Pulmonary toxicity in children, adolescents, and young adults with testicular germ cell tumors: A population-based retrospective matched cohort study

Abstract

While testicular germ cell tumors (TGCT) are highly curable, survivors experience toxicities. Pulmonary outcomes post-TGCT are not well understood, particularly among children, adolescents, and young adults (CAYA). Using provincial cancer registries, we identified all CAYA (aged 11-21 years) diagnosed with a TGCT from 1992 to 2021 in Ontario, Canada, and matched them (1:5) to general population males (controls). We linked CAYA to health administrative databases to identify pulmonary disease and pulmonary disease healthcare visits (PDV) and classified PDV severity as low (outpatient family physician/pediatrician), medium (outpatient respirologist/internist), or high (hospitalization/emergency department). We assessed acute (<5 years from diagnosis) and late (≥5 years after diagnosis) toxicities using the cumulative incidence function and cause-specific hazard models. We identified 748 patients (404 chemotherapy-treated) and 3740 controls. Patients' median age at diagnosis was 19.0 years [interquartile range (IQR):18.0-21.0] and 29.7 years (IQR:25.0-37.6) at end of follow-up. Non-chemotherapy-treated patients had higher risk of acute toxicities (obstructive lung disease, medium severity PDV, hospitalizations) but similar risk of late toxicities to controls. Chemotherapy-treated patients had higher risk than controls of most acute pulmonary toxicities (except asthma and low severity PDV) and several late toxicities: asthma [hazard ratio (HR) = 2.0, 95%CI:1.1-3.8], pulmonary embolism/infarction (HR = 7.3, 95%CI:1.2-44.3), medium severity PDV (HR = 3.9, 95%CI:2.1-7.3), and high severity PDV (HR = 1.7, 95%CI:1.0-2.8), particularly hospitalizations (HR = 4.1, 95%CI:1.7-9.5). CAYA TGCT survivors treated with chemotherapy are at risk for late asthma, pulmonary embolism, pulmonary fibrosis, and specialist and hospital-based pulmonary care. Further follow-up is needed to characterize late pulmonary outcomes as survivors age.

Keywords: adolescents and young adults; data linkage; germ cell tumors; pulmonary toxicity; real‐world outcomes.