If You Torture Your Data Long Enough, It Will Confess to Anything: On the Epidemiological Basis of the LNT Model.

This note deals with epidemiological data interpretation supporting the linear no-threshold model, as opposed to emerging evidence of adaptive response and hormesis from molecular biology in vitro and animal models. Particularly, the US-Japan Radiation Effects Research Foundation's lifespan study of atomic bomb survivors is scrutinized. We stress the years-long lag of the data processing after data gathering and evolving statistical models and methodologies across publications. The necessity of cautious interpretation of radiation epidemiology results is emphasized.

A Revised System of Radiological Protection Is Needed.

ABSTRACT: The system of radiological protection has been based on linear no-threshold theory and related dose-response models for health detriment (in part related to cancer induction) by ionizing radiation exposure for almost 70 y. The indicated system unintentionally promotes radiation phobia, which has harmed many in relationship to the Fukushima nuclear accident evacuations and led to some abortions following the Chernobyl nuclear accident. Linear no-threshold model users (mainly epidemiologists) imply that they can reliably assess the cancer excess relative risk (likely none) associated with tens or hundreds of nanogray (nGy) radiation doses to an organ (e.g., bone marrow); for 1,000 nGy, the excess relative risk is 1,000 times larger than that for 1 nGy. They are currently permitted this unscientific view (ignoring evolution-related natural defenses) because of the misinforming procedures used in data analyses of which many radiation experts are not aware. One such procedure is the intentional and unscientific vanishing of the excess relative risk uncertainty as radiation dose decreases toward assigned dose zero (for natural background radiation exposure). The main focus of this forum article is on correcting the serious error of discarding risk uncertainty and the impact of the correction. The result is that the last defense of the current system of radiological protection relying on linear no-threshold theory (i.e., epidemiologic studies implied findings of harm from very low doses) goes away. A revised system is therefore needed.

COVID-19 and cancer risk arising from ionizing radiation exposure through CT scans: a cross-sectional study.

BACKGROUND: The surge in the utilization of CT scans for COVID-19 diagnosis and monitoring during the pandemic is undeniable. This increase has brought to the forefront concerns about the potential long-term health consequences, especially radiation-induced cancer risk. This study aimed to quantify the potential cancer risk associated with CT scans performed for COVID-19 detection. METHODS: In this cross-sectional study data from a total of 561 patients, who were referred to the radiology center at Imam Hossein Hospital in Shahroud, was collected. CT scan reports were categorized into three groups based on the radiologist's interpretation. The BEIR VII model was employed to estimate the risk of radiation-induced cancer. RESULTS: Among the 561 patients, 299 (53.3%) were males and the average age of the patients was 49.61 ± 18.73 years. Of the CT scans, 408 (72.7%) were reported as normal. The average age of patients with normal, abnormal, and potentially abnormal CT scans was 47.57 ± 19.06, 54.80 ± 16.70, and 58.14 ± 16.60 years, respectively (p-value < 0.001). The average effective dose was 1.89 ± 0.21 mSv, with 1.76 ± 0.11 mSv for males and 2.05 ± 0.29 mSv for females (p-value < 0.001). The average risk of lung cancer was 3.84 ± 1.19 and 9.73 ± 3.27 cases per 100,000 patients for males and females, respectively. The average LAR for all cancer types was 10.30 ± 6.03 cases per 100,000 patients. CONCLUSIONS: This study highlights the critical issue of increased CT scan usage for COVID-19 diagnosis and the potential long-term consequences, especially the risk of cancer incidence. Healthcare policies should be prepared to address this potential rise in cancer incidence and the utilization of CT scans should be restricted to cases where laboratory tests are not readily available or when clinical symptoms are severe.

Finite-Sample Bias of the Linear Excess Relative Risk in Cohort Studies of Computed Tomography-Related Radiation Exposure and Cancer.

