Is cancer a side effect of the treatment of cardiac problems in children?

Why people younger than 22 with congenital or acquired heart conditions should be more likely of developing a cancer? Actually, a small number of studies have been published, suggesting relatively high cancer incidence and mortality, compared to the general population.

If it is true a correlation exists, there are several potential explanations. It could be that some genetic factor is shared among this set of people; or an environmental one, like lifestyle or radiation exposure. Immunosuppression is also another possibility, linked to transplantations.

In order to find out what is going on, if anything, a team of researchers, including Manuel Higueras from the Basque Center for Applied Mathematics (BCAM), has undertaken the largest study to date¹ investigating cancer incidence among young people who have undergone cardiac catheterizations at five British hospitals, and the first to include detailed radiation dose estimation and transplant registry linkage. It confirms there is a large apparent impact of transplantation on cancer rates in this patient group.

Children with heart disease are subjected to a number of forms of medical x-ray examinations, including computed tomography (CT), cardiac catheterizations and general radiography. Although radiographs comprise the majority of procedures, the majority of the cumulative radiation dose in this patient group (around 80%) comes from CT and catheterizations.

A cardiac catheterization is a procedure to examine how well the heart is working. A thin, hollow tube called a catheter is inserted into a large blood vessel that leads to the heart. Usually, a coronary angiography is done during cardiac catheterization. A contrast dye visible in X-rays is injected through the catheter. X-ray images show the dye as it flows through the heart arteries. This shows where arteries are blocked.

Diagnostic medical radiation exposure has increased substantially in recent decades among this patient group. The long-term impact of this exposure is difficult to determine, however. In this study, the researchers established a cohort of 11,270 patients who had undergone cardiac catheterizations before 22 years of age. They then conducted two analyses; (1) an overall assessment of the incidence of all malignant tumours in the cohort, and (2) an assessment of the potential contribution of radiation exposure and organ transplantation on cancer rates. To assess the possible role of radiation exposure on cancer incidence, expected cases were also calculated from 5 years following the first recorded cardiac catheterization (2 years for leukaemia and lymphoma). These represent the apparent minimum latency periods for radiation induced tumours, based on previous epidemiological studies.

For cardiac catheterizations, active bone marrow (ABM) doses were estimated for 79% of examinations from dose indicators recorded at the time of each procedure, using a dosimetry system based on Monte Carlo computer simulations. For the remaining 21% of examinations for which no dose indicator was recorded, estimated doses were calculated based on the median doses for each procedure type at the same hospital, using the same equipment, in which dose indicators were recorded.

The excess relative risk of lymphohaematopoietic neoplasia (leukaemia and lymphoma, including borderline malignancies) in relation to cumulative ABM dose was calculated using Poisson regression models, fitted by maximum likelihood estimation. For this purpose the researchers used the maxLik function in the free software evironment for statistical computing R.

The researchers conclude that it is true. Cancer rates among children and young adults who undergo x-ray guided cardiac catheterizations are high, compared to the general population. Interestingly, despite transplant recipients making up less than 5% of the cohort, these individuals contributed more than 60% of observed malignancies. While immunosuppression may be the most likely explanation for this, the higher radiation doses received by transplant recipients, post-transplant, may also be a contributing factor.

Author: César Tomé López is a science writer and the editor of Mapping Ignorance.