Stefan V. Dubois

Bone marrow 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography cannot replace bone marrow biopsy in diffuse large B-cell lymphoma

This study aimed to investigate whether visual and quantitative 18F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography/computed tomography (FDG‐PET/CT)‐based bone marrow assessment can replace blind bone marrow biopsy (BMB) in newly diagnosed diffuse large B‐cell lymphoma (DLBCL). This retrospective study included 78 patients with newly diagnosed DLBCL who had undergone both FDG‐PET/CT and BMB. FDG‐PET/CT images were visually evaluated for bone marrow involvement. Patient‐based sensitivity of visual FDG‐PET/CT assessment was calculated using BMB as the reference standard. Metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, and 3D partial volume corrected mean metabolic volume product (cMVPmean) of FDG‐avid bone marrow lesions were measured. Cox regression analysis was used to determine the influence of (potential) prognostic factors (BMB status, visual [dichotomous] FDG‐PET/CT bone marrow status, metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, 3D partial volume corrected mean metabolic volume product, and International Prognostic Index score) on progression‐free survival and overall survival. FDG‐PET/CT detected bone marrow involvement in 34 (43.6%) cases and BMB in 16 (20.5%) of 78 cases, of whom 11 were also detected by FDG‐PET/CT, resulting in a patient‐based sensitivity of 68.8% (95% confidence interval = 44.2%–86.1%) for FDG‐PET/CT. In the multivariate Cox proportional hazards model, only BMB status was an independent predictive factor of progression‐free survival (P = 0.016) and overall survival (P = 0.004). In conclusion, FDG‐PET/CT misses bone marrow involvement that has been detected by BMB in a non‐negligible proportion of patients. Furthermore, both visual and quantitative FDG‐PET/CT‐based bone marrow assessments are prognostically inferior to BMB. Therefore, FDG‐PET/CT cannot replace BMB in newly diagnosed DLBCL. Am. J. Hematol. 89:726–731, 2014.

Prognostic superiority of the National Comprehensive Cancer Network International Prognostic Index over pretreatment whole-body volumetric-metabolic FDG-PET/CT metrics in diffuse large B-cell lymphoma

This study aimed to determine the prognostic value of whole‐body maximum standardized uptake value (SUVmax), whole‐body metabolic tumor volume (MTV), and whole‐body total lesion glycolysis (TLG) at pretreatment 18F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography/computed tomography (FDG‐PET/CT) in patients with newly diagnosed diffuse large B‐cell lymphoma (DLBCL).

Diffusely increased bone marrow FDG uptake in recently untreated lymphoma: incidence and relevance.

To determine the incidence of diffusely increased bone marrow 18F‐fluoro‐2‐deoxy‐D‐glucose (FDG) uptake at positron emission tomography (PET) in recently untreated lymphoma and to assess the frequency of lymphoma‐positive bone marrow biopsies (BMBs) in these patients.

Direct comparison of visual and quantitative bone marrow FDG-PET/CT findings with bone marrow biopsy results in diffuse large B-cell lymphoma: does bone marrow FDG-PET/CT live up to its promise?

Background Detection of bone marrow involvement using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been proposed as a non-invasive alternative to standard blind bone marrow biopsy (BMB) of the posterior iliac crest in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, studies that directly compare FDG-PET/CT results with histopathology are currently lacking. Purpose To directly compare both visual and quantitative bone marrow FDG-PET/CT to BMB at the right posterior iliac crest in patients with newly diagnosed DLBCL. Material and Methods A total of 40 patients with newly diagnosed DLBCL, who had undergone FDG-PET/CT before BMB of the right posterior iliac crest, were retrospectively included. FDG-PET/CT images were visually assessed for bone marrow involvement in the right posterior iliac crest. 3D partial volume corrected mean standardized uptake value (cSUVmean), maximum standardized uptake value (SUVmax), and peak standardized uptake value (SUVpeak) were measured in the right posterior iliac crest, using volume of interest analysis. BMB of the right posterior iliac crest was used as reference standard for bone marrow involvement. Results Sensitivity and specificity of visual FDG-PET/CT analysis for the detection of bone marrow involvement in the right posterior iliac crest were 14.3% (95% confidence interval [CI], 0.5–53.4%) and 100% (95% CI, 87.6–100%), respectively. cSUVmean, SUVmax, and SUVpeak of BMB-negative patients (1.4 ± 0.49, 2.2 ± 0.69, and 1.7 ± 0.59, respectively) considerably overlapped with those of BMB-positive patients (1.8 ± 0.53, 2.7 ± 0.71, and 2.2 ± 0.61, respectively). Conclusion In a local, head-to-head comparison with BMB, the diagnostic value of both visual and quantitative FDG-PET/CT for the detection of bone marrow involvement is low in patients with newly diagnosed DLBCL.

