Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

Periodic Report Summary 2 - EPI-CT (Epidemiological study to quantify risks for paediatric computerized tomography and to optimise doses.)

Project Context and Objectives:

Diagnostic radiation represents an indispensable, sometimes life-saving, tool in modern medicine. However, the growing use of computerized tomography (CT) scans is a topic of concern in radiological protection, especially for children and adolescents. Children are generally more sensitive to the carcinogenic effects of ionizing radiation than adults. In addition, they have a longer life-span to express any effect and, because of their smaller mass, they may receive higher radiation doses from a CT exam than an adult.

Although the individual risk from the CT exposure is likely to be small, the large number of people exposed annually means that even small individual risks could result in a considerable number of excess cancer cases. In the light of these considerations, there is a strong case to be made to develop knowledge about CT use patterns, accurately quantify doses to paediatric patients from these procedures, directly study their long-term health effects and better inform optimisation strategies for CT usage.

Two studies of health effects of CT-scanning have recently linked CT-radiation dose to cancer risk: leukaemia and brain tumour risk was associated with CT radiation in a UK cohort of over 175,000 young people; a linkage study of 680,211 young people in Australia, also suggested a relationship between CT-radiation dose and subsequent cancer risk.

Studies of CT use in paediatric patients are underway in the UK, Sweden, France, Canada, Germany, Australia and Israel. All of these are cohort-design studies, ranging in size from relatively small cohorts (e.g., in Israel) to quite large studies in the UK and Australia. Because the risks associated with the low doses of radiation from CT scans are expected to be small, a multi-national collaborative study is needed to ensure sufficient precision and statistical power to study these effects.

Compared to the UK and Australian studies, the EPI-CT is designed to derive improved individual organ-dose estimates for each cohort member and subsequently to more precisely quantify the associated health risks.

Scientists from 10 EU member states and one associated state with expertise in epidemiology, radiology, molecular biology, biostatistics, clinical medicine and dosimetry composed a consortium for the conduct of the international cohort study in order to directly quantify possible cancer risks from CT doses, particularly leukaemia and brain cancer, and communicate this information to stakeholders along with clear guidance on how this information may better inform CT dose optimisation in Europe. The present multi-national collaborative study aims to bring together the national paediatric CT patients’ studies already ongoing in Europe and to set-up additional studies in five other countries (Belgium, Denmark, the Netherlands, Spain and Norway).

In each participating hospital, for each eligible patient, computerized data is abstracted from the Radiological Information System (RIS) and, for recent periods, individual machine settings are extracted automatically from the Picture Archiving and Communication System (PACS).

Specific objectives of the project are to:

• Establish a large multinational cohort of paediatric patients who received CT scans;
• Describe patterns of use of CTs over time and between countries;
• Develop individual estimates of organ-specific doses from paediatric CT scans using improved methods for dose estimation for paediatric patients;
• Evaluate the radiation-related risk of cancer in this cohort and pilot test biological markers of CT-irradiation effects;
• Develop methods to characterize quality of CT images in relation to the corresponding examination dose;
• Provide recommendations for a “harmonized” approach to CT dose optimisation for paediatric patients in Europe.

Project Results:

The main focus for the effort undertaken in the reporting period was the work needed to continue the collection of information from radiology departments, and to start the collection of outcome, covariate and other information that may influence the association between the CT dose and cancer.

The collection of data has started in all the countries. Overall, 888.392 (86% of the expected cohort size) patients have already been included in the study. Four countries (the UK, Norway, France and the Netherlands) have gone past the planned number of patients, with Sweden soon to join them, and are continuing to expand their cohorts above the planned number of patients (Table 1). The automatic extraction of data from PACS has started in 24 hospitals in 8 countries.

The protocol outlining the EPI-CT methodology for organ dose reconstruction has been developed and published in an open access journal. Unfortunately, in many cases (especially in early years), a lot of necessary parameters for dose reconstruction will be missing. A questionnaire was developed to obtain, when possible, historical information on CT scan settings for the early time period.

