More Than Just X-Rays - Imaging of Chemotherapy-induced Morphological and Functional Cardiovascular and Lung Changes After Childhood ALL and Other Cancers - a Monocentric Late Effects Study (MaximALL)

University of Erlangen-Nürnberg Medical School180 enrolled

Overview

In this study, we investigate the cardiopulmonary health of survivors who underwent cancer treatment for acute lymphoblastic leukemia (ALL) or lymphoma during childhood, compared with healthy controls. Modern imaging techniques (MRI, MSOT, and echocardiography) as well as questionnaires assessing cardiopulmonary and mental health are used.

Survivors of childhood cancer have a high risk of developing late effects regarding different organ systems even years after treatment. Our preliminary data show that a high number of our study participants who have received oncological treatment for ALL or Hodgkin's disease, develop severe ventilation and/or perfusion disorders/defects that can be detected on MRI of the lungs. These changes are mainly observed in participants with a greater interval to the oncological treatment and we could find a significant correlation between ventilation- and perfusion defects and the timespan after diagnosis. In spiroergometry, our patient group showed reduced aerobic capacity (ViO2 max), regardless of the time of follow-up. Echocardiography including strain analysis resulted in suspicious findings. The aim of our follow-up project is to validate these results in a larger patient population and to extend the investigations of long-term follow up after oncological disease/treatment in childhood and adolescence. We are planning to conduct a multicenter study with participants (who received oncological treatment in childhood or adolescence and are now undergoing long-term-follow-up care (\> 5 years after treatment,). Therefore, we will examine morphological und functional lung changes by low field strength MRI and spiroergometry. We plan to investigate cardiac changes by echocardiography with strain analysis and ECG. Additionally, we would like to use multispectral optoacoustic tomography (MSOT) screening for muscle atrophy due to peripheral artery disease (PAD) as another modern imaging procedure for early detection of vascular changes.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

Interventions

QOL assessment, NeuropsychologicalOTHER

QoL assessment by EORTC SURV100, PPR

SpirometryDIAGNOSTIC_TEST

During this non-invasive test, the subject must breathe against resistance through a mouthpiece.

DLCO measurementDIAGNOSTIC_TEST

DLCO measurement is a non-invasive pulmonary function test for Pulmonary Diffusion Capacity.

EchocardioraphyDIAGNOSTIC_TEST

Echocardiography with strain-rate imaging.

MRIDIAGNOSTIC_TEST

LF-MRI for detection of morphological and functional changes in the lung and heart.

Clinical parametersOTHER

Recording patient information (Age, Gender, Weight and height, Ethnicity, current medication, measurement of blood pressure and blood oxygen saturation.

Blood samplesDIAGNOSTIC_TEST

Blood samples for further molecular testing regarding epigenetic aging markers and telomere biology parameters.

MSOTDIAGNOSTIC_TEST

multispectral optoacoustic tomography of musculus gastrocnemius bilaterally for screening of PAD

Eligibility

Sex: ALLMin age: 3 YearsHealthy volunteers:

Medical Language ↔ Plain English

Control Group: Inclusion Criteria: * no cancer diagnosis * no lung diseases * no vascular diseases * No subjective reduction in physical performance * age \>/= 18 years Exclusion Criteria: * Pregnancy, Lactation * Known pleural or pericardial effusion * Critical condition (requiring respiratory support, ventilation, oxygen, shock, symptomatic heart failure) * Marked thoracic deformities/malformations * Previous lung surgery * Injuries that do not allow physical stress diagnostics * Rejection of MRI imaging * General contraindications for MRI examinations (e.g. electrical implants such as cardiac pacemakers or perfusion pumps, copper IUD etc.) Survivors of ALL: Inclusion Criteria: * Completed therapy for ALL * age \>/= 3 years Exclusion Criteria: * Pregnancy, Lactation * Known pleural or pericardial effusion * Critical condition (requiring respiratory support, ventilation, oxygen, shock, symptomatic heart failure) * Marked thoracic deformities/malformations * Previous lung surgery * Injuries that do not allow physical stress diagnostics * Rejection of MRI imaging * General contraindications for MRI examinations (e.g. electrical implants such as cardiac pacemakers or perfusion pumps, copper IUD etc.) Survivors of Lymphoma: Inclusion Criteria: * Completed therapy for lymphoma * age \>/= 3 years Exclusion Criteria: * Pregnancy, Lactation * Known pleural or pericardial effusion * Critical condition (requiring respiratory support, ventilation, oxygen, shock, symptomatic heart failure) * Marked thoracic deformities/malformations * Previous lung surgery * Injuries that do not allow physical stress diagnostics * Rejection of MRI imaging * General contraindications for MRI examinations (e.g. electrical implants such as cardiac pacemakers or perfusion pumps, copper IUD etc.)

