Radiographic screening of infants and young children with genetic predisposition for rare malignancies: DICER1 mutations and pleuropulmonary blastoma

• Published in: American journal of roentgenology (1976) Vol. 204; no. 4; pp. W475 - W482
• Main Authors: Sabapathy, Divya G, Guillerman, R Paul, Orth, Robert C, Zhang, Wei, Messinger, Yoav, Foulkes, William, Priest, John R, Annapragada, Ananth V
• Format: Journal Article
• Language: English
• Published: United States 01.04.2015
• Subjects: Child, Preschool; DEAD-box RNA Helicases - genetics; Decision Support Techniques; Female; Genetic Predisposition to Disease; Humans; Infant; Life Expectancy; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Mutation; Neoplasms, Radiation-Induced - etiology; Pulmonary Blastoma - diagnostic imaging; Pulmonary Blastoma - genetics; Pulmonary Blastoma - mortality; Radiation Dosage; Radiography, Thoracic; Ribonuclease III - genetics; Risk; Sensitivity and Specificity; Tomography, X-Ray Computed; rare diseases; CT; screening; radiation risk; chest radiograph
• ISSN: 0361-803X; 1546-3141
• DOI: 10.2214/AJR.14.12802

The purpose of this study was to compare the risks of radiation in screening strategies using chest radiographs and CT to detect a rare cancer in a genetically predisposed population against the risks of undetected disease. A decision analytic model of diagnostic imaging screening strategies was built to predict outcomes and cumulative radiation doses for children with DICER1 mutations screened for pleuropulmonary blastoma. Screening strategies compared were chest radiographs followed by chest CT for a positive radiographic result and CT alone. Screening frequencies ranged from once in 3 years to once every 3 months. BEIR VII (model VII proposed by the Committee on the Biological Effects of Ionizing Radiation) risk tables were used to predict excess cancer mortality for each strategy, and the corresponding loss of life expectancy was calculated using Surveillance Epidemiologic and End Results (SEER) statistics. Loss of life expectancy owing to undetected progressive pleuropulmonary blastoma was estimated on the basis of data from the International Pleuropulmonary Blastoma Registry. Sensitivity analysis was performed for all model parameters. Loss of life expectancy owing to undetected disease in an unscreened population exceeded that owing to radiation-induced cancer for all screening scenarios investigated. Increases in imaging frequency decreased loss of life expectancy for the combined (chest radiographs and CT) screening strategy but increased that for the CT-only strategy. This was because loss of life expectancy for combined screening is dominated by undetected disease, whereas loss of life expectancy for CT screening is dominated by radiation-induced cancers. Even for a rare disease such as pleuropulmonary blastoma, radiographic screening of infants and young children with cancer-predisposing mutations may result in improved life expectancy compared with the unscreened population. The benefit of screening will be greater for diseases with a higher screening yield.