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Published in: European Radiology 1/2019

Open Access 01-01-2019 | Magnetic Resonance

Whole-body MRI for staging and interim response monitoring in paediatric and adolescent Hodgkin’s lymphoma: a comparison with multi-modality reference standard including 18F-FDG-PET-CT

Authors: Arash Latifoltojar, Shonit Punwani, Andre Lopes, Paul D. Humphries, Maria Klusmann, Leon Jonathan Menezes, Stephen Daw, Ananth Shankar, Deena Neriman, Heather Fitzke, Laura Clifton-Hadley, Paul Smith, Stuart A. Taylor

Published in: European Radiology | Issue 1/2019

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Abstract

Objectives

To prospectively investigate concordance between whole-body MRI (WB-MRI) and a composite reference standard for initial staging and interim response evaluation in paediatric and adolescent Hodgkin’s lymphoma.

Methods

Fifty patients (32 male, age range 6–19 years) underwent WB-MRI and standard investigations, including 18F-FDG-PET-CT at diagnosis and following 2–3 chemotherapy cycles. Two radiologists in consensus interpreted WB-MRI using prespecified definitions of disease positivity. A third radiologist reviewed a subset of staging WB-MRIs (n = 38) separately to test for interobserver agreement. A multidisciplinary team derived a primary reference standard using all available imaging/clinical investigations. Subsequently, a second multidisciplinary panel rereviewed all imaging with long-term follow-up data to derive an enhanced reference standard. Interobserver agreement for WB-MRI reads was tested using kappa statistics. Concordance for correct classification of all disease sites, true positive rate (TPR), false positive rate (FPR) and kappa for staging/response agreement were calculated for WB-MRI.

Results

There was discordance for full stage in 74% (95% CI 61.9–83.9%) and 44% (32.0–56.6%) of patients against the primary and enhanced reference standards, respectively. Against the enhanced reference standard, the WB-MRI TPR, FPR and kappa were 91%, 1% and 0.93 (0.90–0.96) for nodal disease and 79%, < 1% and 0.86 (0.77–0.95) for extra-nodal disease. WB-MRI response classification was correct in 25/38 evaluable patients (66%), underestimating response in 26% (kappa 0.30, 95% CI 0.04–0.57). There was a good agreement for nodal (kappa 0.78, 95% CI 0.73–0.84) and extra-nodal staging (kappa 0.60, 95% CI 0.41–0.78) between WB-MRI reads

Conclusions

WB-MRI has reasonable accuracy for nodal and extra-nodal staging but is discordant with standard imaging in a substantial minority of patients, and tends to underestimate disease response.

