Understanding the health effects of low doses of ionizing radiation from medical procedures : Challenges for epidemiology

La aplicación de la radiación ionizante (RI) en ámbito médico ha llegado, sin duda, para salvar vidas. Sin embargo, hay una preocupación entre los expertos de salud pública y protección radiológica con relación al incremento de la exposición medica a RI, sobretodo en pacientes pediátricos. Esta tesis tiene como objetivo contribuir a una mejor caracterización del riesgo de radiación en pacientes oncológicos. Con ese fin, se creó un estudio de cohorte de supervivientes de cáncer infantil, como base para el análisis futuro y, anidado a esta cohorte, se implementó un estudio transversal sobre el efecto del neurodesarrollo después de haber recibido radioterapia no-craneal. Aquí se presenta un análisis descriptivo del estado de salud mental de la cohorte en forma de articulo científico. También se ha estimado la asociación entre la dosis acumulada de RI de los procedimientos de diagnóstico médico, como la exposición al radio-diagnostico y el cáncer (linfoma en adultos y tumores cerebrales en niños-adolescentes), en dos grandes estudios internacionales caso-control y dicho trabajo se unió a una estimación de dosimetría que puede ser aprovechada aún más para estudios similares. Este trabajo se presenta en forma de tres articulo científicos. En el marco de esta tesis, también, se sintetizó la evidencia actual de un efecto en el neurodesarrollo de la exposición a RI de dosis baja a moderada, en una revisión sistemática (en forma de artículo científico), concluyendo que la evidencia de este efecto es limitada e inadecuada. La estimación de los efectos de radiación médica requiere grandes esfuerzos y la colaboración entre epidemiólogos y clínicos es un aspecto clave en este tema.The application of ionising radiation (IR) in the medical sector is undoubtedly lifesaving. There are, however, risks associated with IR and there is growing concern among public health and radiation protection experts, in particular for the increasing medical radiological exposure in children. The aim of this dissertation is to contribute to a better characterisation of the IR risk in patients. A hospital-based cohort study of childhood cancer survivors was developed as a basis for future analysis and, nested within the cohort, a cross-sectional study on neurodevelopmental effect after non-cranial radiotherapy was implemented. A descriptive analysis of the mental health status of the cohort is presented here in the form of a Manuscript. The association between cumulative IR from medical diagnostic procedures and cancer (adult lymphoma and childhood/adolescent brain cancer), in two large international case-control studies, were estimated and a dosimetry estimation was developed. This work has lead to three manuscripts, included in the thesis. Evidence of a neurodevelopmental effect at low-to moderate IR dose was synthesized in a systematic review (presented here in a form of a Manuscript) and was found to be limited to inadequate. The estimated effect at this low dose range requires greater effort from epidemiologists to design more informative studies, and collaboration with clinicians is key for future research in radiation epidemiology

Understanding the health effects of low doses of ionizing radiation from medical procedures : Challenges for epidemiology

La aplicación de la radiación ionizante (RI) en ámbito médico ha llegado, sin duda, para salvar vidas. Sin embargo, hay una preocupación entre los expertos de salud pública y protección radiológica con relación al incremento de la exposición medica a RI, sobretodo en pacientes pediátricos. Esta tesis tiene como objetivo contribuir a una mejor caracterización del riesgo de radiación en pacientes oncológicos. Con ese fin, se creó un estudio de cohorte de supervivientes de cáncer infantil, como base para el análisis futuro y, anidado a esta cohorte, se implementó un estudio transversal sobre el efecto del neurodesarrollo después de haber recibido radioterapia no-craneal. Aquí se presenta un análisis descriptivo del estado de salud mental de la cohorte en forma de articulo científico. También se ha estimado la asociación entre la dosis acumulada de RI de los procedimientos de diagnóstico médico, como la exposición al radio-diagnostico y el cáncer (linfoma en adultos y tumores cerebrales en niños-adolescentes), en dos grandes estudios internacionales caso-control y dicho trabajo se unió a una estimación de dosimetría que puede ser aprovechada aún más para estudios similares. Este trabajo se presenta en forma de tres articulo científicos. En el marco de esta tesis, también, se sintetizó la evidencia actual de un efecto en el neurodesarrollo de la exposición a RI de dosis baja a moderada, en una revisión sistemática (en forma de artículo científico), concluyendo que la evidencia de este efecto es limitada e inadecuada. La estimación de los efectos de radiación médica requiere grandes esfuerzos y la colaboración entre epidemiólogos y clínicos es un aspecto clave en este tema.The application of ionising radiation (IR) in the medical sector is undoubtedly lifesaving. There are, however, risks associated with IR and there is growing concern among public health and radiation protection experts, in particular for the increasing medical radiological exposure in children. The aim of this dissertation is to contribute to a better characterisation of the IR risk in patients. A hospital-based cohort study of childhood cancer survivors was developed as a basis for future analysis and, nested within the cohort, a cross-sectional study on neurodevelopmental effect after non-cranial radiotherapy was implemented. A descriptive analysis of the mental health status of the cohort is presented here in the form of a Manuscript. The association between cumulative IR from medical diagnostic procedures and cancer (adult lymphoma and childhood/adolescent brain cancer), in two large international case-control studies, were estimated and a dosimetry estimation was developed. This work has lead to three manuscripts, included in the thesis. Evidence of a neurodevelopmental effect at low-to moderate IR dose was synthesized in a systematic review (presented here in a form of a Manuscript) and was found to be limited to inadequate. The estimated effect at this low dose range requires greater effort from epidemiologists to design more informative studies, and collaboration with clinicians is key for future research in radiation epidemiology

