Maša Žarković, Christina Schindera, Nicolas Waespe, Daniel Trachsel, Anne Mornand, Marc Ansari, Philipp Latzin, Claudia E. Kuehni
Abstract Background Childhood cancer survivors (CCS) are at risk of pulmonary late effects, but post-treatment lung function remains understudied. Current guidelines recommend screening only for symptomatic survivors treated with lung-damaging treatments. We evaluated pulmonary function, risk factors, and respiratory symptoms in a broad paediatric CCS cohort, including those with standard treatments. Methods In this prospective multicenter study, we included CCS aged 6–21 years, stratified as high-risk (thoracic radiotherapy/surgery, busulfan/bleomycin/nitrosourea chemotherapy, haematopoietic stem cell transplantation [HSCT]) or standard-risk (other systemic treatment). Pulmonary function was assessed via spirometry (forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC]), body plethysmography (total lung capacity [TLC]), and diffusing capacity for carbon monoxide (DLCO), expressed as z-scores using Global Lung Initiative references. We assessed respiratory symptoms via questionnaires and analysed treatment associations with pulmonary function using multivariable linear regression. Results With a response rate of 90%, 251 CCS participated (median 7 years post-diagnosis). Mean z-scores for FEV 1 , FVC, TLC, and DLCO were lower in high-risk (-0.70, -0.91, -0.54, -0.17, respectively) than standard-risk survivors (-0.10, -0.22, -0.17, 0.32). Thoracic surgery and nitrosoureas were associated with lower TLC (-0.53, -1.37), HSCT with reduced FEV 1 and FVC (-0.80, –0.84), and thoracic radiotherapy with lower DLCO (-0.63). Respiratory symptoms were reported by 32%, but 64% of those with impaired lung function were asymptomatic. Conclusion Pulmonary function was mostly normal in standard-risk CCS, but impaired in high-risk, although often asymptomatic. These findings support targeted surveillance based on treatment exposure rather than symptoms to guide long-term care.