Cumulative Radiation Exposure and Lifetime Cancer Risk in Patients With Tetralogy of Fallot Requiring Early Intervention

Abstract

Background: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, utilizing either a staged repair (SR) or primary repair (PR) approach. They are exposed to several sources of low-dose ionizing radiation, which may contribute to increased cancer risk.

Objectives: The purpose of this study was to compare cumulative radiation exposure and associated lifetime attributable risk (LAR) of cancer between treatment strategies in sTOF.

Methods: Neonates with sTOF who underwent SR or PR from 2012 to 2017 were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Radiation exposure from all radiologic studies prior to 18 months of age was converted to organ-equivalent doses and projected LAR of cancer incidence using the National Cancer Institute dosimetry tools.

Results: There were 242 neonates from 8 centers, including patients with 146 SR and 96 PR. Cumulative total effective dose was significantly higher for SR (median 8.3 mSv, IQR: 3.0-17.4 mSv) than PR (2.1 mSv, IQR: 0.8-8.5 mSv; P < 0.001). Cumulative organ-level doses were significantly higher in SR compared to PR. Regardless of treatment strategy, LARs were higher in females compared to males. Among organs with median exposure >1 mGy in females, the LAR was highest for breast in SR (mean 1.9/1,000 patients). The highest proportion of cancers attributable to radiation exposure was projected for thyroid cancer in females undergoing SR (7.3%).

Conclusions: Cumulative radiation exposure and LARs were higher among those undergoing SR compared to PR. This will be an important factor to consider in determining the preferred neonatal treatment strategy and should substantiate efforts to reduce radiation exposure in this vulnerable population.

Keywords: cancer; congenital heart disease; outcomes; radiation exposure; staged repair.

Graphical abstract

Central Illustration

Cumulative Radiation Exposure in Tetralogy of Fallot Patients Requiring Early Intervention Distribution of cumulative radiation exposure by organ and treatment strategy in (A). The total cumulative effective and select organ-equivalent doses are provided in (B). Boxes represent the 25th to 75th percentiles, with the median depicted as a horizontal line. The whisker represents 1.5x the interquartile range or the minimum and maximum values, whichever is shorter. Values are median (interquartile range). P values comparing between treatment strategies are provided. The primary repair group is displayed in blue, and the staged repair group is in red. ^aFemale patients only, n = 45 (primary repair) n = 72 (staged repair).

Figure 1

Projected Incident Excess Cancer Risk Subsequent to Radiation Exposure by Attained Age, Displayed by Sex and Treatment Strategy Thyroid cancers are displayed in yellow, lung cancers in blue, breast cancers in red, and stomach cancers in green.

Figure 2

Cumulative Effective Dose Across Type of Radiation-emitting Study, by Treatment Strategy Boxes represent the 25th to 75th percentiles, with the median depicted as a horizontal line. The whisker represents 1.5x the interquartile range or the minimum and maximum values, whichever is shorter. P values comparing treatment strategies are displayed above. the number of patients included within each category are listed below. The primary repair group is displayed in blue, and the staged repair group is in red. CC = cardiac catheterization; CT = computed tomography; IR = interventional radiology; NM = nuclear medicine; XR = x-ray.

Figure 3

Distribution of the Proportion of Patients Who Had a Cardiac Catheterization, CT, or NM Study by Treatment Strategy Use of none of these studies is displayed in gray, cardiac catheterizations only in dark blue, cardiac catheterization with CT and/or NM in blue, CT only in orange, NM only in dark green, and NM and/or CT in green.