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出境医 / 临床实验 / Whole-body MRI in Pediatric Hodgkin's Lymphoma

Whole-body MRI in Pediatric Hodgkin's Lymphoma

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
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:

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.

Study Design
Layout table for study information
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 : June 2011
Actual Primary Completion Date : December 2016
Actual Study Completion Date : September 2020
Arms and Interventions
Group/Cohort
Pediatric Hodgkin's lymphoma
Children with newly diagnosed Hodgkin's lymphoma
Outcome Measures
Primary Outcome Measures :
  1. Staging (Ann Arbor) [ Time Frame: 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.

  2. Early treatment response assessment (Cheson criteria) [ Time Frame: 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.

  3. Restaging at end of therapy (Cheson criteria) [ Time Frame: 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.

  4. Follow up for 3 years after end of treatment [ Time Frame: 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 :
  1. Image quality [ Time Frame: 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.

  2. Interobserver variability of WB-MRI for staging, early response assessment and restaging at end of therapy [ Time Frame: 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
Layout table for eligibility information
Ages Eligible for Study:   8 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients, aged 8-18 years, with newly diagnosed Hodgkin's lymphoma, who will undergo PET/CT for staging, early response assessment and restaging at completion of therapy (imaging standards according to the Euronet-PHL-C1 protocol).
Criteria

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
Layout table for location information
Austria
LKH-Universitätsklinikum Graz
Graz, Austria
Italy
Ospedale Giannina Gaslini
Genova, Italy
Netherlands
Academic Medical Center Amsterdam
Amsterdam, Netherlands
VU University Medical Center
Amsterdam, Netherlands
University Medical Center St. Radboud
Nijmegen, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
University Medical Center Utrecht
Utrecht, Netherlands
Spain
HUMI Vall d'Hebron
Barcelona, Spain
Sponsors and Collaborators
UMC Utrecht
Stichting Kinderen Kankervrij (KiKa)
Investigators
Layout table for investigator information
Principal Investigator: Rutger AJ Nievelstein, MD PhD UMC Utrecht
Tracking Information
First Submitted Date July 2, 2013
First Posted Date July 2, 2019
Last Update Posted Date November 3, 2020
Actual Study Start Date June 2011
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 16, 2019)
  • Staging (Ann Arbor) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures
 (submitted: July 1, 2019)
  • Staging (Ann Arbor) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 3 years ]
    To determine the percentage of relapse of Hodgkin lymphoma in this study cohort, and the percentage of true- versus false-positives on WB-MRI at end of treatment compared to PET/CT using follow-up.
Change History
Current Secondary Outcome Measures
 (submitted: July 16, 2019)
  • Image quality [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures
 (submitted: July 1, 2019)
  • Image quality [ Time Frame: 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 [ Time Frame: Day 1, 2 months, 6 months ]
    To determine the interobserver variability of WB-MRI (including DWIBS) for staging, early response assessment and restaging at end of therapy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Whole-body MRI in Pediatric Hodgkin's Lymphoma
Official Title Whole-body MRI for Initial Staging, Early Response Assessment and Restaging After Completion of Therapy in Pediatric Hodgkin's Lymphoma.
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.

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:

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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients, aged 8-18 years, with newly diagnosed Hodgkin's lymphoma, who will undergo PET/CT for staging, early response assessment and restaging at completion of therapy (imaging standards according to the Euronet-PHL-C1 protocol).
Condition Hodgkin's Lymphoma
Intervention Not Provided
Study Groups/Cohorts Pediatric Hodgkin's lymphoma
Children with newly diagnosed Hodgkin's lymphoma
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 1, 2019)
75
Original Actual Enrollment Same as current
Actual Study Completion Date September 2020
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 8 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Austria,   Italy,   Netherlands,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number NCT04005703
Other Study ID Numbers KIKA project number 87
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party R.A.J. Nievelstein, UMC Utrecht
Study Sponsor UMC Utrecht
Collaborators Stichting Kinderen Kankervrij (KiKa)
Investigators
Principal Investigator: Rutger AJ Nievelstein, MD PhD UMC Utrecht
PRS Account UMC Utrecht
Verification Date November 2020

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