cohort and follow-up time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between 1998 and 2017, 125 patients with tumors located in the supratentorial (17.6%), midline (28.8%), or posterior fossa (53.6%) compartments received radiation and had posttreatment neuropsychological evaluation. Median age at treatment was 7.4 years. The PRT patient cohort had higher estimated SES and shorter median time from radiotherapy completion to last neuropsychological evaluation (6.7 vs 2.6 y, P &lt; 0.001). On multivariable analysis, PRT was associated with higher full-scale IQ (\u03b2 = 10.6, P = 0.048) and processing speed (\u03b2 = 14.4, P = 0.007) relative to XRT, with trend toward higher verbal IQ (\u03b2 = 9.9, P = 0.06) and general adaptive functioning (\u03b2 = 11.4, P = 0.07). Planned sensitivity analyses truncating follow-up interval in the XRT cohort re-demonstrated higher verbal IQ (P = 0.01) and IQ (P = 0.04) following PRT, with trend toward improved processing speed (P = 0.09).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PRT is associated with favorable outcomes for intelligence and processing speed. Combined with other strategies for treatment de-intensification, PRT may further reduce neuropsychological morbidity of brain tumor treatment.<\/jats:p><\/jats:sec>","DOI":"10.1093\/neuonc\/noz070","type":"journal-article","created":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T23:13:36Z","timestamp":1555024416000},"page":"934-943","source":"Crossref","is-referenced-by-count":80,"title":["Improved neuropsychological outcomes following proton therapy relative to X-ray therapy for pediatric brain tumor patients"],"prefix":"10.1093","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9956-8346","authenticated-orcid":false,"given":"Jeffrey P","family":"Gross","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Zelko","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hartsell","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois"},{"name":"Radiation Oncology Consultants LLC, Chicago, Illinois"},{"name":"Northwestern Medicine Chicago Proton Center, Warrenville, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Fangusaro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine and the Aflac Cancer Center, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishi R","family":"Lulla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Warren Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha Pillay","family":"Smiley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Han-Chih","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinai","family":"Gondi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois"},{"name":"Radiation Oncology Consultants LLC, Chicago, Illinois"},{"name":"Northwestern Medicine Chicago Proton Center, Warrenville, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,4,17]]},"reference":[{"issue":"1-2","key":"2019071105360261700_CIT0001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF01406016","article-title":"Medulloblastoma in childhood. Survival and functional results","volume":"48","author":"Hirsch","year":"1979","journal-title":"Acta Neurochir (Wien)."},{"issue":"5","key":"2019071105360261700_CIT0002","first-page":"689","article-title":"Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma\/PNET: a report from the Childhood Cancer Survivor Study","volume":"19","author":"King","year":"2017","journal-title":"Neuro Oncol."},{"issue":"2","key":"2019071105360261700_CIT0003","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s11060-009-9927-z","article-title":"From childhood to adulthood: long-term outcome of medulloblastoma patients. The Institut Curie experience (1980-2000)","volume":"95","author":"Frange","year":"2009","journal-title":"J Neurooncol."},{"issue":"14","key":"2019071105360261700_CIT0004","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1200\/JCO.2008.21.1458","article-title":"Social outcomes in the Childhood Cancer Survivor Study cohort","volume":"27","author":"Gurney","year":"2009","journal-title":"J Clin Oncol."},{"issue":"13","key":"2019071105360261700_CIT0005","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/jnci\/djp148","article-title":"Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study","volume":"101","author":"Armstrong","year":"2009","journal-title":"J Natl Cancer Inst."},{"issue":"12","key":"2019071105360261700_CIT0006","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1001\/jama.290.12.1583","article-title":"Health status of adult long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study","volume":"290","author":"Hudson","year":"2003","journal-title":"JAMA."