Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study

S Spijkers; AS Littooij; TC Kwee; N Tolboom; Auke Beishuizen; MCA Bruin; SG Elias; T van de Brug; G Enríquez; C Sábado; E Miller; C Granata; C Lange; F Verzegnassi; ML Greer; B Keizer; RAJ Nievelstein

doi:10.1007/s00330-020-07182-0

Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study

S Spijkers, AS Littooij, TC Kwee, N Tolboom, Auke Beishuizen, MCA Bruin, SG Elias, T van de Brug, G Enríquez, C Sábado, E Miller, C Granata, C Lange, F Verzegnassi, ML Greer, B Keizer, RAJ Nievelstein

Pediatrics

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Abstract

Objectives: To assess the concordance of whole-body MRI (WB-MRI) and an FDG-PET/CT-based reference standard for the initial staging in children with Hodgkin lymphoma (HL) Methods: Children with newly diagnosed HL were included in this prospective, multicentre, international study and underwent WB-MRI and FDG-PET/CT at staging. Two radiologists and a nuclear medicine physician independently evaluated all images. Discrepancies between WB-MRI and FDG-PET/CT were assessed by an expert panel. All FDG-PET/CT errors were corrected to derive the FDG-PET/CT-based reference standard. The expert panel corrected all reader errors in the WB-MRI DWI dataset to form the intrinsic MRI data. Inter-observer agreement for WB-MRI DWI was calculated using overall agreement, specific agreements and kappa statistics. Concordance for correct classification of all disease sites and disease stage between WB-MRI (without DWI, with DWI and intrinsic WB-MRI DWI) and the reference standard was calculated as primary outcome. Secondary outcomes included positive predictive value, negative predictive value and kappa statistics. Clustering within patients was accounted for using a mixed-effect logistic regression model with random intercepts and a multilevel kappa analysis. Results: Sixty-eight children were included. Inter-observer agreement between WB-MRI DWI readers was good for disease stage (κ = 0.74). WB-MRI DWI agreed with the FDG-PET/CT-based reference standard for determining disease stage in 96% of the patients versus 88% for WB-MRI without DWI. Agreement between WB-MRI DWI and the reference standard was excellent for both nodal (98%) and extra-nodal (100%) staging. Conclusions: WB-MRI DWI showed excellent agreement with the FDG-PET/CT-based reference standard. The addition of DWI to the WB-MRI protocol improved the staging agreement. Key Points: • This study showed excellent agreement between WB-MRI DWI and an FDG-PET/CT-based reference standard for staging paediatric HL. • Diffusion-weighted imaging is a useful addition to WB-MRI in staging paediatric HL. • Inter-observer agreement for WB-MRI DWI was good for both nodal and extra-nodal staging and determining disease stage.

Original language	English
Pages (from-to)	1494-1504
Number of pages	11
Journal	European Radiology
Volume	31
Issue number	3
DOIs	https://doi.org/10.1007/s00330-020-07182-0
Publication status	Published - 2021

Bibliographical note

Funding Information:
This project was financially supported by Stichting Kinderen Kankervrij (KiKa, project number 87). The collection, analysis and interpretation of data, the writing of the paper and the decision to submit were not influenced by KiKa. Acknowledgements

Funding Information:
We would like to thank Cuno S.P.M. Uiterwaal (Julius Center for Health Sciences and Primary Care) and Marnix G.E.H. Lam (Radiology and Nuclear Medicine, University Medical Centre Utrecht) for their contribution to the study.

Publisher Copyright:
© 2020, The Author(s).

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Spijkers2021_Article_Whole-bodyMRIVersusAnFDG-PETCTFinal published version, 4.99 MBLicence: CC BY

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Spijkers, S., Littooij, AS., Kwee, TC., Tolboom, N., Beishuizen, A., Bruin, MCA., Elias, SG., van de Brug, T., Enríquez, G., Sábado, C., Miller, E., Granata, C., Lange, C., Verzegnassi, F., Greer, ML., Keizer, B., & Nievelstein, RAJ. (2021). Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study. European Radiology, 31(3), 1494-1504. https://doi.org/10.1007/s00330-020-07182-0

