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

doi:10.1007/s00259-021-05498-7

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^*

^*Corresponding author for this work

Hematology

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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.

Original language	English
Pages (from-to)	943-952
Number of pages	10
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	49
Issue number	3
DOIs	https://doi.org/10.1007/s00259-021-05498-7
Publication status	Published - Feb 2022

Bibliographical note

on behalf of the HOVON imaging workgroup

Previously presented at the 33rd Annual Congress of the European Association of Nuclear Medicine – EANM’20 Virtual in the top rated oral presentation (TROP) Session: PET for Haematological Tumours

Funding Information:
This work is financially supported by the Dutch Cancer Society (# VU 2018–11648).

Funding Information:
J.J.E., A.I.J.A., J.E.H., F.C., B.d.K., S.S., D.d.J., S.E.W., G.J.C.Z., C.N.B. H.C.W.d.V., O.S.H., and R.B. declare no competing financial interests. P.J.L. received research funding from Takeda, Servier, and Roche and received honoraria for advisory boards from Takeda, Servier, Genentech, Genmab, Celgene, and Incyte. M.E.D.C. received research funding from Genmab, Gilead, Celgene, and BMS and received honoraria for advisory boards from Abbvie. J.M.Z. received research funding from Roche and received honoraria for advisory boards from Takeda, Gilead, and Roche.

Publisher Copyright:
© 2021, The Author(s).

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Eertink, J. J., Arens, A. I. J., Huijbregts, J. E., Celik, F., de Keizer, B., Stroobants, S., de Jong, D., Wiegers, S. E., Zwezerijnen, G. J. C., Burggraaff, C. N., Boellaard, R., de Vet, H. C. W., Hoekstra, O. S., Lugtenburg, P. J., Chamuleau, M. E. D., & Zijlstra, J. M. (2022). Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements. European Journal of Nuclear Medicine and Molecular Imaging, 49(3), 943-952. https://doi.org/10.1007/s00259-021-05498-7

@article{3e863ea7805248798bb77bb911c347f8,

title = "Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements",

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. ",

author = "Eertink, {J. J.} and Arens, {A. I.J.} and Huijbregts, {J. E.} and F. Celik and {de Keizer}, B. and S. Stroobants and {de Jong}, D. and Wiegers, {S. E.} and Zwezerijnen, {G. J.C.} and Burggraaff, {C. N.} and R. Boellaard and {de Vet}, {H. C.W.} and Hoekstra, {O. S.} and Lugtenburg, {P. J.} and Chamuleau, {M. E.D.} and Zijlstra, {J. M.}",

note = "on behalf of the HOVON imaging workgroup Previously presented at the 33rd Annual Congress of the European Association of Nuclear Medicine – EANM{\textquoteright}20 Virtual in the top rated oral presentation (TROP) Session: PET for Haematological Tumours Funding Information: This work is financially supported by the Dutch Cancer Society (# VU 2018–11648). Funding Information: J.J.E., A.I.J.A., J.E.H., F.C., B.d.K., S.S., D.d.J., S.E.W., G.J.C.Z., C.N.B. H.C.W.d.V., O.S.H., and R.B. declare no competing financial interests. P.J.L. received research funding from Takeda, Servier, and Roche and received honoraria for advisory boards from Takeda, Servier, Genentech, Genmab, Celgene, and Incyte. M.E.D.C. received research funding from Genmab, Gilead, Celgene, and BMS and received honoraria for advisory boards from Abbvie. J.M.Z. received research funding from Roche and received honoraria for advisory boards from Takeda, Gilead, and Roche. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = feb,

doi = "10.1007/s00259-021-05498-7",

language = "English",

volume = "49",

pages = "943--952",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer-Verlag",

number = "3",

}

Eertink, JJ, Arens, AIJ, Huijbregts, JE, Celik, F, de Keizer, B, Stroobants, S, de Jong, D, Wiegers, SE, Zwezerijnen, GJC, Burggraaff, CN, Boellaard, R, de Vet, HCW, Hoekstra, OS, Lugtenburg, PJ, Chamuleau, MED & Zijlstra, JM 2022, 'Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements', European Journal of Nuclear Medicine and Molecular Imaging, vol. 49, no. 3, pp. 943-952. https://doi.org/10.1007/s00259-021-05498-7

TY - JOUR

T1 - Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements

AU - Eertink, J. J.

AU - Arens, A. I.J.

AU - Huijbregts, J. E.

AU - Celik, F.

AU - de Keizer, B.

AU - Stroobants, S.

AU - de Jong, D.

AU - Wiegers, S. E.

AU - Zwezerijnen, G. J.C.

AU - Burggraaff, C. N.

AU - Boellaard, R.

AU - de Vet, H. C.W.

AU - Hoekstra, O. S.

AU - Lugtenburg, P. J.

AU - Chamuleau, M. E.D.

AU - Zijlstra, J. M.

N1 - on behalf of the HOVON imaging workgroup Previously presented at the 33rd Annual Congress of the European Association of Nuclear Medicine – EANM’20 Virtual in the top rated oral presentation (TROP) Session: PET for Haematological Tumours Funding Information: This work is financially supported by the Dutch Cancer Society (# VU 2018–11648). Funding Information: J.J.E., A.I.J.A., J.E.H., F.C., B.d.K., S.S., D.d.J., S.E.W., G.J.C.Z., C.N.B. H.C.W.d.V., O.S.H., and R.B. declare no competing financial interests. P.J.L. received research funding from Takeda, Servier, and Roche and received honoraria for advisory boards from Takeda, Servier, Genentech, Genmab, Celgene, and Incyte. M.E.D.C. received research funding from Genmab, Gilead, Celgene, and BMS and received honoraria for advisory boards from Abbvie. J.M.Z. received research funding from Roche and received honoraria for advisory boards from Takeda, Gilead, and Roche. Publisher Copyright: © 2021, The Author(s).

PY - 2022/2

Y1 - 2022/2

N2 - 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.

AB - 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.

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U2 - 10.1007/s00259-021-05498-7

DO - 10.1007/s00259-021-05498-7

M3 - Article

C2 - 34476551

AN - SCOPUS:85114351919

SN - 1619-7070

VL - 49

SP - 943

EP - 952

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

IS - 3

ER -

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

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