Ionising radiation-free whole-body MRI versus 18F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: A prospective, non-randomised, single-centre study

Christopher Klenk; Rakhee Gawande; Lebriz Uslu; Aman Khurana; Deqiang Qiu; Andrew Quon; Jessica Donig; Jarrett Rosenberg; Sandra Luna-Fineman; Michael Moseley; Heike E. Daldrup-Link

doi:10.1016/S1470-2045(14)70021-X

Ionising radiation-free whole-body MRI versus ¹⁸F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: A prospective, non-randomised, single-centre study

Christopher Klenk, Rakhee Gawande, Lebriz Uslu, Aman Khurana, Deqiang Qiu, Andrew Quon, Jessica Donig, Jarrett Rosenberg, Sandra Luna-Fineman, Michael Moseley, Heike E. Daldrup-Link

Radiology

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

Abstract

Background: Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent. Methods: We compared whole-body diffusion-weighted MRI with standard clinical ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated ¹⁸F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879. Findings: 22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for ¹⁸F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. ¹⁸F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing ¹⁸F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded. Interpretation: Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to ¹⁸F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures. Funding: Thrasher Research Fund and Clinical Health Research Institute at Stanford University.

Original language	English (US)
Pages (from-to)	275-285
Number of pages	11
Journal	The Lancet Oncology
Volume	15
Issue number	3
DOIs	https://doi.org/10.1016/S1470-2045(14)70021-X
State	Published - Mar 2014

Bibliographical note

Funding Information:
We thank Sandy Napel and Daniel Owen for their valuable input and help with magnetic resonance image data fusion. We thank Karla and Kevin Epperson and Anne Saywer at the Richard M Lucas Center for their expert help with the whole-body MRI scans. We thank Jia Wang for his assistance regarding radiation dose calculations. LU was supported as a visiting scholar by the Scientific and Technological Research Council of Turkey (TÜBİTAK).

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Klenk, C., Gawande, R., Uslu, L., Khurana, A., Qiu, D., Quon, A., Donig, J., Rosenberg, J., Luna-Fineman, S., Moseley, M., & Daldrup-Link, H. E. (2014). Ionising radiation-free whole-body MRI versus ¹⁸F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: A prospective, non-randomised, single-centre study. The Lancet Oncology, 15(3), 275-285. https://doi.org/10.1016/S1470-2045(14)70021-X

Ionising radiation-free whole-body MRI versus ¹⁸F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer : A prospective, non-randomised, single-centre study. / Klenk, Christopher; Gawande, Rakhee; Uslu, Lebriz; Khurana, Aman; Qiu, Deqiang; Quon, Andrew; Donig, Jessica; Rosenberg, Jarrett; Luna-Fineman, Sandra; Moseley, Michael; Daldrup-Link, Heike E.

In: The Lancet Oncology, Vol. 15, No. 3, 03.2014, p. 275-285.

Research output: Contribution to journal › Article › peer-review

Klenk, C, Gawande, R, Uslu, L, Khurana, A, Qiu, D, Quon, A, Donig, J, Rosenberg, J, Luna-Fineman, S, Moseley, M & Daldrup-Link, HE 2014, 'Ionising radiation-free whole-body MRI versus ¹⁸F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: A prospective, non-randomised, single-centre study', The Lancet Oncology, vol. 15, no. 3, pp. 275-285. https://doi.org/10.1016/S1470-2045(14)70021-X

Klenk, Christopher ; Gawande, Rakhee ; Uslu, Lebriz ; Khurana, Aman ; Qiu, Deqiang ; Quon, Andrew ; Donig, Jessica ; Rosenberg, Jarrett ; Luna-Fineman, Sandra ; Moseley, Michael ; Daldrup-Link, Heike E. / Ionising radiation-free whole-body MRI versus ¹⁸F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer : A prospective, non-randomised, single-centre study. In: The Lancet Oncology. 2014 ; Vol. 15, No. 3. pp. 275-285.

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title = "Ionising radiation-free whole-body MRI versus 18F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: A prospective, non-randomised, single-centre study",

abstract = "Background: Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent. Methods: We compared whole-body diffusion-weighted MRI with standard clinical 18F-fluorodeoxyglucose (18F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated 18F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879. Findings: 22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for 18F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. 18F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing 18F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded. Interpretation: Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to 18F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures. Funding: Thrasher Research Fund and Clinical Health Research Institute at Stanford University.",

author = "Christopher Klenk and Rakhee Gawande and Lebriz Uslu and Aman Khurana and Deqiang Qiu and Andrew Quon and Jessica Donig and Jarrett Rosenberg and Sandra Luna-Fineman and Michael Moseley and Daldrup-Link, {Heike E.}",

note = "Funding Information: We thank Sandy Napel and Daniel Owen for their valuable input and help with magnetic resonance image data fusion. We thank Karla and Kevin Epperson and Anne Saywer at the Richard M Lucas Center for their expert help with the whole-body MRI scans. We thank Jia Wang for his assistance regarding radiation dose calculations. LU was supported as a visiting scholar by the Scientific and Technological Research Council of Turkey (T{\"U}BİTAK). ",

year = "2014",

month = mar,

doi = "10.1016/S1470-2045(14)70021-X",

language = "English (US)",

volume = "15",

pages = "275--285",

journal = "The Lancet Oncology",

issn = "1470-2045",

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TY - JOUR

T1 - Ionising radiation-free whole-body MRI versus 18F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer

T2 - A prospective, non-randomised, single-centre study

AU - Klenk, Christopher

AU - Gawande, Rakhee

AU - Uslu, Lebriz

AU - Khurana, Aman

AU - Qiu, Deqiang

AU - Quon, Andrew

AU - Donig, Jessica

AU - Rosenberg, Jarrett

AU - Luna-Fineman, Sandra

AU - Moseley, Michael

AU - Daldrup-Link, Heike E.

N1 - Funding Information: We thank Sandy Napel and Daniel Owen for their valuable input and help with magnetic resonance image data fusion. We thank Karla and Kevin Epperson and Anne Saywer at the Richard M Lucas Center for their expert help with the whole-body MRI scans. We thank Jia Wang for his assistance regarding radiation dose calculations. LU was supported as a visiting scholar by the Scientific and Technological Research Council of Turkey (TÜBİTAK).

PY - 2014/3

Y1 - 2014/3

N2 - Background: Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent. Methods: We compared whole-body diffusion-weighted MRI with standard clinical 18F-fluorodeoxyglucose (18F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated 18F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879. Findings: 22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for 18F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. 18F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing 18F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded. Interpretation: Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to 18F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures. Funding: Thrasher Research Fund and Clinical Health Research Institute at Stanford University.

AB - Background: Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent. Methods: We compared whole-body diffusion-weighted MRI with standard clinical 18F-fluorodeoxyglucose (18F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated 18F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879. Findings: 22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for 18F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. 18F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing 18F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded. Interpretation: Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to 18F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures. Funding: Thrasher Research Fund and Clinical Health Research Institute at Stanford University.

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