Impact of Respiratory Developmental Stage on Sensitivity to Late Effects of Radiation in Pediatric Cancer Survivors

Abstract

PurposePulmonary dysfunction is a prevalent and potentially debilitating late effect of pediatric cancer treatment. We postulated that age, as a surrogate for respiratory developmental status, might be associated with vulnerability to pulmonary injury. Materials and MethodsSixty-one children treated with lung radiation at our institution who had undergone a pulmonary function test (PFT) between 1995 and 2016 were analyzed. Data collection included age at diagnosis and treatment, radiation dose and location, spirometry, and plethysmography results. PFTs were normalized according to age, sex, height, and ethnicity, and transformed into standardized z-scores. Obstructive disease was defined as forced expiratory volume in 1 second z score/forced vital capacity z score < −1.645, restrictive as total lung capacity z score < –1.645, and abnormal diffusion as diffusing capacity of the lung for carbon monoxide z score < −1.645. We determined the incidence of PFT abnormalities in our population and estimated the relative risk of developing pulmonary abnormalities using models adjusted for age. ResultsAt a mean age of 24 years (range, 12-31) and time from radiation of 9 years (range, 1-20), the cumulative incidence of any pulmonary abnormality was 34.4%. Among patients with an abnormal PFT, diffusing and restrictive abnormalities were most common (57.1% and 52.4%). When stratified by age at radiation treatment, 66.7% of patients <5 years had a PFT abnormality, compared with 47.6% for aged 5 to 13 and 20.6% for patients >13. Compared with patients >13 years, those <5 years and 5 to 13 years at radiation treatment had a significantly increased risk of an abnormal PFT with an odds ratio of 7.71 (95% confidence interval, 1.17, 51.06) and 3.51 (95% confidence interval, 1.06, 11.57), respectively (P <. 035). Furthermore, this association remained when examining each type of abnormality (P > .05). ConclusionsPFT abnormalities were common among our cohort of childhood cancer survivors treated with lung radiation. Younger age at treatment is associated with an increased risk of developing pulmonary dysfunction, presumably owing to developmental immaturity.