Assessing Pulmonary Function in Children and Adolescents After Cancer Treatment: Protocol for a Multicenter Cohort...

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 about treatments, or a lack of standardization of pulmonary function tests (PFTs) or limited their investigation 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 test (N₂MBW) 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.

In 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 to other PFTs, and investigate the association of functional outcomes from PFTs with self-reported respiratory symptoms.

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 1 year has passed since a childhood cancer diagnosis, who have completed treatment, and who 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 undergo a standardized pulmonary assessment, including spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), and N₂MBW, and complete a questionnaire on respiratory symptoms and lifestyle. Data from previous and subsequent routine care PFTs will be included in this study.

Recruitment started 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. By October 2024, we had invited 220 patients, of which 201 have already participated in this study, resulting in a response rate of 91%. Their median age at the time of the study was 14 years (IQR 10-17), and the median time since diagnosis was 7 years (IQR 4-10). The study will continuously enroll new CCS.

This study will contribute to a comprehensive understanding of pulmonary function in CCS and assess related risk factors, as well as the utility of N₂MBW compared to other PFTs. The results will assist in the development of more targeted screening and risk-stratified follow-up care.

ClinicalTrials.gov NCT04732273; https://clinicaltrials.gov/study/NCT04732273.

DERR1-10.2196/69743.