The linear excess relative risk (ERR) is the most commonly reported measure of association in radiation epidemiological studies, when individual dose estimates are available. While the asymptotic properties of the ERR estimator are well understood, there is evidence of small sample bias in case-control studies of treatment-related radiation exposure and second cancer risk. Cohort studies of cancer risk after exposure to low doses of radiation from diagnostic procedures, e.g., computed tomography (CT) examinations, typically have small numbers of cases and risks are small. Therefore, understanding the properties of the estimated ERR is essential for interpretation and analysis of such studies. We present results of a simulation study that evaluates the finite-sample bias of the ERR estimated by time-to-event analyses and its confidence interval using simulated data, resembling a retrospective cohort study of radiation-related leukemia risk after CT examinations in childhood and adolescence. Furthermore, we evaluate how the Firth-corrected estimator reduces the finite-sample bias of the classical estimator. We show that the ERR is overestimated by about 30% for a cohort of about 150,000 individuals, with 42 leukemia cases observed on average. The bias is reduced for higher baseline incidence rates and for higher values of the true ERR. As the number of cases increases, the ERR is approximately unbiased. The Firth correction reduces the bias for all cohort sizes to generally around or under 5%. Epidemiological studies showing an association between radiation exposure from pediatric CT and cancer risk, unless very large, may overestimate the magnitude of the relationship, while there is no evidence of an increased chance for false-positive results. Conducting large studies, perhaps by pooling individual studies to increase the number of cases, should be a priority. If this is not possible, Firth correction should be applied to reduce small-sample bias.

[Risks of radiodiagnostic examinations in children]. / Risques des examens radiodiagnostiques chez l'enfant.

RISKS OF RADIODIAGNOSTIC EXAMINATIONS IN CHILDREN. The question of cancer risk associated with diagnostic medical exposure during childhood is important in view of the sharp increase in the use of radiological examinations, particularly computed tomography (CT), since the 2000s. Moreover, children represent a population particularly sensitive to ionizing radiation. Although conventional radiology examinations do not seem to be associated with an increased risk of cancer, several epidemiological studies, including some with high statistical power, show an increased risk of leukemia and brain tumors in children exposed to CT scans. These results reinforce the importance of the principles of radiation protection already applied daily in radiology, based on the justification of procedures, substitution as far as possible by techniques that do not expose patients to ionizing radiations (ultrasound and magnetic resonance imaging) and, if the use of CT scanners remains essential, systematic optimization of the doses delivered.

RISQUES DES EXAMENS RADIODIAGNOSTIQUES CHEZ L'ENFANT. La question du risque de cancer associé à l'exposition médicale à visée diagnostique pendant l'enfance est importante face à la forte augmentation de l'utilisation des examens radiologiques, notamment des scanners depuis les années 2000. De plus, les enfants représentent une population particulièrement sensible aux rayonnements ionisants. Si les examens de radiologie conventionnelle ne semblent pas associés à un sur-risque de cancer, plusieurs études épidémiologiques, dont certaines de grande puissance statistique, montrent une augmentation du risque de leucémie et de tumeur cérébrale pour des enfants exposés au scanner. Ces résultats renforcent l'importance du respect des principes de radioprotection déjà appliqués quotidiennement en radiologie reposant sur la justification des actes, la substitution autant que possible par des techniques n'exposant pas aux rayonnements ionisants (échographie et imagerie par résonance magnétique) et, si l'emploi du scanner reste indispensable, l'optimisation systématique des doses délivrées.

Maternal and Fetal Radiation-Induced Cancer Risk From Computed Tomography Pulmonary Angiography During Pregnancy: A Retrospective Cohort Study Across a Multihospital Integrated Health Care Network.

OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is important to evaluate suspected pulmonary embolism in pregnancy but has maternal/fetal radiation risks. The objective of this study was to estimate maternal and fetal radiation-induced cancer risk from CTPA during pregnancy. METHODS: Simulation modeling via the National Cancer Institute's Radiation Risk Assessment Tool was used to estimate excess cancer risks from 17 organ doses from CTPA during pregnancy, with doses determined by a radiation dose indexing monitoring system. Organ doses were obtained from a radiation dose indexing monitoring system. Maternal and fetal cancer risks per 100,000 were calculated for male and female fetuses and several maternal ages. RESULTS: The 534 CTPA examinations had top 3 maternal organ doses to the breast, lung, and stomach of 17.34, 15.53, and 9.43 mSv, respectively, with a mean uterine dose of 0.21 mSv. The total maternal excess risks of developing cancer per 100,000 were 181, 151, 121, 107, 94.5, 84, and 74.4, respectively, for a 20-, 25-, 30-, 35-, 40-, 45-, and 50-year-old woman undergoing CTPA, compared with baseline cancer risks of 41,408 for 20-year-old patients. The total fetal excess risks of developing cancer per 100,000 were 12.3 and 7.3 for female and male fetuses, respectively, when compared with baseline cancer risks of 41,227 and 48,291. DISCUSSION: Excess risk of developing cancer from CTPA was small relative to baseline cancer risk for pregnant patients and fetuses, decreased for pregnant patients with increasing maternal age, and was greater for female fetuses than male fetuses.

Lifetime attributable risks (LARs) of cancer in the fetus associated with maternal radiography examinations.

PURPOSE: For various reasons, pregnant women are occasionally exposed to ionizing radiation during radiology examinations. In these situations, it is essential to determine the radiation dose to the fetus and any associated risks. The present study attempts to calculate the mean dose for the fetus to estimate the possible cancer induction and cancer mortality risks resulting from maternal radiography exams. MATERIAL AND METHODS: The GATE Monte Carlo platform and a standard voxelized pregnant phantom were employed to calculate fetal radiation dose during maternal radiography exams. The data published in Biological Effects of Ionizing Radiation VII were used to convert fetal dose to lifetime attributable risks (LARs) of cancer incidence and cancer-related mortality. RESULTS: The fetal doses and LARs of cancer incidence and cancer-related mortality for the radiographs of the chest and skull were negligible. The maximum LAR values for the lateral view of the abdomen in computed and digital radiography are 5598.29 and 2238.95 per 100,000 individuals, respectively. The computed radiography of the lateral view of the abdomen revealed the highest LAR of cancer-related mortality (2074.30 deaths for every 100,000 people). CONCLUSION: The radiation dose incurred by the fetus due to chest and skull radiographs was minimal and unlikely to cause any abnormalities in the fetus. The discernible elevation in the lifetime attributable risk associated with cancer incidence and mortality arising from lateral computed radiography examinations of the abdomen warrants careful consideration within the realm of maternal radiography examinations.

Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Non-targeted effects and space radiation risks for astronauts on multiple International Space Station and lunar missions.

Future space travel to the earth's moon or the planet Mars will likely lead to the selection of experienced International Space Station (ISS) or lunar crew persons for subsequent lunar or mars missions. Major concerns for space travel are galactic cosmic ray (GCR) risks of cancer and circulatory diseases. However large uncertainties in risk prediction occur due to the quantitative and qualitative differences in heavy ion microscopic energy deposition leading to differences in biological effects compared to low LET radiation. In addition, there are sparse radiobiology data and absence of epidemiology data for heavy ions and other high LET radiation. Non-targeted effects (NTEs) are found in radiobiology studies to increase the biological effectiveness of high LET radiation at low dose for cancer related endpoints. In this paper the most recent version of the NASA Space Cancer Risk model (NSCR-2022) is used to predict mission risks while considering NTEs in solid cancer risk predictions. I discuss predictions of space radiation risks of cancer and circulatory disease mortality for US Whites and US Asian-Pacific Islander (API) populations for 6-month ISS, 80-day lunar missions, and combined ISS-lunar mission. Model predictions suggest NTE increase cancer risks by about ∼2.3 fold over a model that ignores NTEs. US API are predicted to have a lower cancer risks of about 30% compared to US Whites. Cancer risks are slightly less than additive for multiple missions, which is due to the decease of risk with age of exposure and the increased competition with background risks as radiation risks increase. The inclusion of circulatory risks increases mortality estimates about 25% and 37% for females and males, respectively in the model ignoring NTEs, and 20% and 30% when NTEs are assumed to modify solid cancer risk. The predictions made here for combined ISS and lunar missions suggest risks are within risk limit recommendations by the National Council on Radiation Protection and Measurements (NCRP) for such missions.

