Early Pulmonary Dysfunction in Childhood Cancer Patients

NCT05427136 | Recruiting

• 1 other identifier: 2021-01206; ks22Usemann
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Pulmonary Dysfunction

Keywords

Childhood cancer; Lung function; Lung imaging; Breath analysis; Exome-wide association studies (EWAS); Genome-wide association studies (GWAS); Pulmotoxic treatment

Outcome Measures

Primary Outcomes (8)

• Change in Forced expiratory volume in 1 second (FEV1)

  Dynamic lung function parameter: Forced expiratory volume in 1 second (FEV1)

  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

  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

  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

  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)

  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

  Alveolar-capillary membrane diffusion

  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.

  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)

  Before start of therapy, 12 months after end of intensive treatment,24 months after end of intensive treatment

Secondary Outcomes (3)

• Change in 4-hydroxy-2-nonenal in exhaled breath

  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

  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)

  At Baseline (start of therapy)

Interventions

Magnetic resonance imaging (MRI) DIAGNOSTIC_TEST

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.

Data collection for assessment of clinical parameters and cumulative doses to chemotherapy, radiation, surgery and HSCT OTHER

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.

Lung function measurements DIAGNOSTIC_TEST

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.

Breath Analysis DIAGNOSTIC_TEST

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.

Standardized interview to assess respiratory symptoms OTHER

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.

Collection of genetic samples OTHER

Germline DNA is collected (e.g. through saliva or buccal cell sampling) for later analysis on genetic risk factors for pulmonary complications.

Eligibility Criteria

• Age: 4 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Every new diagnosed cancer patient and every cancer patient planned for HSCT who is 4 years or older will be asked by the paediatric oncologist to participate in the study. This study will be conducted at the University Children's Hospital of Basel, Bern, Geneva, Lausanne and Zürich.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Children's Hospital Basel: lead

Study Sites (5)

University Children's Hospital Basel (UKBB)

Basel, 4056, Switzerland

RECRUITING

Universitätsklinik für Kinderheilkunde

Bern, 3010, Switzerland

RECRUITING

Geneva University Hospital

Geneva, 1211, Switzerland

RECRUITING

Centre hospitalier universitaire vaudois Lausanne

Lausanne, 1011, Switzerland

RECRUITING

Universitäts-Kinderspital Zürich

Zurich, 8032, Switzerland

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

For study participants who signed further the general consent form, biological materials and health-related data will be coded and stored in a secure biobank/database (BaHOP). The biological material and genetic data are kept in the BaHOP biobank for an indefinite period of time for further, until now not defined research questions.

MeSH Terms

Conditions

Neoplasms

Interventions

Breath Tests; Magnetic Resonance Imaging; Data Collection; Radiation; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Physical Phenomena

Study Officials

• Jakob Usemann, PD Dr. med.

  University Children's Hospital Basel, UKBB

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jakob Usemann, PD Dr. med.

CONTACT

+41 61 704 12 12; jakob.usemann@ukbb.ch

Christine Schneider

CONTACT

Christine.Schneider@insel.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: June 22, 2022
• Study Start: June 1, 2021
• Primary Completion (Estimated): June 1, 2051
• Study Completion (Estimated): June 1, 2051
• Last Updated: March 26, 2025

Record last verified: 2025-03

Locations

CH (5)