Bone marrow biopsy in diffuse large B-cell lymphoma: Useful or redundant test?

Abstract Purpose. To determine the additional value of bone marrow biopsy (BMB) in the standard staging work-up of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), in terms of risk assessment and treatment planning. Material and methods. A total of 113 consecutive patients with newly diagnosed DLBCL who had undergone standard pretreatment evaluation, including serum lactate dehydrogenase measurement, Eastern Cooperative Oncology Group performance status assessment, computed tomography or 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography, and BMB, were retrospectively included. National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score and treatment strategy were determined in each patient, once without and once with taking into account BMB results. Numbers and percentages of BMB-induced changes on NCCN-IPI-based risk stratification (i.e. formation of low, low-intermediate, high-intermediate, and high risk groups) and choice of treatment were calculated, along with 95% confidence intervals (CIs). Results. BMB was positive in 18 of 113 patients (15.9%, 95% CI 10.2–23.9 %). BMB-induced changes on NCCI-IPI-based risk stratification occurred in 9 of 113 patients (8.0%, 95% CI 4.1–14.6%). Five patients were upstaged from low-intermediate to high-intermediate risk, and four patients were upstaged from high-intermediate to high risk. BMB findings changed treatment planning in none of the 113 patients (0.0%, 95% CI 0.0–4.0%). Conclusion. Although BMB results upstaged the NCCN-IPI-based risk stratification in a small number of cases, this did not have any therapeutic implications in our patient series. These findings support the omission of BMB from routine staging of newly diagnosed DLBCL in the current risk stratification and treatment era.

Variety in bone marrow 18F-FDG uptake in Hodgkin lymphoma patients without lymphomatous bone marrow involvement: does it have an explanation?

ObjectiveTo directly correlate fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG) uptake of the iliac crest, as determined with PET, with both spatially matched histological bone marrow parameters and laboratory markers in Hodgkin lymphoma patients without lymphomatous bone marrow involvement at bone marrow biopsy. Materials and methodsThis retrospective study included 21 patients with newly diagnosed Hodgkin lymphoma who underwent 18F-FDG-PET and who had a lymphoma-negative bone marrow biopsy of the right posterior iliac crest. 18F-FDG-PET maximum standardized uptake value (SUVmax) was measured in the right posterior iliac crest and correlated to histological bone marrow parameters (cellularity, myeloid/erythroid ratio, degree of fibrosis, and reactive T- and B-lymphocytes) and laboratory markers (hemoglobin, C-reactive protein lactate dehydrogenase, and leukocyte and thrombocyte counts) using Pearson’s correlation coefficient (R) for Gaussian data or Kendall’s tau (&tgr;) for non-Gaussian data. ResultsThere was a significant moderate correlation between 18F-FDG-PET SUVmax and cellularity of the iliac crest (R=0.519, P=0.016). Furthermore, there was a significant strong inverse correlation between 18F-FDG-PET SUVmax of the iliac crest and hemoglobin level (R=−0.661, P=0.001) and there was a significant moderate correlation between 18F-FDG-PET SUVmax of the iliac crest and C-reactive protein level (&tgr;=0.441, P=0.007). All other correlations, including 18F-FDG-PET SUVmax of the right iliac crest versus reactive T- and B-lymphocytes in the bone marrow, were not significant. ConclusionThe observations suggest increased bone marrow 18F-FDG uptake to be caused by red marrow hyperplasia because of anemia in Hodgkin lymphoma. Increased bone marrow 18F-FDG uptake is unlikely to be caused by inflammatory bone marrow changes.

