Purpose

In lymphoma, [18]FDG-PET is well established for staging and end-of-therapy response assessment. A promising more recent application is ‘early response assessment’, meaning that response to treatment is predicted using interim PET (i-PET), i.e. PET during treatment. Timely assessment of forthcoming therapy failure in individual patients would have a profound impact on patient care by avoiding unnecessary toxicity and timely switching to potentially curative alternatives. Several observational studies have indicated that i-PET may be effective in early response prediction, but inconsistencies prevail, especially in non-Hodgkin’s lymphoma (NHL) including diffuse large B-cell lymphoma (DLBCL). It is unclear to which extent these are due to differences in the timing of PET during therapy, different PET positivity criteria, different therapies and/or different subtypes of lymphoma. There is an urgent need to address these issues but this requires an integral approach using the results of various studies.

Overall aim:

To validate [18]FDG-PET as a biomarker of response in first-line BLBCL therapy using meta-analysis of individual patient data, and to determine its cost-effectiveness.

Objectives

  • To build a PETRA database consisting of individual patient data (including PET scans) of the major international clinical studies on the value of i-PET in lymphomas

  • To determine the optimal timing of i-PET during first-line therapy with R-CHOP of DLBCL

  • To determine which i-PET response criteria perform best in predicting end-of-therapy response rate and progression-free survival at 2 years follow-up in patients with DLBCL

  • To assess whether and how chemo-immunotherapy affects the performance of i-PET

  • To assess whether and how type of NHL affects the performance of interim [18]FDG-PET

  • To determine the cost-effectiveness of i-PET in DLBCL

Publications

Zijlstra, J. M., Burggraaff, C. N., Kersten, M. J., Barrington, S. F., & EHA Scientific Working Group on Lymphoma (2016). FDG-PET as a biomarker for early response in diffuse large B-cell lymphoma as well as in Hodgkin lymphoma? Ready for implementation in clinical practice?. Haematologica, 101(11), 1279–1283. https://doi.org/10.3324/haematol.2016.142752

Burggraaff, C. N., de Jong, A., Hoekstra, O. S., Hoetjes, N. J., Nievelstein, R., Jansma, E. P., Heymans, M. W., de Vet, H., & Zijlstra, J. M. (2019). Predictive value of interim positron emission tomography in diffuse large B-cell lymphoma: a systematic review and meta-analysis. European journal of nuclear medicine and molecular imaging, 46(1), 65–79. https://doi.org/10.1007/s00259-018-4103-3

Zwezerijnen, G., Eertink, J. J., Burggraaff, C. N., Wiegers, S. E., Shaban, E., Pieplenbosch, S., Oprea-Lager, D. E., Lugtenburg, P. J., Hoekstra, O. S., de Vet, H., Zijlstra, J. M., & Boellaard, R. (2021). Interobserver Agreement on Automated Metabolic Tumor Volume Measurements of Deauville Score 4 and 5 Lesions at Interim 18F-FDG PET in Diffuse Large B-Cell Lymphoma. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 62(11), 1531–1536. https://doi.org/10.2967/jnumed.120.258673

Burggraaff, C. N., Cornelisse, A. C., Hoekstra, O. S., Lugtenburg, P. J., De Keizer, B., Arens, A., Celik, F., Huijbregts, J. E., De Vet, H., Zijlstra, J. M., & HOVON Imaging Working Group (2018). Interobserver Agreement of Interim and End-of-Treatment 18F-FDG PET/CT in Diffuse Large B-Cell Lymphoma: Impact on Clinical Practice and Trials. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 59(12), 1831–1836. https://doi.org/10.2967/jnumed.118.210807

Eertink, J. J., Burggraaff, C. N., Heymans, M. W., Dührsen, U., Hüttmann, A., Schmitz, C., Müller, S., Lugtenburg, P. J., Barrington, S. F., Mikhaeel, N. G., Carr, R., Czibor, S., Györke, T., Ceriani, L., Zucca, E., Hutchings, M., Kostakoglu, L., Loft, A., Fanti, S., Wiegers, S. E., … de Vet, H. (2021). Optimal timing and criteria of interim PET in DLBCL: a comparative study of 1692 patients. Blood advances, 5(9), 2375–2384. https://doi.org/10.1182/bloodadvances.2021004467

Barrington, S. F., Eertink, J. J., de Vet, H., George Mikhaeel, N., Hoekstra, O. S., & Zijlstra, J. M. (2021). Not Yet Time to Abandon the Deauville Criteria in Diffuse Large B-Cell Lymphoma. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 62(11), 1655–1656. https://doi.org/10.2967/jnumed.121.262317

Burggraaff, C. N., Eertink, J. J., Lugtenburg, P. J., Hoekstra, O. S., Arens, A., de Keizer, B., Heymans, M. W., van der Holt, B., Wiegers, S. E., Pieplenbosch, S., Boellaard, R., de Vet, H., & Zijlstra, J. M. (2021). 18F-FDG PET improves baseline clinical predictors of response in diffuse large B-cell lymphoma: The HOVON-84 study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, jnumed.121.262205. Advance online publication. https://doi.org/10.2967/jnumed.121.262205

Eertink, J. J., Arens, A., Huijbregts, J. E., Celik, F., de Keizer, B., Stroobants, S., de Jong, D., Wiegers, S. E., Zwezerijnen, G., Burggraaff, C. N., Boellaard, R., de Vet, H., Hoekstra, O. S., Lugtenburg, P. J., Chamuleau, M., Zijlstra, J. M., & HOVON imaging workgroup (2021). Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements. European journal of nuclear medicine and molecular imaging, 10.1007/s00259-021-05498-7. Advance online publication. https://doi.org/10.1007/s00259-021-05498-7