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.
Study Type
OBSERVATIONAL
Enrollment
140
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 (DLCO) evaluates diffusion deficits.
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.
University Children's Hospital Basel (UKBB)
Basel, Switzerland
RECRUITINGUniversitätsklinik für Kinderheilkunde
Bern, Switzerland
RECRUITINGGeneva University Hospital
Geneva, Switzerland
Change in Forced expiratory volume in 1 second (FEV1)
Dynamic lung function parameter: 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
Dynamic lung function parameter: 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)
Static lung function parameter: total lung capacity (TLC) to assess lung restriction
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
Static lung function parameter: residual volume (RV)/TLC to assess hyperinflation
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)
Global ventilation inhomogeneity assessed by 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
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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.
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.
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 surgical reports. Information about conditioning regimens including cumulative chemotherapy doses and total body irradiation of patients undergoing HSCT will be collected. Further information on the health state of the patient and interventions (e.g. development of pneumonia, antibiotic treatment) will be collected from the hospital charts.
Germline DNA is collected (e.g. through saliva or buccal cell sampling) for later analysis on genetic risk factors for pulmonary complications.
Centre hospitalier universitaire vaudois Lausanne
Lausanne, Switzerland
RECRUITINGUniversitäts-Kinderspital Zürich
Zurich, Switzerland
RECRUITINGAlveolar-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
Functional MRI: the primary outcome of functional lung imaging is the 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
Change in lung morphology assessed by MRI (description of structural changes: ground glass changes, thickened septal lines, interstitial infiltrates, diffuse alveolar infiltrates, haemorrhage, focal consolidation, fibrosis, pulmonary hypertension, pleural effusion, nodular changes, vasculitis (wall thickening) and thrombosis will be assessed)
Time frame: Before start of therapy, 12 months after end of intensive treatment,24 months after end of intensive treatment
Change in 4-hydroxy-2-nonenal in exhaled breath
Breath analysis: 4-hydroxy-2-nonenal is regarded as a surrogate marker for oxidative stress in the human body.
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
Untargeted explorative approach to assess 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)
Genetic variants associated with susceptibility to cancer therapy or related to lung development. Assessed in the Germline DNA Biobank Switzerland for childhood cancer and blood disorders (BISKIDS, as part of the Paediatric Biobank for Research in Haematology and Oncology \[BaHOP\], ethics approval PB\_2017-00533 to assess genetic determinants of pulmonary toxicity.
Time frame: At Baseline (start of therapy)