Bone marrow infiltration assessment by fdg18-pet: can this imaging test replace bone marrow trephine biopsy in diffuse large b cell lymphoma staging?

Introduction: Bone marrow assessment (BMI) is an important part of disease staging in lymphoma, and includes FDG18-PET and BM trephine biopsy (BMB), which is the gold-standard for detecting BM infiltration. Nevertheless, studies indicate that PET accurately detects BMI in aggressive lymphomas. We aimed to assess the accuracy of PET in detecting BMI in diffuse large B-cell lymphoma (DLBCL). Methods: Single centre retrospective analysis of 335 patients (pts) diagnosed with DLBCL from 2010 to 2019. BMB and PET data at diagnosis was available in 144 pts. Agreement between PET and BMB findings was assessed by Cohen's k computation. For survival analysis, Cox regression model was used. Results: A total of 144 pts underwent PET and BMB, 57% males, median age 63 years (22-89). Positive BMB (BMB+) was observed in 22 (15%) pts (19 with BMI by DLBCL and 3 by discordant low-grade lymphoma). Positive PET (PET+) was observed in 36 (25%) pts (diffuse BMI pattern in 18 pts, focal in 16 and both in 2 pts). At diagnosis, 92% of all PET+ pts presented with advanced stage disease due to extra-medullary organ involvement (AdS). Concordant detection of BMI by PET and BMB was observed in 14 pts. Twenty-two pts with PET+ (out of 36) were missed by BMB (BMB-), 12 of these with focal BMI pattern. BMI was not detected by PET in 8/22 BMB+ pts (2/8 with low-grade lymphoma in BMB). Only 8/108 (7%) pts with PET- had BMB+ and 22/122 (18%) pts with BMB- showed PET+. We observed a moderate agreement between PET and BMB (k = 0.36; p < 0.001). Considering BMB as the gold standard for BMI, the sensitivity and specificity of PET for BMI assessment were 64% (95%CI: 41-82%) and 82% (95%CI: 74-88%), respectively. PPV (positive predictive value) was 39% (95%CI: 24-56%) and NPV (negative predictive value) was 93% (95%CI: 85-97%). In our cohort, the progression free survival (PFS) at 5 years (yrs) was 58%. Median PFS for BMB- and BMB+ was NR (not reached) and 25 months, respectively (HR 1.68; p = 0.097). For BMI by PET, PFS was NR and 15.8 months for PET- and PET+, respectively, significantly higher in PET- group (HR 2.49; p = 0.001). The negative impact of PET positivity in PFS became not significant after multivariate analysis for different prognostic variables. Total overall survival (OS) at 5 yrs was 67%. Median OS was NR for both BMB- and BMB+ (HR 1.61; p = 0.181; 70% and 53% at 5 yrs) and NR for both PET- and PET+ (HR 1.70; p = 0.084; 72% and 51% at 5 yrs). Conclusions: We showed a higher specificity of FDG18-PET over BMB in BMI assessment in DLBCL. In fact, a higher number of pts presented BMI by PET compared with BMB, which may have failed to detect focal BMI. However, although we showed that BMI by PET had a negative impact on global PFS, further studies are necessary to clarify if BMI adds a negative impact on survival of DLBCL pts with AdS already in PET staging. Contrastingly, PET sensitivity in detecting BMI was lower which may be related to its low avidity for low tumour burden and low volume disease. Keywords: Diagnostic and Prognostic Biomarkers, PET-CT, Aggressive B-cell non-Hodgkin lymphoma No conflicts of interest pertinent to the abstract.