Early Pulmonary Dysfunction in Childhood Cancer Patients

Official title

Prospective Multicentre Cohort Study of Early Pulmonary Dysfunction in Childhood Cancer Patients (SWISS-Pearl Study)

Overview

This longitudinal, prospective, multicentre study is to monitor lung function prospectively in childhood cancer patients after diagnosis. The impact of cancer treatment on pulmonary dysfunction non-invasively using lung function, lung imaging and breath analysis as well as clinical symptoms using a questionnaire will be assessed at different time points.

Interventions

• Diagnostic test Lung function measurements
  All lung function tests are non-invasive and last about 60 minutes per child: * Multiple Breath Washout: The nitrogen multiple-breath-washout test (N2MBW) measures ventilation inhomogeneity of the lung that occurs when smaller airways are damaged. * Spirometry/Bodyplethysmography/DLCO: Spirometry measures dynamic air flows to quantify airway obstruction of large airways and pulmonary restriction. Plethysmography assesses static lung volumes. Diffusing capacity of the lung for carbon monoxide (D
• Diagnostic test Breath Analysis
  Patients will exhale into a secondary electrospray-ionization-mass spectrometry (SESI-MS) breath analysis platform. SESI-MS allows real-time breath-printing by detection of both volatile and non-volatile trace components.
• Diagnostic test Magnetic resonance imaging (MRI)
  Functional MRI scan assessing regional fractional lung ventilation and relative perfusion, followed by a morphological MRI scan. This technique allows simultaneous assessment of all affected lung components, the airways, alveoli and pulmonary vasculature.
• Other Standardized interview to assess respiratory symptoms
  Short questions on current airway symptoms, recent colds, exercise-related respiratory symptoms, and passive smoking exposure will be assessed. The interview takes about 10 minutes.
• Other Data collection for assessment of clinical parameters and cumulative doses to chemotherapy, radiation, surgery and HSCT
  Assessment of clinical parameters and cumulative doses to chemotherapy, radiation, surgery and hematopoietic stem cell transplantation (HSCT). Data on cumulative doses of pulmotoxic chemotherapy (carmustine, lomustine, busulfan, bleomycin, methotrexate and cyclophosphamide, fludarabine, ifosfamide, melphalan and thiotepa) and radiation therapy at the region of the chest from patient's hospital charts will be collected. Information on chest wall and lung surgery will be retrieved from the surgica
• Other Collection of genetic samples
  Germline DNA is collected (e.g. through saliva or buccal cell sampling) for later analysis on genetic risk factors for pulmonary complications.

Primary outcome measures

• Change in Forced expiratory volume in 1 second (FEV1) [Time frame: At Baseline (start of therapy), at month 3 (during intensive treatment), at month 6-18 (end of intensive treatment), 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Change in ratio of FEV1/forced vital capacity (FVC) for airway obstruction [Time frame: At Baseline (start of therapy), at month 3 (during intensive treatment), at month 6-18 (end of intensive treatment), 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Change in total lung capacity (TLC) [Time frame: At Baseline (start of therapy), at month 3 (during intensive treatment), at month 6-18 (end of intensive treatment), 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Change in residual volume (RV)/TLC [Time frame: At Baseline (start of therapy), at month 3 (during intensive treatment), at month 6-18 (end of intensive treatment), 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Change in lung clearance index (LCI) [Time frame: At Baseline (start of therapy), at month 3 (during intensive treatment), at month 6-18 (end of intensive treatment), 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Change in Alveolar-capillary membrane diffusion [Time frame: At Baseline (start of therapy), at month 3 (during intensive treatment), at month 6-18 (end of intensive treatment), 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Change in percentage portion of the lung volume with impaired ventilation or perfusion [Time frame: Before start of therapy, 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Change in lung morphology assessed by MRI [Time frame: Before start of therapy, 12 months after end of intensive treatment,24 months after end of intensive treatment]

Secondary outcome measures (3)

• Change in 4-hydroxy-2-nonenal in exhaled breath [Time frame: At Baseline (start of therapy), at month 3 (during intensive treatment), at month 6-18 (end of intensive treatment), 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Change in volatile organic compounds (VOCs) in exhaled breath [Time frame: At Baseline (start of therapy), at month 3 (during intensive treatment), at month 6-18 (end of intensive treatment), 12 months after end of intensive treatment,24 months after end of intensive treatment]
• Assessment of genetic variants through saliva or buccal cell sampling (collection of germline DNA) [Time frame: At Baseline (start of therapy)]

Eligibility criteria

Inclusion criteria

• at least one of the following cancer treatments:

• chest radiation
• treatment with any kind of chemotherapy
• hematopoietic stem cell transplantation (HSCT)
• thoracic surgery
• consent for Childhood Cancer Registry (ChCR) registration

Exclusion criteria

• no signed informed consent
• Operation outside the chest area as only cancer treatment
• Relapsed cancer (patients who develop relapse during the study will not be excluded)
• In addition for MRI and lung function tests:

• Subjects who are respiratory insufficient and cannot perform a lung function test (less than 92% O2 saturation; under O2 therapy)
• Pregnant
• MRI measurement not possible without sedation
• Metal (e.g. pacemaker) in the body

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Switzerland · 5 centers

• University Children's Hospital Basel (UKBB) — Basel
• Universitätsklinik für Kinderheilkunde — Bern
• Geneva University Hospital — Geneva
• Centre hospitalier universitaire vaudois Lausanne — Lausanne
• Universitäts-Kinderspital Zürich — Zurich

Identifiers

NCT: NCT05427136 · 2021-01206; ks22Usemann

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