},{"issue":"5","key":"2019071105360261700_CIT0007","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1093\/neuonc\/nor015","article-title":"Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes","volume":"13","author":"Edelstein","year":"2011","journal-title":"Neuro Oncol."},{"issue":"3","key":"2019071105360261700_CIT0008","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s11060-004-3009-z","article-title":"Neuropsychological performance and quality of life of 10 year survivors of childhood medulloblastoma","volume":"72","author":"Maddrey","year":"2005","journal-title":"J Neurooncol."},{"issue":"4","key":"2019071105360261700_CIT0009","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1037\/0894-4105.17.4.548","article-title":"Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma","volume":"17","author":"Palmer","year":"2003","journal-title":"Neuropsychology."},{"issue":"7","key":"2019071105360261700_CIT0010","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S1470-2045(04)01507-4","article-title":"Late neurocognitive sequelae in survivors of brain tumours in childhood","volume":"5","author":"Mulhern","year":"2004","journal-title":"Lancet Oncol."},{"issue":"8","key":"2019071105360261700_CIT0011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jnci\/dju186","article-title":"Developing interventions for cancer-related dysfunction in childhood cancer survivors","volume":"106","author":"Castellino","year":"2014","journal-title":"J Natl Cancer Inst."},{"issue":"5","key":"2019071105360261700_CIT0012","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1200\/JCO.1998.16.5.1723","article-title":"Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study","volume":"16","author":"Mulhern","year":"1998","journal-title":"J Clin Oncol."},{"issue":"15","key":"2019071105360261700_CIT0013","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1200\/JCO.2001.19.15.3470","article-title":"Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children\u2019s Cancer Group study","volume":"19","author":"Ris","year":"2001","journal-title":"J Clin Oncol."},{"issue":"3","key":"2019071105360261700_CIT0014","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.ijrobp.2014.06.058","article-title":"Critical combinations of radiation dose and volume predict intelligence quotient and academic achievement scores after craniospinal irradiation in children with medulloblastoma","volume":"90","author":"Merchant","year":"2014","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"17","key":"2019071105360261700_CIT0015","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1200\/JCO.2013.52.3290","article-title":"Impact of craniospinal dose, boost volume, and neurologic complications on intellectual outcome in patients with medulloblastoma","volume":"32","author":"Moxon-Emre","year":"2014","journal-title":"J Clin Oncol."},{"issue":"186","key":"2019071105360261700_CIT0016","first-page":"1","article-title":"Relationships between regional radiation doses and cognitive decline in children treated with cranio-spinal irradiation for posterior fossa tumors","volume":"7","author":"Doger de Speville","year":"2017","journal-title":"Front Oncol."},{"issue":"34","key":"2019071105360261700_CIT0017","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1200\/JCO.2016.66.9077","article-title":"Intellectual outcome in molecular subgroups of medulloblastoma","volume":"34","author":"Moxon-Emre","year":"2016","journal-title":"J Clin Oncol."},{"issue":"5","key":"2019071105360261700_CIT0018","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/j.ijrobp.2005.05.028","article-title":"Radiation dosimetry predicts IQ after conformal radiation therapy in pediatric patients with localized ependymoma","volume":"63","author":"Merchant","year":"2005","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"4","key":"2019071105360261700_CIT0019","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.ijrobp.2009.06.003","article-title":"Investigating verbal and visual auditory learning after conformal radiation therapy for childhood ependymoma","volume":"77","author":"Di Pinto","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"1","key":"2019071105360261700_CIT0020","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ijrobp.2011.10.043","article-title":"A 5-year investigation of children\u2019s adaptive functioning following conformal radiation therapy for localized ependymoma","volume":"84","author":"Netson","year":"2012","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"5","key":"2019071105360261700_CIT0021","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/j.ijrobp.2012.10.031","article-title":"Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma","volume":"85","author":"Netson","year":"2013","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"1","key":"2019071105360261700_CIT0022","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/pbc.21530","article-title":"Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function","volume":"51","author":"Merchant","year":"2008","journal-title":"Pediatr Blood Cancer."