FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials

Dominic Kaddu-Mulindwa, Bettina Altmann, Gerhard Held, Stephanie Angel, Stephan Stilgenbauer, Lorenz Thurner, Moritz Bewarder, Maren Schwier, Michael Pfreundschuh, Markus Löffler, Karin Menhart, Jirka Grosse, Marita Ziepert, Ken Herrmann, Ulrich Dührsen, Andreas Hüttmann, Francesco Barbato, Viola Poeschel, Dirk Hellwig, Dominic Kaddu-Mulindwa, Bettina Altmann, Gerhard Held, Stephanie Angel, Stephan Stilgenbauer, Lorenz Thurner, Moritz Bewarder, Maren Schwier, Michael Pfreundschuh, Markus Löffler, Karin Menhart, Jirka Grosse, Marita Ziepert, Ken Herrmann, Ulrich Dührsen, Andreas Hüttmann, Francesco Barbato, Viola Poeschel, Dirk Hellwig

Abstract

Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB).

Methods: Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy.

Results: Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32-45%) and 84% (CI: 78-88%), specificity 100% (CI: 99-100%) and 100% (CI: 99-100%), positive predictive value 100% (CI: 96-100%) and 100% (CI: 98-100%), and negative predictive value 84% (CI: 81-86%) and 95% (CI: 93-97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management.

Conclusion: In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted.

Trial registration: NCT00554164 and NCT01478542.

Keywords: Aggressive B-cell lymphoma; Bone marrow biopsy; Diagnostic performance; FDG PET/CT; Lymphoma.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Consort diagram of patients from the PETAL and OPTIMAL>60 trials included in the bone marrow analysis
Fig. 3
Fig. 3
Female patient with diffuse large B-cell lymphoma and multifocal bone marrow involvement at baseline FDG PET/CT (INI), which was missed by bone marrow biopsy and remitted completely after 6 cycles of chemoimmunotherapy (RE2). Maximum-intensity projections in frontal and lateral view
Fig. 2
Fig. 2
Baseline FDG PET (maximumintensity projection in frontal view) of a male patient with diffuse large B-cell lymphoma. FDG uptake in bone marrow space (with an intensity markedly above that in the liver) is diffusely increased without any focus in the bone marrow space apart from the biopsy site (right iliac crest, outlined arrow), but with asymmetric uptake (filled arrow) in right and left proximal humerus (maximum standardized uptake value 7.0 and 3.6, respectively) consistent with bone marrow involvement as confirmed by bone marrow biopsy. CT (not shown) revealed no osseous involvement in the proximal right humerus. Focal uptake in cartilage-bone junctions (outlined arrow-heads) as foci attributable to benign conditions

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