Ionising radiation as a risk factor for lymphoma: a review

The ability of ionising radiation to induce lymphoma is unclear. Here, we present a narrative review of epidemiological evidence of the risk of lymphoma, including chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM), among various exposed populations including atomic bombing survivors, industrial and medical radiation workers, and individuals exposed for medical purposes. Overall, there is a suggestion of a positive dose-dependent association between radiation exposure and lymphoma. The magnitude of this association is highly imprecise, however, with wide confidence intervals frequently including zero risk. External comparisons tend to show similar incidence and mortality rates to the general population. Currently, there is insufficient information on the impact of age at exposure, high versus low linear energy transfer radiation, external versus internal or acute versus chronic exposures. Associations are stronger for males than females, and stronger for non-Hodgkin lymphoma and MM than for Hodgkin lymphoma, while the risk of radiation-induced CLL may be non-existent. This broad grouping of diverse diseases could potentially obscure stronger associations for certain subtypes, each with a different cell of origin. Additionally, the classification of malignancies as leukaemia or lymphoma may result in similar diseases being analysed separately, while distinct diseases are analysed in the same category. Uncertainty in cell of origin means the appropriate organ for dose response analysis is unclear. Further uncertainties arise from potential confounding or bias due to infectious causes and immunosuppression. The potential interaction between radiation and other risk factors is unknown. Combined, these uncertainties make lymphoma perhaps the most challenging malignancy to study in radiation epidemiology

Neurodevelopmental effects of low dose ionizing radiation exposure: A systematic review of the epidemiological evidence

Background: The neurodevelopmental effects of high doses of ionizing radiation (IR) in children are well established. To what extent such effects exist at low-to-moderate doses is unclear. Considering the increasing exposure of the general population to low-to-moderate levels of IR, predominantly from diagnostic procedures, the study of these effects has become a priority for radiation protection. Objectives: We conducted a systematic review of the current evidence for possible effects of low-to-moderate IR doses received during gestation, childhood and adolescence on different domains of neurodevelopment. Data sources: Searches were performed in PubMed, Scopus, EMBASE and Psychinfo on the 6th of June 2017 and repeated in December 2018. Study eligibility criteria: We included studies evaluating the association between low-to-moderate IR doses received during gestation, childhood and adolescence, and neurodevelopmental functions. Study appraisal and synthesis methods: Studies were evaluated using the Cochrane Collaboration's risk of bias tool adapted to environmental sciences. A qualitative synthesis was performed. Results: A total of 26 manuscripts were finally selected. Populations analyzed in these publications were exposed to the following sources of IR: atomic bomb (Hiroshima and Nagasaki), diagnostic/therapeutic radiation, and Chernobyl and nuclear weapon testing fallout. There was limited evidence for an association between low-to-moderate doses of IR and a decrease in general cognition and language abilities, that is, a causal interpretation is credible, but chance or confounding cannot not be ruled out with reasonable confidence. Evidence for a possible stronger effect when exposure occurred early in life, in particular, during the fetal period, was inadequate. Evidence for an association between IR and other specific domains, including attention, executive function, memory, processing speed, visual-spatial abilities, motor and socio-emotional development, was inadequate, due to the very limited number of studies found. Limitations, conclusions, and implications of key findings: Overall, depending on the domain, there was limited to inadequate evidence for an effect of low-to-moderate IR doses on neurodevelopment. Heterogeneity across studies in terms of outcome and exposure assessment hampered any quantitative synthesis and any stronger conclusion. Future research with adequate dosimetry and covering a range of specific neurodevelopmental outcomes would likely contribute to improve the body of evidence. Systematic review registration number: The systematic review protocol was registered in PROSPERO (registration number CRD42018091902)