},{"issue":"3","key":"2019071105360261700_CIT0023","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S1470-2045(15)00167-9","article-title":"Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study","volume":"17","author":"Yock","year":"2016","journal-title":"Lancet Oncol."},{"issue":"2","key":"2019071105360261700_CIT0024","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.ijrobp.2015.06.012","article-title":"Early cognitive outcomes following proton radiation in pediatric patients with brain and central nervous system tumors","volume":"93","author":"Pulsifer","year":"2015","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"10","key":"2019071105360261700_CIT0025","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1200\/JCO.2015.62.1383","article-title":"Comparing intelligence quotient change after treatment with proton versus photon radiation therapy for pediatric brain tumors","volume":"34","author":"Kahalley","year":"2016","journal-title":"J Clin Oncol."},{"issue":"1","key":"2019071105360261700_CIT0026","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.radonc.2017.06.010","article-title":"Attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy","volume":"124","author":"Antonini","year":"2017","journal-title":"Radiother Oncol."},{"issue":"2","key":"2019071105360261700_CIT0027","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ijrobp.2018.05.069","article-title":"Cognitive and adaptive outcomes after proton radiation for pediatric patients with brain tumors","volume":"102","author":"Pulsifer","year":"2018","journal-title":"Int J Radiat Oncol Biol Phys."},{"key":"2019071105360261700_CIT0028","author":"United States Census Bureau"},{"key":"2019071105360261700_CIT0029","author":"R Core Team","year":"2017"},{"key":"2019071105360261700_CIT0030","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-98141-3","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2009"},{"key":"2019071105360261700_CIT0031","doi-asserted-by":"crossref","first-page":"56","DOI":"10.32614\/RJ-2017-046","article-title":"Visualization of Regression Models Using visreg","volume":"9","author":"Breheny","year":"2017","journal-title":"The R Journal"},{"issue":"9","key":"2019071105360261700_CIT0032","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/nm749","article-title":"Irradiation induces neural precursor-cell dysfunction","volume":"8","author":"Monje","year":"2002","journal-title":"Nat Med."},{"issue":"731","key":"2019071105360261700_CIT0033","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1259\/0007-1285-61-731-1043","article-title":"Time- and dose-related changes in the white matter of the rat brain after single doses of X rays","volume":"61","author":"Calvo","year":"1988","journal-title":"Br J Radiol."},{"key":"2019071105360261700_CIT0034","doi-asserted-by":"crossref","first-page":"iv37","DOI":"10.1093\/neuonc\/nos196","article-title":"Radiation-induced cognitive impairment\u2014from bench to bedside","volume":"14","author":"Greene-Schloesser","year":"2012","journal-title":"Neuro Oncol."},{"key":"2019071105360261700_CIT0035","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1159\/000061239","article-title":"Pathological mechanisms leading to the development of late radiation-induced damage to the central nervous system.","volume-title":"Controversies in Neuro-Oncology","author":"Hopewell","year":"1999"},{"key":"2019071105360261700_CIT0036","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev.psych.53.100901.135204","article-title":"Child clinical\/pediatric neuropsychology: some recent advances","volume":"53","author":"Rourke","year":"2002","journal-title":"Annu Rev Psychol."},{"key":"2019071105360261700_CIT0037","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/87565649609540640","article-title":"Attentional skills and executive functioning in children with early hydrocephalus","volume":"12","author":"Fletcher","year":"1996","journal-title":"Dev Neuropsychol."