Assessing pulmonary function in children and adolescents after cancer treatment: protocol for a multicenter cohort study (SCCSS FollowUp–Pulmo) (Preprint)

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BACKGROUND Childhood cancer survivors (CCS) are at risk of pulmonary dysfunction due to cancer treatments, but evidence on prevalence and risk factors remains limited. Most previous studies had small sample sizes or retrospective study designs, little information on treatments, a lack of standardization of pulmonary function tests (PFTs), or limited pulmonary assessments to certain PFTs. Since spirometry mainly assesses the large airways, but cancer therapy also affects peripheral airways, additional functional tests are needed. The nitrogen multiple breath washout (N2MBW) test is sensitive to peripheral airway damage in other patient populations, but its benefit in CCS is unknown. Therefore, comprehensive and standardized evaluation of pulmonary function after cancer treatment in childhood using different PFTs that include N2MBW is needed to address these knowledge gaps and provide insights into possible early stages of pulmonary dysfunction. OBJECTIVE With the Swiss Childhood Cancer Survivor Study (SCCSS) FollowUp–Pulmo, we will comprehensively assess lung function in children and adolescents after treatment for cancer to identify risk factors for pulmonary dysfunction, assess the ability of N2MBW to detect pulmonary dysfunction compared with other PFTs, and investigate the association of functional outcomes from PFTs with self-reported respiratory symptoms. METHODS The SCCSS FollowUp–Pulmo is a prospective multicenter longitudinal cohort study embedded in routine clinical care that enrolls CCS aged 6‒20 years for whom at least one year has passed since childhood cancer diagnosis, who have completed treatment and attend regular pediatric oncological follow-up care. Inclusion criteria comprise any of the following: systemic anticancer treatment (chemotherapy, immunotherapy, or targeted agents), thoracic surgery, thoracic radiotherapy, or hematopoietic stem cell transplantation (HSCT). CCS receive a standardized pulmonary assessment including spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), and N2MBW, and a questionnaire on respiratory symptoms and lifestyle. Data from previous and subsequent routine care PFTs will be included in the study. RESULTS The study started recruitment in June 2022 at the University Children’s Hospital Bern, Switzerland. Subsequently, patient recruitment expanded to the University Children’s Hospitals in Basel and Geneva, Switzerland. The study continuously enrolls new CCS. By October 2024, we had invited 220 patients of which 201 participated, resulting in a response rate of 91%. Median age at study was 14 years (interquartile range [IQR] 10-17), and median time since diagnosis 7 years (IQR 4-10). CONCLUSIONS This study will contribute to a comprehensive understanding of pulmonary function in childhood cancer survivors and assess related risk factors, as well as the utility of N2MBW compared to other PFTs. The results will assist the development more targeted screening and risk-stratified follow-up care. CLINICALTRIAL ClinicalTrials.gov “NCT04732273”

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