We also focused on developing a method to account for missing and uncertain data. A proposed approach to account for uncertainties due to missing data is a simulation method, which maintains correlations of doses for persons within subgroups with similar attributes and simulates uncertain dose-model parameters values. This is being explored further.

Despite the efforts by manufacturers to improve the diagnostic efficacy of CT machines by introducing more sophisticated technologies aiming at reducing patient dose, radiation protection optimisation strategies still lack an optimized image quality system complying with the ALARA principle. To achieve this, there is a need to develop new dosimetric tools to better assess organ doses and to define a methodological approach to evaluate image content. We developed a methodology using two approaches that allow comparing physical (objective) and subjective tests of image quality assessment in relation to the patient dose. This document describes the following:

a) setting up a panel of international paediatric radiologists to refine the proposed set of quality criteria,
b) updating definition of degree of visibility of anatomical details by examination category taking into account the most recent CT generation performances and dose saving options made available by manufacturers,
c) designing an electronic tool aiming at facilitating quantitative scoring of the image quality as visually assessed by the radiologist,
d) validating the new set of quality criteria and associated electronic tool for a set of selected CT examinations collected in a sample of paediatric radiology departments participating to the EPI-CT project,

The meeting of Expert radiologists is setup in December 2013. The developed approach will be then tested in the radiology departments that agreed to collaborate in this exercise.

WP on biological mechanisms is currently testing different biomarkers of exposure and sensitivity for establishing mechanisms behind the low dose hypersensitivity in paediatric patients exposed to CT.

The results of the feasibility study demonstrated that cellular repair in young children is impaired at high doses (1 Gy) as detected by increased cytogenetic damage in umbilical cord blood and young children compared to adults. However, for low dose CT exposure (0.04 Gy), no clear statement can be given due to lack of statistical power in this pilot study.

The results show that there is an urgent need to organize an in vitro study with sufficient statistical power to investigate low dose radiation sensitivity of children by using dicentric aberrations as a reliable and sensitive biomarker.

Results of the in vitro inter-comparison showed that it is feasible to develop a working protocol to resolve damage response in the low dose range (10-100 mGy CT X-ray) by gammaH2AX foci analysis in an automatic manner which is suitable for a large molecular epidemiological study.

Work also focused on the different approaches and the results of whole genome analysis of in vitro x-irradiated samples. Whole blood samples were collected from healthy donors and irradiated with low (0.05 Gy) and high (1 Gy) doses of irradiation. RNA was isolated and hybridized to microarrays. The results of this report were published in the International Journal of Radiation Biology.

Potential Impact:

While physicians see benefits of using CT scanning in their clinical practice, concerns about the possible harmful effects of exposure to radiation from diagnostic radiologic procedures have existed for many decades. EPI-CT will help us better understand what these risks actually are. EPI-CT has been designed from the start to identify and characterise the potential magnitude of factors that may affect the precision of risk estimates so that they can be taken into account. It will therefore provide important information to assess the adequacy of current radiation risk estimates derived from studies of children with moderate to high doses received at high dose-rates from atomic bombings or radiotherapy to the generally lower doses received by CT patients.

The study will also provide a surveillance tool to monitor changes in exposures associated with these rapidly evolving technologies. Evaluating associations between the CT scan types, frequency, estimated bone marrow dose and leukaemia incidence have potentially important implications for the protection of paediatric patients.

A report detailing how to develop guidelines and recommendations for the optimal use of CT scans in paediatric patients will be prepared and presented to national and international radiation protection authorities.

Project results could be used as a basis for training radiologists and other technical personnel in how to optimise image quality and lower CT dose by adjusting scanning parameters.

There is no doubt that the use of CT imaging is beneficial for millions of patients annually. However, the results of this study jointly with CT paediatric protocol optimisation may help limit the radiation dose delivered to children and therefore reduce any potential risk arising from CT. At the same time it may be an important component to empower physicians and parents for informed decision making.

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