Key Points

• This prospective single-centre study showed discordance for full patient staging of 44% between WB-MRI and a multi-modality reference standard in paediatric and adolescent Hodgkin’s lymphoma.
• WB-MRI underestimates interim disease response in paediatric and adolescent Hodgkin’s lymphoma.
• WB-MRI shows promise in paediatric and adolescent Hodgkin’s lymphoma but currently cannot replace conventional staging pathways including 18F-FDG-PET-CT.
Appendix
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Literature
1.
go back to reference Ward E, DeSantis C, Robbins A, Kohler B, Jemal A (2014) Childhood and adolescent cancer statistics. CA Cancer J Clin 64:83–103CrossRef Ward E, DeSantis C, Robbins A, Kohler B, Jemal A (2014) Childhood and adolescent cancer statistics. CA Cancer J Clin 64:83–103CrossRef
2.
go back to reference Uslu L, Doing J, Link M, Rosenberg J, Quon A, Daldrup-Link HE (2015) Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies. J Nucl Med 56:274–286CrossRef Uslu L, Doing J, Link M, Rosenberg J, Quon A, Daldrup-Link HE (2015) Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies. J Nucl Med 56:274–286CrossRef
3.
go back to reference Wahl RL, Jacene H, Kasamon Y, Lodge MA (2009) From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med 50(Suppl 1):122S–150SCrossRef Wahl RL, Jacene H, Kasamon Y, Lodge MA (2009) From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med 50(Suppl 1):122S–150SCrossRef
4.
go back to reference Cheson BD, Fisher RI, Barrington SF et al (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32:3059–3068CrossRef Cheson BD, Fisher RI, Barrington SF et al (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32:3059–3068CrossRef
5.
go back to reference Hall EJ, Brenner DJ (2008) Cancer risks from diagnostic radiology. Br J Radiol 81:362–378CrossRef Hall EJ, Brenner DJ (2008) Cancer risks from diagnostic radiology. Br J Radiol 81:362–378CrossRef
6.
go back to reference Nievelstein RA, Littooij AS (2016) Whole-body MRI in paediatric oncology. Radiol Med 121:442–453CrossRef Nievelstein RA, Littooij AS (2016) Whole-body MRI in paediatric oncology. Radiol Med 121:442–453CrossRef
7.
go back to reference Brenner D, Elliston C, Hall E, Berdon W (2001) Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR Am J Roentgenol 176:289–296CrossRef Brenner D, Elliston C, Hall E, Berdon W (2001) Estimated risks of radiation-induced fatal cancer from pediatric CT. AJR Am J Roentgenol 176:289–296CrossRef
8.
go back to reference Davis JT, Kwatra N, Schooler GR (2016) Pediatric whole-body MRI: a review of current imaging techniques and clinical applications. J Magn Reson Imaging 44:783–793CrossRef Davis JT, Kwatra N, Schooler GR (2016) Pediatric whole-body MRI: a review of current imaging techniques and clinical applications. J Magn Reson Imaging 44:783–793CrossRef
9.
go back to reference Greer MC, Voss SD, States LJ (2017) Pediatric cancer predisposition imaging: focus on whole-body MRI. Clin Cancer Res 23:e6–e13CrossRef Greer MC, Voss SD, States LJ (2017) Pediatric cancer predisposition imaging: focus on whole-body MRI. Clin Cancer Res 23:e6–e13CrossRef
10.
go back to reference Maggialetti N, Ferrari C, Minoia C et al (2016) Role of WB-MR/DWIBS compared to (18)F-FDG PET/CT in the therapy response assessment of lymphoma. Radiol Med 121:132–143CrossRef Maggialetti N, Ferrari C, Minoia C et al (2016) Role of WB-MR/DWIBS compared to (18)F-FDG PET/CT in the therapy response assessment of lymphoma. Radiol Med 121:132–143CrossRef
11.
go back to reference Tsuji K, Kishi S, Tsuchida T et al (2015) Evaluation of staging and early response to chemotherapy with whole-body diffusion-weighted MRI in malignant lymphoma patients: A comparison with FDG-PET/CT. J Magn Reson Imaging 41:1601–1607CrossRef Tsuji K, Kishi S, Tsuchida T et al (2015) Evaluation of staging and early response to chemotherapy with whole-body diffusion-weighted MRI in malignant lymphoma patients: A comparison with FDG-PET/CT. J Magn Reson Imaging 41:1601–1607CrossRef
12.
go back to reference Punwani S, Taylor SA, Saad ZZ et al (2013) Diffusion-weighted MRI of lymphoma: prognostic utility and implication for PET/MRI? Eur J Nucl Med Mol Imaging 40:373–385CrossRef Punwani S, Taylor SA, Saad ZZ et al (2013) Diffusion-weighted MRI of lymphoma: prognostic utility and implication for PET/MRI? Eur J Nucl Med Mol Imaging 40:373–385CrossRef
13.
go back to reference Littooij AS, Kwee TC, de Keizer B et al (2015) Whole-body MRI-DWI for assessment of residual disease after completion of therapy in lymphoma: a prospective multicenter study. J Magn Reson Imaging 42:1646–1655CrossRef Littooij AS, Kwee TC, de Keizer B et al (2015) Whole-body MRI-DWI for assessment of residual disease after completion of therapy in lymphoma: a prospective multicenter study. J Magn Reson Imaging 42:1646–1655CrossRef
14.
