Whole-body MRI in Pediatric Hodgkin's Lymphoma

Study Overview
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Brief Summary
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Background: The assessment of extent of disease (staging) and response to therapy (restaging) is performed with computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET scan) or integrated FDG-PET/CT. Whole-body MRI with diffusion weighted imaging (WB-MRI with DWIBS) is a radiation-free method which allows imaging of the body with excellent soft tissue contrast in a single examination and could be an attractive alternative to FDG-PET and CT for the staging and restaging of malignant lymphomas in children. Aim of the study: The aims of this study are to compare the diagnostic performance of whole-body MRI (including DWIBS) to FDG-PET/CT and/or CT for the initial staging, early response assessment and restaging after completion of therapy in children with Hodgkin's lymphoma. Study design: Patients eligible for enrollment in this multicenter, prospective, diagnostic cohort study are children aged 8-18 years, with histologically confirmed Hodgkin's lymphoma, who are treated according to the EuroNet-PHL-C1 protocol (or trial with similar imaging strategy) in one of the participating centers. Patients will undergo WB-MRI in addition to the protocolar imaging routinely done (FDG-PET(/CT) and CT scan) at 3 time-points: at initial staging, after 2 chemotherapy cycles and at end of treatment. The investigators expect to enrol 75 patients in a 3 year study period. Staging and restaging results of WB-MRI (according to the Ann Arbor and Cheson classification, respectively) will be compared to those of FDG-PET(/CT) and CT. Clinical and radiological follow-up after 6 months will be used to solve any disagreements between FDG-PET, CT and WB-MRI. Additionally, the investigators will collect 3 year follow-up clinical data and data on follow-up imaging from the hospital charts of the patients, to better assess the prognostic value of FDG-PET and WB-MRI.

Detailed Description
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Background: The malignant lymphomas, Hodgkin´s lymphoma (HL) and non-Hodgkin´s lymphoma (NHL), comprise approximately 10% of childhood cancers. The assessment of extent of disease (staging) and response to therapy (restaging) is performed with computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET scan) or integrated FDG-PET/CT. Staging and restaging are important for choice of treatment and for determining prognosis. Unfortunately, FDG-PET and CT are accompanied by a significant amount of radiation exposure which may induce second cancers. New magnetic resonance imaging (MRI) techniques offer an alternative way for staging and follow-up of cancers. Whole-body MRI with diffusion weighted imaging (WB-MRI with DWIBS) is a radiation-free method which allows imaging of the body with excellent soft tissue contrast in a single examination and could be an attractive alternative to FDG-PET and CT for the staging and restaging of malignant lymphomas in children. Aim of the study: The aims of this study are to compare the diagnostic performance of whole-body MRI (including DWIBS) to FDG-PET/CT and/or CT for the initial staging, early response assessment and restaging after completion of therapy in children with Hodgkin's lymphoma. Study design: Patients eligible for enrollment in this multicenter, prospective, diagnostic cohort study are children aged 8-18 years, with histologically confirmed Hodgkin's lymphoma, who are treated according to the SKION / EuroNet-PHL-C1 protocol (or trial with similar imaging strategy) in one of the participating centers. Patients will undergo WB-MRI in addition to the protocolar imaging routinely done (FDG-PET(/CT) and CT scan) at 3 time-points: at initial staging, after 2 chemotherapy cycles and at end of treatment. We expect to enrol 75 patients in a 3 year study period. Staging and restaging results of WB-MRI (according to the Ann Arbor and Cheson classification, respectively) will be compared to those of FDG-PET(/CT) and CT. All imaging modalities will be assessed by a radiologist and nuclear medicine physician in a blinded fashion, using standardized score forms. Findings of FDG-PET and CT together will serve as the reference standard. Clinical and radiological follow-up after 6 months will be used to solve any disagreements between FDG-PET, CT and WB-MRI. Additionally, at least 3 year follow-up clinical data and data on follow-up imaging will be collected from the hospital charts of the patients, to better assess the prognostic value of FDG-PET and WB-MRI. Clinical/scientific relevance: This study aims to assess the accuracy of WB-MRI compared to FDG-PET(/CT) and CT in staging and response assessment of Hodgkin lymphoma. The results of this study can contribute to the development of evidence based 'radiation reduced' imaging protocols in Hodgkin's lymphoma.

Official Title
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Whole-body MRI for Initial Staging, Early Response Assessment and Restaging After Completion of Therapy in Pediatric Hodgkin's Lymphoma.

Conditions
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Hodgkin's Lymphoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female patients age: 8-18 years histologically proven Hodgkin's lymphoma enrolled in the EuroNet-PHL-C1 trial (or trial with comparable imaging strategy) patients scheduled for a FDG-PET/CT and/or CT of the body for initial staging, early response assessment (after two cycles of chemotherapy) or restaging participant's parents (and participants >12 years of age) must willingly give written informed consent prior to each MRI whole-body MRI/DWIBS has to be performed within 15 days before or after FDG-PET/CT or CT and the initial staging MRI should be performed before therapy has been started Exclusion Criteria: patients with a general contraindication for MRI (including cardiovascular pacemakers, claustrophobia) patients who have had a previous malignancy patients who are pregnant or nursing patients in whom therapy has already started after FDG-PET/CT and/or CT and before the initial WB-MRI/DWIBS could be performed apparent signs of resistance during MR examination

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric Hodgkin's lymphoma<br>Children with newly diagnosed Hodgkin's lymphoma | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Staging (Ann Arbor) | The primary outcome parameter will be the clinical stage according to WB-MRI (including DWIBS) and according to FDG-PET/CT. This clinical stage will be determined according to the Ann Arbor classification system for initial staging. | Day 1 | 
| Early treatment response assessment (Cheson criteria) | The primary outcome parameter will be the clinical stage according to WB-MRI (including DWIBS) and according to FDG-PET/CT. This clinical stage will be determined according to the Cheson criteria for early response assessment. | 2 months | 
| Restaging at end of therapy (Cheson criteria) | The primary outcome parameter will be the clinical stage according to WB-MRI (including DWIBS) and according to FDG-PET/CT. This clinical stage will be determined according to the Cheson criteria for restaging. | 6 months | 
| Follow up for 3 years after end of treatment | The percentage of relapse of Hodgkin lymphoma in this study cohort will be assessed by a 3-year follow-up of clinical and imaging data, and the percentage of true- versus false-positives on WB-MRI at end of treatment compared to PET/CT using this follow-up. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Image quality | The secondary outcome will be a (subjective) assessment of image quality and presence of artefacts, for both T1-weighted and T2-weighted MR images, MR-DWI as well as PET/CT. | Day 1, 2 months, 6 months | 
| Interobserver variability of WB-MRI for staging, early response assessment and restaging at end of therapy | The interobserver variability of WB-MRI (including DWIBS) for staging, early response assessment and restaging at end of therapy will be determined for two observers. | Day 1, 2 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant lymphoma, Hodgkin's disease, Imaging, Whole-Body MRI, PET/CT, Radiation