Pulmonary function in young childhood cancer survivors: results from a prospective multicentre cohort

Abstract

Background Childhood cancer survivors (CCSs) 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 representative paediatric CCS cohort, including those with standard treatments. Methods In this prospective multicentre study, we included CCSs aged 6-21 years, stratified as high-risk (thoracic radiotherapy/surgery, busulfan/bleomycin/nitrosourea chemotherapy and haematopoietic stem cell transplantation (HSCT)) or standard-risk (other systemic treatment). Pulmonary function was assessed via spirometry (forced expiratory volume in 1 s (FEV1) and 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 CCSs participated (median 7 years post-diagnosis). Mean z-scores for FEV1, FVC, TLC and DLCO were lower in high-risk (−0.70, 95% confidence interval −0.96 to −0.43; −0.91, −1.16 to −0.66; −0.54, −0.78 to −0.31; and −0.17, −0.55 to 0.22, respectively) than standard-risk survivors (−0.10, −0.26 to 0.06; −0.22, −0.37 to −0.06; −0.17, −0.33 to −0.01; and 0.32, 0.15 to 0.49). Thoracic surgery and nitrosoureas were associated with lower TLC (−0.53 and −1.37), HSCT with reduced FEV1 and FVC (−0.80 and −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 CCSs, whereas high-risk survivors showed mild reductions, often asymptomatic. These findings support targeted surveillance based on treatment exposure rather than symptoms to guide long-term care.