Assessing the Risk of Hematological Malignancies in Children and Adolescents Undergoing Computed Tomography: Insights from the EPI-CT Study

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Computed Tomography (CT) has revolutionized medical imaging since its introduction in the 1970s, playing a crucial role in diagnosing and managing various medical conditions. Despite its undeniable benefits, the escalating use of CT scans has prompted concerns regarding potential cancer risks, especially in pediatric populations.

The cumulative doses from multiple scans have led to a plateauing or reduction in pediatric CTs in many high-income countries. Alternative modalities like fast-acquisition magnetic resonance imaging and ultrasonography are increasingly being employed for specific pediatric indications.

Nevertheless, up to 7% of all CT procedures in high-income countries still involve children, emphasizing the need for a comprehensive understanding of the associated risks.

Radiation Dose Concerns:

While the link between moderate to high-dose ionizing radiation exposure and leukemia is well-established in both children and adults, the risk associated with low-dose exposure (common in diagnostic CT examinations) remains uncertain. This is particularly alarming given that CT scanning is a significant contributor to the world’s average annual effective dose per person from medical radiation sources. Addressing this concern is crucial for establishing guidelines that balance diagnostic benefits with potential health risks.

Existing Studies and Criticisms:

Several studies have attempted to estimate the risk of hematological malignancies associated with CT scan radiation in children and young adults. However, criticism has been directed at these studies for factors such as low statistical power, inadequate individual dosimetry, and potential bias from confounding by indication. Confounding by indication refers to situations where individuals undergoing CT examinations may be at a higher risk of cancer due to underlying conditions, introducing bias into the results.

The EPI-CT Study:

In response to the limitations of previous studies, the International Agency for Research on Cancer (IARC) initiated the EPI-CT study. This large-scale study involved 948,174 individuals from nine European countries, aiming to provide more accurate and direct estimates of cancer risk associated with low-dose radiation exposure from CT scanning in childhood, adolescence, and early adulthood.

Analyzing Hematological Malignancies:

This article presents the analyses of the EPI-CT study focused on the risk of hematological malignancies in relation to radiation exposure from CT examinations in the specified age groups. The study’s extensive dataset and multinational approach allow for a more comprehensive understanding of the potential risks associated with pediatric CT scans.

Challenges and Controversies:

The linear extrapolation of risk from higher doses, as seen in the Japanese atomic bomb survivor studies, forms the basis of current international radiological protection recommendations. However, the assumption of no dose threshold below which the risk of radiation-induced cancer is zero (the linear no-threshold model) remains controversial. The EPI-CT study aims to contribute valuable insights to this debate and provide a more nuanced understanding of the risks associated with low-dose radiation exposure.

Discussion

The EPI-CT study represents a significant step forward in understanding the potential risks associated with ionizing radiation exposure from pediatric and young adult CT examinations. This extensive multi-center study, involving nearly one million patients, aimed to directly estimate the risk of hematological malignancies, addressing previous methodological criticisms related to dosimetry, statistical power, and potential biases.

Dose-Response Relationship: The results of the EPI-CT study revealed a clear dose-response relationship between cumulative active bone marrow (ABM) dose and the risk of hematological malignancies, encompassing both lymphoid and myeloid malignancies.

Notably, the increased risk was observed at relatively low doses, as low as 10–15 mGy, emphasizing the sensitivity of the hematopoietic system to ionizing radiation.

Robustness of Findings: Associations between the risk of hematological malignancies and estimated CT radiation dose were robust across various sensitivity analyses. Even when doses were lagged by 5 years or when excluding individuals with the highest cumulative doses, the increased risk persisted. This robustness suggests that the observed associations are not artifacts resulting from outliers or temporal variations.

Comparison with Previous Studies: Comparison with previous national studies revealed variations in leukemia risk estimates, with differences attributed to cohort size, follow-up duration, and dosimetry methods. Notably, the expanded cohort and longer follow-up in the EPI-CT study contributed to discrepancies in risk estimates between EPI-CT and the original UK and Dutch cohorts. The sophisticated dosimetry modeling used in EPI-CT, accounting for historical CT practices and uncertainties, provided more accurate dose estimates and contributed to aligning results with the full EPI-CT study.

Unexpected Findings and Influences: The observation of an increased risk of Hodgkin’s lymphoma (HL) in the EPI-CT study, contrary to the absence of an association in the original UK cohort and inconsistent results in older adults in other studies, raises intriguing questions. The influence of the UK cohort on overall risk estimates suggests potential discrepancies in technical parameters during pediatric CT examinations in the UK, possibly leading to systematic underestimation of doses. Missing examinations and the age limitation for inclusion in the study might contribute to the differences observed.

Addressing Methodological Challenges: EPI-CT was designed to overcome methodological challenges, including potential biases such as reverse causation. While efforts were made to address confounding by indication, limitations in the available data prevented a comprehensive evaluation. Nonetheless, the study’s findings were robust to different assumptions and exclusions.

Limitations and Uncertainties: Despite rigorous efforts, the study has limitations. Confounding by indication could not be fully addressed, and uncertainties in individual doses, particularly in early years, may impact risk analyses. Further validation of retrospective dose estimates and systematic prospective collection of dose quantities and technical parameters are necessary for improved risk estimates in future studies.

Age-Related and Temporal Considerations: The observation that the excess relative risk per 100 mGy increased with age at exposure and was highest for exposures within 10 years of diagnosis emphasizes the need for extended follow-up to explore age-related effects comprehensively.

Comparison with Atomic Bomb Survivor Study: Comparing EPI-CT results with the atomic bomb survivor study, the linear no-threshold model did not appear to overestimate the risk from pediatric CT radiation. Despite differences in dosimetry systems, the leukemia risk estimate in EPI-CT was compatible with recent combined analyses of individuals exposed before the age of 21 and ABM dose <100 mGy.

Implications and Recommendations: The consistent and robust dose-related increased risk of radiation-induced hematological malignancies, particularly in the context of low-dose exposures associated with pediatric CT scans, underscores the importance of strict radiological protection measures. Adherence to the ALARA principle, justification and optimization of radiological procedures, monitoring delivered doses, and maximizing the benefit-to-risk ratio for all CT examinations, especially in pediatric populations, are crucial.

Conclusion: In conclusion, the EPI-CT study provides comprehensive insights into the risks associated with pediatric and young adult CT radiation exposure. The findings support and strengthen previous evidence of a dose-related increased risk of hematological malignancies. These results emphasize the imperative for ongoing efforts to minimize radiation exposure in medical settings, ensuring patient safety while maintaining the diagnostic efficacy of CT scans. Continued awareness and adherence to radiological protection principles are essential for the well-being of patients, particularly in vulnerable populations such as children and young adults. The EPI-CT study serves as a vital contribution to the ongoing dialogue surrounding the risks and benefits of medical imaging, guiding future research and clinical practices in the field of radiology.


reference link : https://www.nature.com/articles/s41591-023-02620-0

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