Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements

J J Eertink; A I J Arens; J E Huijbregts; F Celik; B de Keizer; S Stroobants; D de Jong; S E Wiegers; G J C Zwezerijnen; C N Burggraaff; R Boellaard; H C W de Vet; O S Hoekstra; P J Lugtenburg; M E D Chamuleau; J M Zijlstra; HOVON imaging workgroup

doi:10.1007/s00259-021-05498-7

Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements

Eur J Nucl Med Mol Imaging. 2022 Feb;49(3):943-952. doi: 10.1007/s00259-021-05498-7. Epub 2021 Sep 2.

Authors

J J Eertink¹, A I J Arens², J E Huijbregts³, F Celik⁴, B de Keizer⁵, S Stroobants⁶, D de Jong⁷, S E Wiegers¹, G J C Zwezerijnen⁸, C N Burggraaff¹, R Boellaard⁸, H C W de Vet⁹, O S Hoekstra⁸, P J Lugtenburg¹⁰, M E D Chamuleau¹, J M Zijlstra¹¹; HOVON imaging workgroup

Affiliations

¹ Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
² Department of Radiology, Nuclear Medicine and Anatomy, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands.
³ Department of Radiology and Nuclear Medicine, Gelre Ziekenhuizen, Albert Schweitzerlaan 31, Apeldoorn, The Netherlands.
⁴ Department of Radiology and Nuclear Medicine, Deventer Ziekenhuis, Nico Bolkesteinlaan 75, Deventer, The Netherlands.
⁵ Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
⁶ Department of Nuclear Medicine, Antwerp University Hospital (UZA), Antwerp, Belgium.
⁷ Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands.
⁸ Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands.
⁹ Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands.
¹⁰ Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Wytemaweg 80, Rotterdam, The Netherlands.
¹¹ Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. j.zijlstra@amsterdamumc.nl.

Abstract

Purpose: MYC gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in MYC + and MYC- DLBCL patients.

Methods: Interim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81 MYC + and 129 MYC- DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival.

Results: MYC + DLBCL patients had significantly more positive EoT-PET scans than MYC- patients (32.5 vs 15.7%, p = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In MYC + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the MYC- patients (p = 0.002). Nine (34.6%) MYC + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%) MYC- patient. A total of 80.8% of EoT-PET positive MYC + patients showed both increased lesional SUV and MTV compared to I-PET. In MYC- patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both MYC subgroups (81.8-94.1%). PPV was highest at EoT-PET for MYC + patients (61.5%).

Conclusion: MYC + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved.

Trial registration number and date of registration: HOVON-84: EudraCT: 2006-005,174-42, retrospectively registered 01-08-2008. HOVON-130: EudraCT: 2014-002,654-39, registered 26-01-2015.

Keywords: 18F FDG PET/CT; Deauville score; Diffuse large B-cell lymphoma; MYC rearrangement; Response.

MeSH terms

Fluorodeoxyglucose F18
Gene Rearrangement
Humans
Lymphoma, Large B-Cell, Diffuse* / diagnostic imaging
Lymphoma, Large B-Cell, Diffuse* / genetics
Lymphoma, Large B-Cell, Diffuse* / therapy
Positron Emission Tomography Computed Tomography* / methods
Positron-Emission Tomography
Prognosis
Retrospective Studies

Substances

Fluorodeoxyglucose F18