},{"key":"2019071105360261700_CIT0038","volume-title":"Regional Development of the Brain in Early Life","author":"Minkowski","year":"1967"},{"issue":"2","key":"2019071105360261700_CIT0039","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1207\/S15326942DN1902_2","article-title":"Mechanisms of postnatal neurobiological development: implications for human development","volume":"19","author":"Webb","year":"2001","journal-title":"Dev Neuropsychol."},{"issue":"6","key":"2019071105360261700_CIT0040","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1017\/S1355617797005559","article-title":"Age-related differences in outcomes following childhood brain insults: an introduction and overview","volume":"3","author":"Taylor","year":"1997","journal-title":"J Int Neuropsychol Soc."},{"issue":"2","key":"2019071105360261700_CIT0041","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.radonc.2016.10.003","article-title":"Dose-dependent white matter damage after brain radiotherapy","volume":"121","author":"Connor","year":"2016","journal-title":"Radiother Oncol."},{"issue":"6","key":"2019071105360261700_CIT0042","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1002\/1531-8249(199912)46:6<834::AID-ANA5>3.0.CO;2-M","article-title":"Neurocognitive deficits in medulloblastoma survivors and white matter loss","volume":"46","author":"Mulhern","year":"1999","journal-title":"Ann Neurol."},{"key":"2019071105360261700_CIT0043","doi-asserted-by":"crossref","first-page":"iv25","DOI":"10.1093\/neuonc\/nos214","article-title":"Cerebral white matter integrity and executive function in adult survivors of childhood medulloblastoma","volume":"14","author":"Brinkman","year":"2012","journal-title":"Neuro Oncol."},{"key":"2019071105360261700_CIT0044","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.neurobiolaging.2015.11.021","article-title":"Altered tract-specific white matter microstructure is related to poorer cognitive performance: The Rotterdam Study","volume":"39","author":"Cremers","year":"2016","journal-title":"Neurobiol Aging."},{"issue":"3","key":"2019071105360261700_CIT0045","doi-asserted-by":"crossref","first-page":"e363","DOI":"10.1016\/j.ijrobp.2012.03.066","article-title":"Learning and memory following conformal radiation therapy for pediatric craniopharyngioma and low-grade glioma","volume":"84","author":"Di Pinto","year":"2012","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"10","key":"2019071105360261700_CIT0046","doi-asserted-by":"crossref","first-page":"e00531","DOI":"10.1002\/brb3.531","article-title":"Socioeconomic status, white matter, and executive function in children","volume":"6","author":"Ursache","year":"2016","journal-title":"Brain Behav."},{"issue":"2","key":"2019071105360261700_CIT0047","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1037\/a0026699","article-title":"Intelligence: new findings and theoretical developments","volume":"67","author":"Nisbett","year":"2012","journal-title":"Am Psychol."},{"issue":"2","key":"2019071105360261700_CIT0048","doi-asserted-by":"crossref","first-page":"e299","DOI":"10.1016\/j.ijrobp.2010.11.024","article-title":"Intensity-modulated arc therapy for pediatric posterior fossa tumors","volume":"82","author":"Beltran","year":"2012","journal-title":"Int J Radiat Oncol Biol Phys."},{"issue":"5","key":"2019071105360261700_CIT0049","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/S0360-3016(02)02828-6","article-title":"Acute effects of irradiation on cognition: changes in attention on a computerized continuous performance test during radiotherapy in pediatric patients with localized primary brain tumors","volume":"53","author":"Merchant","year":"2002","journal-title":"Int J Radiat Oncol Biol Phys."}],"container-title":["Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/neuro-oncology\/advance-article-pdf\/doi\/10.1093\/neuonc\/noz070\/28697076\/noz070.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/neuro-oncology\/article-pdf\/21\/7\/934\/28926266\/noz070.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,23]],"date-time":"2019-11-23T08:38:07Z","timestamp":1574498287000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article\/21\/7\/934\/5475068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,17]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,4,17]]},"published-print":{"date-parts":[[2019,7,11]]}},"URL":"https:\/\/doi.org\/10.1093\/neuonc\/noz070","relation":{},"ISSN":["1522-8517","1523-5866"],"issn-type":[{"value":"1522-8517","type":"print"},{"value":"1523-5866","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2019,4,17]]}}}