Evaluation of patient radiation dose and risk of cancer from CT examinations.

Computed tomography (CT) examinations have been increasingly requested and become the major sources of patient exposure. The cancer risk from CT scans is contingent upon the amount of absorbed dose of organs. This study aims to determine the organ doses and risk of cancer incidence and mortality from CT examinations at high dose (cumulative effective dose, CED ≥ 100 mSv) in a single day to low dose (CED < 100 mSv) from common CT procedures. Data were gathered from two academic centers of patients aged 15 to 75 years old performed CT examinations during the period of 5 years. CED and organ dose were calculated using Monte Carlo simulation software. Lifetime attributable risk (LAR) was determined following Biological Effects of Ionizing Radiation (BEIR) VII report based on life table and baseline cancer rates of Thai population. At high dose, the highest LAR for breast cancer incidence in young female was 82 per 100,000 exposed patients with breast dose of 148 mGy (CT whole abdomen). The highest LAR for liver cancer incidence in male patient was 72 per 100,000 with liver dose of 133 mGy (multiple CT scans). At low dose, the highest average LAR for breast cancer incidence in young female was 23 per 100,000 while for liver cancer incidence in male patients was 22 per 100,000 (CTA whole aorta). Even though the LAR of cancer incidence and mortality was less than 100 per 100,000, they should not be neglected. The risk of cancer incidence may be increased in later life, particularly in young patients.

A mathematical model for radiation-induced life-shortening attributed to cancer.

PURPOSE: In this paper, we described our mathematical model for radiation-induced life shortening in detail and applied the model to the experimental data on mice to investigate the effect of radiation on cancer-related life-shortening. MATERIALS AND METHODS: Our mathematical model incorporates the following components: (i) occurrence of cancer, (ii) progression of cancer over time, and (iii) death from cancer. We evaluated the progression of cancer over time by analyzing the cancer incidence data and cumulative mortalities data obtained from mice experiments conducted at the Institute for Environmental Sciences (IES). RESULTS: We analyzed non-irradiated control and 20 mGy/day × 400 days irradiated groups. In the analysis, all malignant neoplasms were lumped together and referred to as 'cancer'. Our analysis showed that the reduction in lifespan (104 days in median) was the result of the early onset of cancer (68 days in median) and the shortening of the cancer progression period (48 days in median). CONCLUSIONS: We described in detail our mathematical model for radiation-induced life-shortening attributed to cancer. We analyzed the mice data obtained from the experiment conducted at the IES using our model. We decomposed radiation-induced life-shortening into the early onset of cancer and the shortening of the cancer progression period.

Assessing the impact of neutron relative biological effectiveness on all solid cancer mortality risks in the Japanese atomic bomb survivors.

