Whole-body MRI in Pediatric Hodgkin's Lymphoma

Sponsor

UMC Utrecht (Other)

Overall Status

Completed

CT.gov ID

NCT04005703

Collaborator

Stichting Kinderen Kankervrij (KiKa) (Other)

Enrollment

Locations

111

Actual Duration (Months)

9.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin's Lymphoma

Detailed Description

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:

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.

Study Design

Study Type:

Observational

Actual Enrollment :

75 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

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

Actual Study Start Date :

Jun 1, 2011

Actual Primary Completion Date :

Dec 1, 2016

Actual Study Completion Date :

Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Pediatric Hodgkin's lymphoma Children with newly diagnosed Hodgkin's lymphoma

Outcome Measures

Primary Outcome Measures

Staging (Ann Arbor) [Day 1]
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.
Early treatment response assessment (Cheson criteria) [2 months]
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.
Restaging at end of therapy (Cheson criteria) [6 months]
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.
Follow up for 3 years after end of treatment [3 years]
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.

Secondary Outcome Measures

Image quality [Day 1, 2 months, 6 months]
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.
Interobserver variability of WB-MRI for staging, early response assessment and restaging at end of therapy [Day 1, 2 months, 6 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	LKH-Universitätsklinikum Graz	Graz	Austria
2	Ospedale Giannina Gaslini	Genova	Italy
3	Academic Medical Center Amsterdam	Amsterdam	Netherlands
4	VU University Medical Center	Amsterdam	Netherlands
5	University Medical Center St. Radboud	Nijmegen	Netherlands
6	Erasmus Medical Center	Rotterdam	Netherlands
7	University Medical Center Utrecht	Utrecht	Netherlands
8	HUMI Vall d'Hebron	Barcelona	Spain