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma.

OBJECTIVE To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. RESULTS There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ=-0.042, P=0.765), categorized lactate dehydrogenase (LDH) ratio (ρ=0.201, P=0.156), extranodal disease in major organs (φ=-0.245, P=0.083), Ann Arbor stage III/IV disease (φ=-0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ=0.015, P=0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P=0.004). CONCLUSION The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

Tumor necrosis at FDG-PET is an independent predictor of outcome in diffuse large B-cell lymphoma

PURPOSE To determine the prognostic performance of tumor necrosis at FDG-PET in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who are treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. MATERIALS AND METHODS 108 patients with newly diagnosed DLBCL who underwent FDG-PET before R-CHOP therapy were retrospectively included. Lymphomatous sites at FDG-PET were assessed for the presence of a photopenic area, in keeping with tumor necrosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of tumor necrosis and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) with progression-free survival (PFS) and overall survival (OS). RESULTS On univariate Cox regression analysis, both tumor necrosis and higher NCCN-IPI risk groups were significantly associated with PFS (P=0.024 and P<0.001, respectively) and OS (P=0.034 and P<0.001, respectively). On multivariate Cox regression analysis, both tumor necrosis and the NCCN-IPI were independent significant predictors for PFS (P=0.007, hazard ratio: 2.723 [95% confidence interval: 1.324-5.597] and P<0.001, hazard ratio: 2.952 [95% confidence interval: 1.876-4.646], respectively) and OS (P=0.009, hazard ratio: 2.794 [95% confidence interval: 1.305-5.985] and P<0.001, hazard ratio: 2.813 [95% confidence interval: 1.724-4.587], respectively). CONCLUSION Tumor necrosis at FDG-PET is an NCCN-IPI-independent predictor of outcome in DLBCL.

Residual anatomical disease in diffuse large B-cell lymphoma patients with FDG-PET-based complete response after first-line R-CHOP therapy : Does it have any prognostic value?

Objective This study aimed to determine the prognostic value of residual anatomical disease, including its size and reduction relative to baseline, in diffuse large B-cell lymphoma patients who have 18F-fluoro-2-deoxy-d-glucose positron emission tomography–based complete response after first-line R-CHOP therapy. Methods This retrospective study included 47 patients. In patients with computed tomography (CT)–based residual disease, the size of the largest residual lesion (Resmax) and the sum of the sizes of all residual lesions (Restotal) were measured, and their reductions relative to baseline (&Dgr;Resmax and &Dgr;Restotal) were calculated. Results Patients with high-risk National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) scores had significantly lower progression-free survival (PFS) and overall survival (OS) than patients with low-risk NCCN-IPI scores (P = 0.032 and P = 0.022). In contrast, patients with residual lesions at CT had no significantly lower PFS and OS than those without (P = 0.531 and P = 0.801). In the subpopulation with CT-based residual disease, patients with high Resmax, high Restotal, low &Dgr;Resmax, and low &Dgr;Restotal had no significantly different PFS and OS than those with low Resmax, low Restotal, high &Dgr;Resmax, and high &Dgr;Restotal (P = 0.980 and P = 0.790, P = 0.423 and P = 0.229, P = 0.923 and P = 0.893, and P = 0.923 and P = 0.893, respectively). Conclusions The NCCN-IPI retains its prognostic value in diffuse large B-cell lymphoma patients with 18F-fluoro-2-deoxy-d-glucose positron emission tomography–based complete response after first-line R-CHOP therapy. However, the presence of residual anatomical disease, including its size and reduction relative to baseline, has no prognostic value in these patients.

Paget's disease of the bone mimicking lymphomatous bone marrow involvement at FDG-PET

Image 1. Coronal (A), oblique (B), and sagittal (C) 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (FDG-PET) maximum intensity projections (MIPs) showing multiple FDG-avid lesions throughout the skeleton. FDG-PET (D), CT (E), and biopsy results (F, G, H) of retroperitoneal mass showing a CD20 positive proliferation of atypical B-cells, consistent with follicular lymphoma grade 3A. FDG-PET (I), CT (J), and bone marrow biopsy (K, L, M) of right iliac crest showing Paget’s disease.