PURPOSE: Risk analyses, based on relative biological effectiveness (RBE) estimates for neutrons relative to gammas, were performed; and the change in the curvature of the risk to dose response with increasing neutron RBE was analyzed using all solid cancer mortality data from the Radiation Effect Research Foundation (RERF). Results were compared to those based on incidence data. MATERIALS AND METHODS: This analysis is based on RERF mortality data with separate neutron and gamma doses for colon doses, from which organ averaged doses could be calculated. A model for risk ratio variation with RBE was developed. RESULTS: The best estimate of the neutron RBE considering mortality data was 200 (95% confidence interval (CI): 50-1010) for colon dose using the weighted-dose approach and for organ averaged dose 110 (95% CI: 30-350). The ERR risk ratios for all solid cancers combined, for the best fitting neutron RBE estimate and the neutron RBE of 10 result in a ratio of 0.54 (95% CI: 0.17-0.85) for colon dose and 0.55 (95% CI: 0.18-0.87) for organ averaged dose. The risk to dose response curvature became significantly negative (concave down) with increasing RBE, at a neutron RBE of 170 using colon dose and at an RBE of 90 using organ averaged dose for males when fitting a linear-quadratic dose response. For females, the curvature decreased toward linearity with increasing neutron RBE and remained significantly positive until RBE of 80 and 40 using colon and organ averaged dose, respectively. For higher neutron RBEs, no significant conclusion could be drawn about the shape of the dose-response curve. CONCLUSIONS: Application of neutron RBE values higher than 10 results in substantially reduced cancer mortality risk estimates and a significant reduction in curvature of the risk to dose responses for males. Using mortality data, the best fitting neutron RBE is much higher than when incidence data is used. The neutron RBE ranges covered by the overlap in the CIs from both the mortality and incidence analyses are 50-190 using colon dose and in all cases, the best fitting neutron RBE and lower 95% CI are higher than the value of 10 traditionally applied by the RERF. Therefore, it is recommended to consider uncertainties in neutron RBE values when calculating radiation risks and discussing the shape of dose responses using Japanese A-bomb survivors data.

Secondary cancer risk assessments following the proton therapy of lung cancer as the functions of field characteristics and patient age.

INTRODUCTION: Radiation-induced secondary cancers relevant to proton therapy are still a main concern among cancer survivors. This study aims to determine the effects of age at exposure and treatment field size on radiation-induced secondary tumors following the proton therapy of lung cancer within out of field organs through the Monte Carlo (MC) simulation approach. MATERIAL AND METHODS: A full MC model of ICRP-110 male phantom was simulated to calculate the absorbed dose corresponding to secondary radiations within distant organs from the tumor volume. Then, the risks of secondary malignancies were estimated by employing the recommended risk model by the Committee of Biological Effects of Ionizing Radiation (BEIR) for different treatment field sizes and various patient ages at exposure. RESULTS: The results revealed that by increasing the patient age from 25 to 45 years, lifetime attributable risk (LAR) values were decreased. Maximum and minimum mortality rates were obtained for the liver and thyroid at the fixed age of 25 years, respectively. Calculated risk values for most near organs to the tumor were higher than those for distant organs. Changing the aperture size from 5 × 5 cm2 to 8 × 10 cm2 resulted in LAR increments with maximum variations of 12.5% for the stomach and a rough variation of 1.12 times in LAR for all exposure ages. CONCLUSION: Our work on whole-body phantom addresses the impact of age at exposure and aperture size on LAR during the proton therapy of lung cancer. To minimize secondary cancer risks relevant to proton therapy of lung cancer, extra attention should be considered.

Radiation-induced angiosarcoma of the breast: retrospective analysis at a regional treatment centre.

BACKGROUND: Radiation-induced angiosarcoma (RIA) is an uncommon but morbid complication after radiotherapy for breast cancer. METHODS: Retrospective analysis of breast RIA patients at Cambridge University Hospital (CUH), a regional treatment centre in the East of England. RESULTS: 22 patients were identified between 2010 and 2022. Median age of diagnosis was 65 years (range 41-78). Median time from breast radiotherapy to RIA diagnosis was 6.5 years (range 2.4-16.0)-this interval has decreased over the last 24 years (r2 = 0.6601). 9% had metastasis at presentation. All patients underwent surgery (55% at CUH, 45% at local hospitals). 27% received peri-operative pegylated liposomal doxorubicin in the first-line setting. 62% relapsed following their primary curative-intent treatments after a median of 28 months. Metastases occurred in 36%, the commonest sites being lung (100%) and lymph node (50%). 2-year and 5-year overall survival (OS) rates for all patients were 73% and 60%, respectively. No correlation between progression-free survival (PFS) and OS was found with tumour size, margin, peri-operative chemotherapy, and whether surgery was performed at CUH. Patients with multifocal disease on their breasts had shorter PFS following surgery compared to single-lesion disease (median 10 vs 65 months; HR = 4.359 [95% CI 1.342-14.16]; P = 0.0143). Patients aged > 72 years had a median OS of 45 months vs 102 months for those ≤ 72 years (HR = 7.129 [95% CI 1.646-30.88]; P = 0.0086). CONCLUSION: RIA has high rates of recurrence and mortality and appears to be occurring sooner after breast radiotherapy. Further studies on its pathogenesis and effective treatment are warranted.

An overview on the relationship between residential radon and lung cancer: what we know and future research

We aim to provide an overview of the research available on indoor radon and lung cancer, with a special focus on Spanish investigations. Early studies on underground miners established the link between radon and lung cancer, which was later confirmed for the general population by residential case–control studies. Spain contributed with extensive evidence, including 5 multicentric, hospital-based, case–control studies in the last 30 years, exploring diverse aspects, such as radon's effect on never-smokers, molecular pathways linking radon exposure to lung cancer risk, survival rates, mortality burden, and occupational exposure. There is a well-established causal association between radon with lung cancer. Despite pioneering research performed in our country by the Galician Radon Laboratory, particularly on driver genes, the evidence on the potential molecular pathways which makes radon a carcinogen is sparse. Also, relevant questions on the potential association of radon exposure with the induction of other diseases are still pending (AU)

Discussion of uncertainties and the impact of different neutron RBEs on all solid cancer radiation incidence risks obtained from the Japanese A-bomb survivor data.

The most recent publicly available data on all solid cancer incidence from the Life Span Study (LSS) of Japanese A-bomb survivors provides colon dose contributions weighted with a relative biological effectiveness (RBE) of 10 for neutrons, relative to gammas. However, there is evidence from several investigations that the neutron RBE for A-bomb survivors may be higher than 10. The change in the shape of the corresponding dose-response curves was evaluated by Hafner and co-workers in a previous study by applying sex-specific linear-quadratic dose models to previous LSS data for all solid cancer incidence that include separate neutron and gamma absorbed doses for several organs, in contrast to the most recent data. The resulting curvature change became significantly negative for males at an RBE of 140 for colon, 100 for liver, and 80 for organ averaged dose. For females, the corresponding RBE values were 110, 80, and 60 for colon, liver, and organ averaged doses. The present study compares three different methods to calculate the 95% confidence intervals in an analysis of the curvature with increasing RBE. Further, the impact of a higher neutron RBE on the work of the International Commission on Radiological Protection, and the importance of including uncertainties and performing sensitivity analysis of different parameters in radiation risk assessment are discussed.

INFLUENCE OF IONIZING RADIATION ON THE DEVELOPMENT OF BREAST CANCER. / ВПЛИВ ІОНІЗУЮЧОГО ВИПРОМІНЮВАННЯ НА РОЗВИТОК РАКУ МОЛОЧНОЇ ЗАЛОЗИ.

Breast cancer (BC) is one of the urgent problems of health care, which is due to a constant trend of growth. One of the risk factors for the development of breast cancer is ionizing radiation (IR). Numerous epidemiological and experimental studies have shown the high sensitivity of the mammary gland (MG) to this factor. Consideration of models of absolute and relative risks of the occurrence of radio-induced tumors of the MG in irradiated persons showed the importance of such factors as age at the time of irradiation, multiplicity. frequency of exposure, dose level and concomitant non-neoplastic diseases of the mammary and thyroid gland (TG). Excess radiation-induced cases of cervical cancer were found among irradiated women after the atomic bombings of Hiroshima and Nagasaki.Epidemiological features of the development of breast cancer under the influence of IV are presented in detail, which is one of the environmental factors involved in the formation of the modern carcinogenic situation. In con-nection with the significant sensitivity of the MG to the carcinogenic effect of IR, this form of neoplasms attracted special attention after the Chornobyl accident. The effect of small doses of radiation after the Chornobyl disaster led to a wave-like change in the incidence of breast cancer in certain periods of the year, and the radiation-induced incidence of this pathology can occur spontaneously.

Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults.

Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1-2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.