@article{cdfa54018e7248f6863d076bd402475a,

title = "Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study",

abstract = "Objectives: To assess the concordance of whole-body MRI (WB-MRI) and an FDG-PET/CT-based reference standard for the initial staging in children with Hodgkin lymphoma (HL) Methods: Children with newly diagnosed HL were included in this prospective, multicentre, international study and underwent WB-MRI and FDG-PET/CT at staging. Two radiologists and a nuclear medicine physician independently evaluated all images. Discrepancies between WB-MRI and FDG-PET/CT were assessed by an expert panel. All FDG-PET/CT errors were corrected to derive the FDG-PET/CT-based reference standard. The expert panel corrected all reader errors in the WB-MRI DWI dataset to form the intrinsic MRI data. Inter-observer agreement for WB-MRI DWI was calculated using overall agreement, specific agreements and kappa statistics. Concordance for correct classification of all disease sites and disease stage between WB-MRI (without DWI, with DWI and intrinsic WB-MRI DWI) and the reference standard was calculated as primary outcome. Secondary outcomes included positive predictive value, negative predictive value and kappa statistics. Clustering within patients was accounted for using a mixed-effect logistic regression model with random intercepts and a multilevel kappa analysis. Results: Sixty-eight children were included. Inter-observer agreement between WB-MRI DWI readers was good for disease stage (κ = 0.74). WB-MRI DWI agreed with the FDG-PET/CT-based reference standard for determining disease stage in 96% of the patients versus 88% for WB-MRI without DWI. Agreement between WB-MRI DWI and the reference standard was excellent for both nodal (98%) and extra-nodal (100%) staging. Conclusions: WB-MRI DWI showed excellent agreement with the FDG-PET/CT-based reference standard. The addition of DWI to the WB-MRI protocol improved the staging agreement. Key Points: • This study showed excellent agreement between WB-MRI DWI and an FDG-PET/CT-based reference standard for staging paediatric HL. • Diffusion-weighted imaging is a useful addition to WB-MRI in staging paediatric HL. • Inter-observer agreement for WB-MRI DWI was good for both nodal and extra-nodal staging and determining disease stage.",

author = "S Spijkers and AS Littooij and TC Kwee and N Tolboom and Auke Beishuizen and MCA Bruin and SG Elias and {van de Brug}, T and G Enr{\'i}quez and C S{\'a}bado and E Miller and C Granata and C Lange and F Verzegnassi and ML Greer and B Keizer and RAJ Nievelstein",

note = "Funding Information: This project was financially supported by Stichting Kinderen Kankervrij (KiKa, project number 87). The collection, analysis and interpretation of data, the writing of the paper and the decision to submit were not influenced by KiKa. Acknowledgements Funding Information: We would like to thank Cuno S.P.M. Uiterwaal (Julius Center for Health Sciences and Primary Care) and Marnix G.E.H. Lam (Radiology and Nuclear Medicine, University Medical Centre Utrecht) for their contribution to the study. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2021",

doi = "10.1007/s00330-020-07182-0",

language = "English",

volume = "31",

pages = "1494--1504",

journal = "European Radiology",

issn = "0938-7994",

publisher = "Springer-Verlag",

number = "3",

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Spijkers, S, Littooij, AS, Kwee, TC, Tolboom, N, Beishuizen, A, Bruin, MCA, Elias, SG, van de Brug, T, Enríquez, G, Sábado, C, Miller, E, Granata, C, Lange, C, Verzegnassi, F, Greer, ML, Keizer, B & Nievelstein, RAJ 2021, 'Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study', European Radiology, vol. 31, no. 3, pp. 1494-1504. https://doi.org/10.1007/s00330-020-07182-0

TY - JOUR

T1 - Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study

AU - Spijkers, S

AU - Littooij, AS

AU - Kwee, TC

AU - Tolboom, N

AU - Beishuizen, Auke

AU - Bruin, MCA

AU - Elias, SG

AU - van de Brug, T

AU - Enríquez, G

AU - Sábado, C

AU - Miller, E

AU - Granata, C

AU - Lange, C

AU - Verzegnassi, F

AU - Greer, ML

AU - Keizer, B

AU - Nievelstein, RAJ

N1 - Funding Information: This project was financially supported by Stichting Kinderen Kankervrij (KiKa, project number 87). The collection, analysis and interpretation of data, the writing of the paper and the decision to submit were not influenced by KiKa. Acknowledgements Funding Information: We would like to thank Cuno S.P.M. Uiterwaal (Julius Center for Health Sciences and Primary Care) and Marnix G.E.H. Lam (Radiology and Nuclear Medicine, University Medical Centre Utrecht) for their contribution to the study. Publisher Copyright: © 2020, The Author(s).