go back to reference Punwani S, Taylor SA, Bainbridge A et al (2010) Pediatric and adolescent lymphoma: comparison of whole-body STIR half-Fourier RARE MR imaging with an enhanced PET/CT reference for initial staging. Radiology 255:182–190CrossRef Punwani S, Taylor SA, Bainbridge A et al (2010) Pediatric and adolescent lymphoma: comparison of whole-body STIR half-Fourier RARE MR imaging with an enhanced PET/CT reference for initial staging. Radiology 255:182–190CrossRef
15.
go back to reference Kwee TC, Vermoolen MA, Akkerman EA et al (2014) Whole-body MRI, including diffusion-weighted imaging, for staging lymphoma: comparison with CT in a prospective multicenter study. J Magn Reson Imaging 40:26–36CrossRef Kwee TC, Vermoolen MA, Akkerman EA et al (2014) Whole-body MRI, including diffusion-weighted imaging, for staging lymphoma: comparison with CT in a prospective multicenter study. J Magn Reson Imaging 40:26–36CrossRef
16.
go back to reference Regacini R, Puchnick A, Shigueoka DC, Iared W, Lederman HM (2015) Whole-body diffusion-weighted magnetic resonance imaging versus FDG-PET/CT for initial lymphoma staging: systematic review on diagnostic test accuracy studies. Sao Paulo Med J 133:141–150CrossRef Regacini R, Puchnick A, Shigueoka DC, Iared W, Lederman HM (2015) Whole-body diffusion-weighted magnetic resonance imaging versus FDG-PET/CT for initial lymphoma staging: systematic review on diagnostic test accuracy studies. Sao Paulo Med J 133:141–150CrossRef
17.
go back to reference Mayerhoefer ME, Karanikas G, Kletter K et al (2014) Evaluation of diffusion-weighted MRI for pretherapeutic assessment and staging of lymphoma: results of a prospective study in 140 patients. Clin Cancer Res 20:2984–2993CrossRef Mayerhoefer ME, Karanikas G, Kletter K et al (2014) Evaluation of diffusion-weighted MRI for pretherapeutic assessment and staging of lymphoma: results of a prospective study in 140 patients. Clin Cancer Res 20:2984–2993CrossRef
18.
go back to reference Mayerhoefer ME, Karanikas G, Kletter K et al (2015) Evaluation of diffusion-weighted magnetic resonance imaging for follow-up and treatment response assessment of lymphoma: results of an 18F-FDG-PET/CT-controlled prospective study in 64 patients. Clin Cancer Res 21:2506–2513CrossRef Mayerhoefer ME, Karanikas G, Kletter K et al (2015) Evaluation of diffusion-weighted magnetic resonance imaging for follow-up and treatment response assessment of lymphoma: results of an 18F-FDG-PET/CT-controlled prospective study in 64 patients. Clin Cancer Res 21:2506–2513CrossRef
19.
go back to reference Littooij AS, Kwee TC, Barber I et al (2014) Whole-body MRI for initial staging of paediatric lymphoma: prospective comparison to an FDG-PET/CT-based reference standard. Eur Radiol 24:1153–1165CrossRef Littooij AS, Kwee TC, Barber I et al (2014) Whole-body MRI for initial staging of paediatric lymphoma: prospective comparison to an FDG-PET/CT-based reference standard. Eur Radiol 24:1153–1165CrossRef
21.
go back to reference Punwani S, Prakash V, Bainbridge A et al (2010) Quantitative diffusion weighted MRI: a functional biomarker of nodal disease in Hodgkin’s lymphoma. Cancer Biomarker 7:249–259CrossRef Punwani S, Prakash V, Bainbridge A et al (2010) Quantitative diffusion weighted MRI: a functional biomarker of nodal disease in Hodgkin’s lymphoma. Cancer Biomarker 7:249–259CrossRef
22.
go back to reference Eich HT, Diehl V, Görgen H et al (2010) Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol 28:4199–4206CrossRef Eich HT, Diehl V, Görgen H et al (2010) Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol 28:4199–4206CrossRef
23.
go back to reference Vandecaveye V, De Keyzer F, Vander Poorten V et al (2009) Head and neck squamous cell carcinoma: value of diffusion-weighted MR imaging for nodal staging. Radiology 251:134–146CrossRef Vandecaveye V, De Keyzer F, Vander Poorten V et al (2009) Head and neck squamous cell carcinoma: value of diffusion-weighted MR imaging for nodal staging. Radiology 251:134–146CrossRef
24.
go back to reference Afaq A, Fraioli F, Sidhu H et al (2017) Comparison of PET/MRI with PET/CT in the evaluation of disease status in lymphoma. Clin Nucl Med 42:e1–e7CrossRef Afaq A, Fraioli F, Sidhu H et al (2017) Comparison of PET/MRI with PET/CT in the evaluation of disease status in lymphoma. Clin Nucl Med 42:e1–e7CrossRef
25.
go back to reference Hagtvedt T, Seierstad T, Lund KV et al (2015) Diffusion-weighted MRI compared to FDG PET/CT for assessment of early treatment response in lymphoma. Acta Radiol 56:152–158CrossRef Hagtvedt T, Seierstad T, Lund KV et al (2015) Diffusion-weighted MRI compared to FDG PET/CT for assessment of early treatment response in lymphoma. Acta Radiol 56:152–158CrossRef
26.
