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Prognostic value of [18F]FDG PET/CT in patients with CNS lymphoma receiving ibrutinib-based therapies

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Current clinical and imaging tools remain suboptimal for predicting treatment response and prognosis in CNS lymphomas. We investigated the prognostic value of baseline [18F]FDG PET in patients with CNS lymphoma receiving ibrutinib-based treatments.

Methods

Fifty-three patients enrolled in a prospective clinical trial and underwent brain PET before receiving single-agent ibrutinib or ibrutinib in combination with methotrexate with or without rituximab. [18F]FDG uptake in these lesions was quantified by drawing PET volumes of interest around up to five [18F]FDG-avid lesions per patient (with uptake greater than surrounding brain). We measured standardized uptake values (SUVmax), metabolic tumor volumes, total lesion glycolysis (TLG), and the sum thereof in these lesions. We analyzed the relationship between PET parameters and mutation status, overall response rates, and progression-free survival (PFS).

Results

Thirty-eight patients underwent single-agent therapy and 15 received combination therapy. On PET, 15/53 patients had no measurable disease. In the other 38 patients, a total of 71 lesions were identified on PET. High-intensity [18F]FDG uptake and a larger volume of [18F]FDG-avid disease were inversely related to treatment outcome (p ≤ 0.005). In univariable analysis, PFS was linearly correlated with all PET parameters, with stronger association when sum-values were used. A multivariable model showed that risk of progression increased by 9% for every 5-unit increase in sumSUVmax (hazard ratio = 1.09 [95% CI: 1.04 to 1.14]).

Conclusion

Higher lesional metabolic parameters are inversely related to outcome in patients undergoing ibrutinib-based therapies, and sumSUVmax emerged as a strong independent prognostic factor.

Trial registration

NCT02315326; https://clinicaltrials.gov/ct2/show/NCT02315326?term=NCT02315326&draw=2&rank=1

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Acknowledgements

We thank Leah Bassity for her expert editorial support.

Funding

This work was supported by a research grant from Pharmacyclics to MSK. Pharmacyclics was not involved in the design or conduct of the study. The statistical analysis plan and data analyses were performed by MSK investigators. This study was partially supported by the National Institutes of Health/National Cancer Institute Cancer Center Support Grant (P30 CA008748), National Institutes of Health/National Cancer Institute Paul Calabresi Career Development Award for Clinical Oncology (K12 CA184746 to S.K.), and National Institutes of Health MSK SPORE in Lymphoma (P50 CA192937 to S.K.), as well as by grants from Cycle for Survival Equinox (C.G.) and the Leukemia & Lymphoma Society (C.G.).

Author information

Author notes

  1. Heiko Schöder and Christian Grommes contributed equally as senior authors

Authors and Affiliations

  1. Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 77, New York, NY, 10065, USA

    Simone Krebs & Heiko Schöder

  2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Audrey Mauguen

  3. Neuroradiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Onur Yildirim & Vaios Hatzoglou

  4. Ophthalmic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jasmine H. Francis

  5. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Lauren R. Schaff, Ingo K. Mellinghoff & Christian Grommes

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  1. Simone Krebs
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Contributions

Conceived and designed the study: S.K., C.G., and H.S.; collected, analyzed, and interpreted the data: S.K., A.M., O.Y., V.H., J.H.F., L.R.S., I.K.M., C.G., and H.S.; performed statistical analysis: A.M.; wrote the manuscript: S.K., C.G., and H.S.; reviewed the data and edited and approved the final version of the manuscript: all authors.

Corresponding author

Correspondence to Heiko Schöder.

Ethics declarations

Ethical approval

All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed written consent was obtained from all individual participants included in the study.

Competing interests

C.G. reports consulting for BTG International and Kite. The remaining authors have no competing interests.

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This article is part of the Topical Collection on Oncology – Brain

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Krebs, S., Mauguen, A., Yildirim, O. et al. Prognostic value of [18F]FDG PET/CT in patients with CNS lymphoma receiving ibrutinib-based therapies. Eur J Nucl Med Mol Imaging 48, 3940–3950 (2021). https://doi.org/10.1007/s00259-021-05386-0

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