PY - 2021

Y1 - 2021

N2 - Objectives: To assess the concordance of whole-body MRI (WB-MRI) and an FDG-PET/CT-based reference standard for the initial staging in children with Hodgkin lymphoma (HL) Methods: Children with newly diagnosed HL were included in this prospective, multicentre, international study and underwent WB-MRI and FDG-PET/CT at staging. Two radiologists and a nuclear medicine physician independently evaluated all images. Discrepancies between WB-MRI and FDG-PET/CT were assessed by an expert panel. All FDG-PET/CT errors were corrected to derive the FDG-PET/CT-based reference standard. The expert panel corrected all reader errors in the WB-MRI DWI dataset to form the intrinsic MRI data. Inter-observer agreement for WB-MRI DWI was calculated using overall agreement, specific agreements and kappa statistics. Concordance for correct classification of all disease sites and disease stage between WB-MRI (without DWI, with DWI and intrinsic WB-MRI DWI) and the reference standard was calculated as primary outcome. Secondary outcomes included positive predictive value, negative predictive value and kappa statistics. Clustering within patients was accounted for using a mixed-effect logistic regression model with random intercepts and a multilevel kappa analysis. Results: Sixty-eight children were included. Inter-observer agreement between WB-MRI DWI readers was good for disease stage (κ = 0.74). WB-MRI DWI agreed with the FDG-PET/CT-based reference standard for determining disease stage in 96% of the patients versus 88% for WB-MRI without DWI. Agreement between WB-MRI DWI and the reference standard was excellent for both nodal (98%) and extra-nodal (100%) staging. Conclusions: WB-MRI DWI showed excellent agreement with the FDG-PET/CT-based reference standard. The addition of DWI to the WB-MRI protocol improved the staging agreement. Key Points: • This study showed excellent agreement between WB-MRI DWI and an FDG-PET/CT-based reference standard for staging paediatric HL. • Diffusion-weighted imaging is a useful addition to WB-MRI in staging paediatric HL. • Inter-observer agreement for WB-MRI DWI was good for both nodal and extra-nodal staging and determining disease stage.

AB - Objectives: To assess the concordance of whole-body MRI (WB-MRI) and an FDG-PET/CT-based reference standard for the initial staging in children with Hodgkin lymphoma (HL) Methods: Children with newly diagnosed HL were included in this prospective, multicentre, international study and underwent WB-MRI and FDG-PET/CT at staging. Two radiologists and a nuclear medicine physician independently evaluated all images. Discrepancies between WB-MRI and FDG-PET/CT were assessed by an expert panel. All FDG-PET/CT errors were corrected to derive the FDG-PET/CT-based reference standard. The expert panel corrected all reader errors in the WB-MRI DWI dataset to form the intrinsic MRI data. Inter-observer agreement for WB-MRI DWI was calculated using overall agreement, specific agreements and kappa statistics. Concordance for correct classification of all disease sites and disease stage between WB-MRI (without DWI, with DWI and intrinsic WB-MRI DWI) and the reference standard was calculated as primary outcome. Secondary outcomes included positive predictive value, negative predictive value and kappa statistics. Clustering within patients was accounted for using a mixed-effect logistic regression model with random intercepts and a multilevel kappa analysis. Results: Sixty-eight children were included. Inter-observer agreement between WB-MRI DWI readers was good for disease stage (κ = 0.74). WB-MRI DWI agreed with the FDG-PET/CT-based reference standard for determining disease stage in 96% of the patients versus 88% for WB-MRI without DWI. Agreement between WB-MRI DWI and the reference standard was excellent for both nodal (98%) and extra-nodal (100%) staging. Conclusions: WB-MRI DWI showed excellent agreement with the FDG-PET/CT-based reference standard. The addition of DWI to the WB-MRI protocol improved the staging agreement. Key Points: • This study showed excellent agreement between WB-MRI DWI and an FDG-PET/CT-based reference standard for staging paediatric HL. • Diffusion-weighted imaging is a useful addition to WB-MRI in staging paediatric HL. • Inter-observer agreement for WB-MRI DWI was good for both nodal and extra-nodal staging and determining disease stage.

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Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study

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