go back to reference Padhani AR, Koh DM, Collins DJ (2011) Whole-body diffusion-weighted MR imaging in cancer: current status and research directions. Radiology 261:700–718CrossRef Padhani AR, Koh DM, Collins DJ (2011) Whole-body diffusion-weighted MR imaging in cancer: current status and research directions. Radiology 261:700–718CrossRef
27.
go back to reference Latifoltojar A, Hall-Craggs M, Bainbridge A et al (2017) Whole-body MRI quantitative biomarkers are associated significantly with treatment response in patients with newly diagnosed symptomatic multiple myeloma following bortezomib induction. Eur Radiol 27:5325–5336CrossRef Latifoltojar A, Hall-Craggs M, Bainbridge A et al (2017) Whole-body MRI quantitative biomarkers are associated significantly with treatment response in patients with newly diagnosed symptomatic multiple myeloma following bortezomib induction. Eur Radiol 27:5325–5336CrossRef
28.
go back to reference Kohn MA, Carpenter CR, Newman TB (2013) Understanding the direction of bias in studies of diagnostic test accuracy. Acad Emerg Med 20:1194–1206CrossRef Kohn MA, Carpenter CR, Newman TB (2013) Understanding the direction of bias in studies of diagnostic test accuracy. Acad Emerg Med 20:1194–1206CrossRef
29.
go back to reference Barnes A, Alonzi R, Blackledge M et al (2018) UK quantitative WB-DWI technical workgroup: consensus meeting recommendations on optimisation, quality control, processing and analysis of quantitative whole-body diffusion-weighted imaging for cancer. Br J Radiol. https://doi.org/10.1259/bjr.20170577 Barnes A, Alonzi R, Blackledge M et al (2018) UK quantitative WB-DWI technical workgroup: consensus meeting recommendations on optimisation, quality control, processing and analysis of quantitative whole-body diffusion-weighted imaging for cancer. Br J Radiol. https://​doi.​org/​10.​1259/​bjr.​20170577
30.
go back to reference Celik A (2016) Effect of imaging parameters on the accuracy of apparent diffusion coefficient and optimization strategy. Diagn Interv Radiol 22:101–107CrossRef Celik A (2016) Effect of imaging parameters on the accuracy of apparent diffusion coefficient and optimization strategy. Diagn Interv Radiol 22:101–107CrossRef
31.
go back to reference Koh DM, Collins DJ, Orton MR (2011) Intravoxel incoherent motion in body diffusion-weighted MRI: reality and challenges. AJR Am J Roentgenol 196:1351–1361CrossRef Koh DM, Collins DJ, Orton MR (2011) Intravoxel incoherent motion in body diffusion-weighted MRI: reality and challenges. AJR Am J Roentgenol 196:1351–1361CrossRef
32.
go back to reference Bankier AA, Levine D, Halpern EF, Kressel HY (2010) Consensus interpretation in imaging research: is there a better way? Radiology 257:14–17CrossRef Bankier AA, Levine D, Halpern EF, Kressel HY (2010) Consensus interpretation in imaging research: is there a better way? Radiology 257:14–17CrossRef
33.
go back to reference Horger M, Claussen C, Kramer U, Fenchel M, Linchy M, Kaufmann S (2014) Very early indicators of response to systemic therapy in lymphoma patients based on alterations in water diffusivity—a preliminary experience in 20 patients undergoing whole-body diffusion-weighted imaging. Eur J Radiol 83:1655–1664CrossRef Horger M, Claussen C, Kramer U, Fenchel M, Linchy M, Kaufmann S (2014) Very early indicators of response to systemic therapy in lymphoma patients based on alterations in water diffusivity—a preliminary experience in 20 patients undergoing whole-body diffusion-weighted imaging. Eur J Radiol 83:1655–1664CrossRef
34.
go back to reference Furth C, Steffen IG, Amthauer H et al (2009) Early and late therapy response assessment with [18F]fluorodeoxyglucose positron emission tomography in pediatric Hodgkin's and adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma: analysis of a prospective multicenter trial. J Clin Oncol 27:4385–4391CrossRef Furth C, Steffen IG, Amthauer H et al (2009) Early and late therapy response assessment with [18F]fluorodeoxyglucose positron emission tomography in pediatric Hodgkin's and adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma: analysis of a prospective multicenter trial. J Clin Oncol 27:4385–4391CrossRef
35.
go back to reference Johnson P, Federico M, Kirkwood A et al (2016) Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med 374:2419–2429CrossRef Johnson P, Federico M, Kirkwood A et al (2016) Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med 374:2419–2429CrossRef
Metadata
Title
Whole-body MRI for staging and interim response monitoring in paediatric and adolescent Hodgkin’s lymphoma: a comparison with multi-modality reference standard including 18F-FDG-PET-CT
Authors
Arash Latifoltojar
Shonit Punwani
Andre Lopes
Paul D. Humphries
Maria Klusmann
Leon Jonathan Menezes
Stephen Daw
Ananth Shankar
Deena Neriman
Heather Fitzke
Laura Clifton-Hadley
Paul Smith
Stuart A. Taylor
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 1/2019
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-018-5445-8

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