Outcomes

Primary Outcomes

Morphological lung changes (MRI)

Morphological lung changes

Time frame: Single time point

Functional lung parameters (MRI)

Ventilation match/mismatch, Perfusion match/mismatch, combined defects

Time frame: Single time point

Quantitative and functional cardiovascular changes (MRI)

Quantitative and functional cardiovascular changes of the heart

Time frame: Single time point

Secondary Outcomes

DLCO

diffusing capacity of the lungs for carbon monoxide (absolute value and % of predicted value)

Time frame: Single time point

Alveolar Volume

Time frame: Single time point

KCO

DLCO/VA (absolute and % of predicted value)

Time frame: Single time point

VC (vital capacity) in %

Time frame: single time point

FEV1

FEV1 (Forced Expiratory Volume in 1 Second) in %

Time frame: Single time point

VO2

Oxygen uptake (VO2)

Time frame: Single time point

VO2max

peak oxygen uptake (VO2max)

Time frame: Single time point

RER

Respiratory exchange ratio (RER)

Time frame: Single time point

VT2

Ventilatory anaerobic threshold (VT2)

Time frame: Single time point

VCO2

Carbon dioxide output (VCO2)

Time frame: Single time point

Heart rate (HR)

Time frame: Single time point

HRR

Heart Rate Reserve (HRR)

Time frame: Single time point

Breath rate at VAT

Time frame: Single time point

BRR

Breath rate reserve (BRR)

Time frame: Single time point

minute ventilation (VE)

Time frame: Single time point

O2 Pulse

Time frame: Single time point

HRV

Heart rate variability (HRV)

Time frame: Single time point

Borg Scale

Exercise capacity (Borg Scale)

Time frame: Single time point

Echocardiography

Myocardial function by echocardiographic strain and strain-rate imaging

Time frame: Single time point

Clinical parameters 1

Age in years

Time frame: Single time point

Clinical parameters 2

Gender

Time frame: Single time point

Clinical parameters 3

Weight

Time frame: Single time point

Clinical parameters 4

Ethnicity

Time frame: Single time point

Clinical parameters 5

Time from therapy initiation/Interval until study day

Time frame: Single time point

Clinical parameters 6

Current medication\*

Time frame: Single time point

Clinical parameters 7

Secondary diagnoses

Time frame: Single time point

Blood pressure

Blood pressure measurement

Time frame: Single time point

Clinical examination

Standard clinical examination

Time frame: Single time point

Questionnaire regarding psychosocial aspects

EORTC-SURV100 PPR (Posttraumatische Persönliche Reifung) Adapted Decision Regret questionnaire for childhood cancer survivors

Time frame: Single time point

Blood samples 1

Presence of clonal hematopoiesis (CH)

Time frame: Single time point

Blood samples 2

Type of CH-associated gene mutations (e.g. DNMT3A, TET2, DDR genes)

Time frame: Single time point

Blood samples 3

Clone size / variant allele frequency (VAF)

Time frame: Single time point

Blood samples 4

Epigenetic aging markers (e.g. epigenetic age acceleration measures)

Time frame: Single time point

Blood samples 5

Telomere biology parameters (e.g. telomere length-related measures)

Time frame: Single time point

Blood samples 6

biomarkers for long-term pulmonary dysfunction (WFDC2, TNFR1, MMP2, SPD18)

Time frame: Single time point

MSOT 1

Oxygenated haemoglobin (HbO₂)

Time frame: Single time point

MSOT 2

Deoxygenated haemoglobin (HHb)

Time frame: Single time point

MSOT 3

Total haemoglobin (tHb)

Time frame: Single time point

MSOT 4

Tissue oxygen saturation (sO₂)

Time frame: Single time point

MSOT 5

MSOT signal intensity per region of interest

Time frame: Single time point

MSOT 6

MSOT topogram of perfusion of the m. gastrocnemius

Time frame: Single time point

More Than Just X-Rays - Imaging of Chemotherapy-induced Morphological and Functional Cardiovascular and Lung Changes After Childhood ALL and Other Cancers - a Monocentric Late Effects Study (MaximALL)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts