1. Lancet Oncol. 2022 Dec 6:S1470-2045(22)00655-6. doi: 10.1016/S1470-2045(22)00655-6. Online ahead of print. Brain cancer after radiation exposure from CT examinations of children and young adults: results from the EPI-CT cohort study. Hauptmann M(1), Byrnes G(2), Cardis E(3), Bernier MO(4), Blettner M(5), Dabin J(6), Engels H(6), Istad TS(7), Johansen C(8), Kaijser M(9), Kjaerheim K(10), Journy N(11), Meulepas JM(12), Moissonnier M(2), Ronckers C(13), Thierry-Chef I(14), Le Cornet L(15), Jahnen A(16), Pokora R(5), Bosch de Basea M(3), Figuerola J(3), Maccia C(17), Nordenskjold A(9), Harbron RW(18), Lee C(19), Simon SL(19), Berrington de Gonzalez A(19), Schüz J(2), Kesminiene A(2). Author information: (1)Institute of Biostatistics and Registry Research, Faculty of Health Sciences Brandenburg, Brandenburg Medical School, Neuruppin, Germany. Electronic address: Michael.Hauptmann@mhb-fontane.de. (2)International Agency for Research on Cancer (IARC/WHO), Environmental and Lifestyle Epidemiology Branch, Lyon, France. (3)Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Spanish Consortium for Research and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. (4)Institut de Radioprotection et de Sûreté Nucléaire, Fontenay aux Roses, France. (5)Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. (6)Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium. (7)Norwegian Radiation and Nuclear Safety Authority, Oslo, Norway. (8)Cancer Late Effect Research Oncology Clinic (CASTLE), Center for Surgery and Cancer, Rigshospitalet, Copenhagen, Denmark. (9)Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden. (10)Department of Research, Cancer Registry of Norway, Oslo, Norway. (11)Institut de Radioprotection et de Sûreté Nucléaire, Fontenay aux Roses, France; French National Institute of Health and Medical Research (Inserm), U1018, Centre for Research in Epidemiology and Population Health (CESP), Radiation Epidemiology Group, Gustave Roussy, Paris-Saclay, Paris-Sud University, Gustave Roussy, Villejuif, France. (12)Netherlands Cancer Institute, Amsterdam, the Netherlands. (13)Institute of Biostatistics and Registry Research, Faculty of Health Sciences Brandenburg, Brandenburg Medical School, Neuruppin, Germany. (14)International Agency for Research on Cancer (IARC/WHO), Environmental and Lifestyle Epidemiology Branch, Lyon, France; Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Spanish Consortium for Research and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. (15)Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; German Cancer Research Center, Heidelberg, Germany. (16)Luxembourg Institute of Science and Technology (LIST), Esch-sur-Alzette, Luxembourg. (17)CAATS, Centre d'Assurance de qualité des Applications Technologiques dans le domaine de la Santé, Sèvres, France. (18)Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK. (19)Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. BACKGROUND: The European EPI-CT study aims to quantify cancer risks from CT examinations of children and young adults. Here, we assess the risk of brain cancer. METHODS: We pooled data from nine European countries for this cohort study. Eligible participants had at least one CT examination before age 22 years documented between 1977 and 2014, had no previous diagnosis of cancer or benign brain tumour, and were alive and cancer-free at least 5 years after the first CT. Participants were identified through the Radiology Information System in 276 hospitals. Participants were linked with national or regional registries of cancer and vital status, and eligible cases were patients with brain cancers according to WHO International Classification of Diseases for Oncology. Gliomas were analysed separately to all brain cancers. Organ doses were reconstructed using historical machine settings and a large sample of CT images. Excess relative risks (ERRs) of brain cancer per 100 mGy of cumulative brain dose were calculated with linear dose-response modelling. The outcome was the first reported diagnosis of brain cancer after an exclusion period of 5 years after the first electronically recorded CT examination. FINDINGS: We identified 948 174 individuals, of whom 658 752 (69%) were eligible for our study. 368 721 (56%) of 658 752 participants were male and 290 031 (44%) were female. During a median follow-up of 5·6 years (IQR 2·4-10·1), 165 brain cancers occurred, including 121 (73%) gliomas. Mean cumulative brain dose, lagged by 5 years, was 47·4 mGy (SD 60·9) among all individuals and 76·0 mGy (100·1) among people with brain cancer. A significant linear dose-response relationship was observed for all brain cancers (ERR per 100 mGy 1·27 [95% CI 0·51-2·69]) and for gliomas separately (ERR per 100 mGy 1·11 [0·36-2·59]). Results were robust when the start of follow-up was delayed beyond 5 years and when participants with possibly previously unreported cancers were excluded. INTERPRETATION: The observed significant dose-response relationship between CT-related radiation exposure and brain cancer in this large, multicentre study with individual dose evaluation emphasises careful justification of paediatric CTs and use of doses as low as reasonably possible. FUNDING: EU FP7; Belgian Cancer Registry; La Ligue contre le Cancer, L'Institut National du Cancer, France; Ministry of Health, Labour and Welfare of Japan; German Federal Ministry of Education and Research; Worldwide Cancer Research; Dutch Cancer Society; Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat de Catalunya, Spain; US National Cancer Institute; UK National Institute for Health Research; Public Health England. Copyright © 2022 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/S1470-2045(22)00655-6 PMID: 36493793 Conflict of interest statement: Declaration of interests CJ reports honoraria from Pfizer, Janssen, and Astellas, and owns stocks in Y-mAbs, Novo Nordisk, Novozymes, Hansa, Zealand, Bavarian Nordic, and BioCryst Pharmaceuticals. MK reports grants from Stockholm County for clinical research within the frame of employment as a radiologist at the Karolinska University Hospital. CR reports a grant from the Dutch Cancer Society for Junior Group Leaders. All other authors declared no competing interests.