Background: Bone marrow evaluation (BME) is crucial for establishing an accurate staging and prognosis in lymphoma patients. Objective: The objective of the study was to study the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) against bone marrow biopsy (BMB) for BME. Methods: Five hundred patient files of newly diagnosed lymphoma patients treated at an academic medical center were reviewed for BME at diagnosis by BMB and FDG PET-CT. Diagnostic performance of FDG PET-CT for detecting bone marrow infiltration (BMI) was assessed, as well as clinical predictors for positive BMB and positive FDG PET-CT. Results: BMB was positive in 16.3% of all patients, and 28.7% had a positive FDG PET-CT for BMI. Overall, the sensitivity of FDG PET-CT was 74.1% and specificity 80.1%. As for predictors for BMB and FDG PET-CT positivity, B symptoms and thrombocytopenia were independent factors for BMI. Seventy-four patients had discordant results between BMB and FDG PET-CT, non-Hodgkin lymphoma (NHL) having the most significant discordance. This discrepancy did not affect treatment. Conclusions: FDG PET-CT shows excellent performance for the detection of BMI in Hodgkin lymphoma. For diffuse large B-cell lymphoma, we recommend performing BMB and FDG PET-CT as complementary tests. In all other NHL, a unilateral BMB is mandatory at diagnosis. (REV INVEST CLIN.
Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Although PET/CT has allowed a better diagnostic evaluation in these patients, none metabolic index has been incorporated into prognostic scores, neither molecular markers have been associated with PET/CT findings. Aim: To define the association between PET/CT findings and EZH2 mutations, and their impact on survival of patients with DLBCL. Methods: Patients: A cohort study of newly diagnosed DLBCL patients. Cohorts were defined according to the presence of EZH2 (Y641N/Y641F/Y641H/Y641S) mutations. Clinical variables were: age, comorbidities, IPI score, bulky disease, clinical stage, serum albumin, LDH and B2-microglobulin levels, and ECOG. Histopathologic variables were GC (Germinal center) versus no-GC by Hans nomogram, BCL2, BLC6, & MYC expression, as well as double-hit. All patients were treated with six cycles of standard RCHOP. PET/CT assessed parameters were: Total metabolic tumor volume (TMV), Total lesion glycolysis (TLG) and SUV max. Clinical response was evaluated by PET/CT, using Deauville's criteria. All 18F-FDG PET/CT scans were performed using the Biograph 16 PET/CT scanner (Siemens AG, Munich, Germany). Patients fasted for at least 6 h prior to intravenous (IV) administration of 18F-FDG (5.5 MBq/kg body weight) to ensure a serum glucose level of <10 mmol/l. Methods: DNA was extracted from paraffin-embedded tissue. PCR analysis was carried out in a 2700 Thermalcycler (Applied Biosystems) to detect mutations in Exon 16 of EZH2; the sequencing and electrophoresis of PCR products was performed using ABI3100 genetic analyser. Sequences were compared with the EZH2 reference sequence (GenBank NG_032043.1). The protocol was approved by IRB (Approval number CEI/966/15). Statistics: After descriptive analysis, mean metabolic indexes were compared by ANOVA between patients with wt and any of the EZH2 mutations . Kaplan-Meier method was used to construct Disease-free survival (DFS) curves and the Log-rank test was used for comparisons. COR curves were used to evaluate metabolic indexes as risk factors infuencing on DFS. Results: Results: 230 patients (120 male), were included. Median age was 58.3 years (SD 14.25; range: 21-91); 169 of them (73.4%) had advanced disease and 224 (97.3%) had ECOG <2. Absence of B symptoms or bulky disease was documented in 154 (67%) and 136 cases (59.1%), respectively. GC-type was found in 65%. Although sixty cases (26%) were considered to be DLBCL double expressor (MYC +BLC2 overexpression), only 15% were double-hit DLBCL. Mutations at codon 641, exon 16 of EZH2 were described in 15% of cases, as follows: Tyr 641 Asn (Y641N) [6 %],Tyr 641 Phe(Y641F) [6%], Tyr 641 His (Y641H) [3%] and Tyr 641Ser (Y641S) [1%]. Any clinical parameter was different between wt and any EZH2 mutations. However, regarding metabolic indexes by PET/CT, TLG was higher in EZH2 mutated patients (mean: 8314.02g [95 %CI: 5623-11004g]), in comparsion with wt patients (mean: 5228.99g, [ 95 % CI: 4114-6316g], p=0.02). Response was classified as complete in 75% of cases, partial in 3.5%, and progressive disease in 11%. The association of these mutations on DFS is shown in table 1. In addition, mean TLG and TMV indexes were lower in patients without relapse. (Table 2) Summary/Conclusion: These preliminary results suggest that patients with any of EZH2 (Y641F) mutations have a higher TLG by PET/CT at diagnosis, and both values have a negative impact on DFS of patients with DLBCL. Our results need to be confirmed on a larger sample and a longer follow-up. Disclosures No relevant conflicts of interest to declare.
Background: Defining the extent of disease is essential for determining the prognosis and management of patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL) as the presence of advanced disease, including involvement of an extralymphatic site, is associated with inferior outcomes (Cheson et al, 2014). 18F-fluorodeoxyglucose positron emission tomography (FDG PET-CT) has an excellent diagnostic performance for evaluation of bone marrow infiltration (BMI) in patients with lymphoma but it is expensive and not always available at low and middle-income health care facilities. Unilateral bone marrow biopsy (BMB) is a more accessible test and has been the standard to identify lymphomatous BMI. Unfortunately, it is an unpleasant procedure for the patient and can be limited by technical constraints. The aim of this single-center retrospective cohort study was to evaluate the diagnostic performance of FDG PET-CT for BMI in lymphoma patients, comparing it with BMB as the gold standard. Also, we evaluated for discordant results between both studies along with its effect on patient treatment. Methods: Newly diagnosed lymphoma patients evaluated at the National Cancer Institute between July 2017 and December 2018 were identified from our institutional lymphoma data base. Five hundred patient files were reviewed for bone marrow evaluation at diagnosis by BMB and FDG PET-CT as well as for other clinical characteristics. Only 355 patients had both FDG PET-CT and BMB performed and adequately reported, so the rest were excluded from the analysis. Fisher's exact and Pearson Chi-square tests were used to compare categorical variables. Comparisons of continuous variables were performed using Mann-Whitney U test. Setting BMB as the gold standard, diagnostic performance of FDG PET-CT for detecting BMI was evaluated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (LR) and accuracy were calculated for the most common histological subtypes. Logistic regression model was used for univariate and multivariate analysis of predictors for positive BMB and positive FDG PET-CT for BMI. Results: The most common histologic type was diffuse large B-cell lymphoma (DLBCL) in 42.4% of cases, followed by HL in 20.4%, and follicular lymphoma (FL) in 11.2%. Median age was 53 years. B symptoms were present in 59.6% of cases and 71.4% debuted with advanced stage of disease (Ann Arbor III and IV). BMB was positive in 17% of all patients and 28% had a positive FDG PET-CT for BMI (Table 1). BMB was positive in 17.2% of HL, 12.3% of DLBCL, 29.8% of FL and 15.6% of other types of lymphoma patients. Overall, sensitivity of FDG PET-CT was 74.1%, specificity 80.1%, PPV 42.2%, NPV 94.1%, +LR 3.73, -LR 0.32 and accuracy 79.2%. The diagnostic performance of FDG PET-CT in patients with HL, DLBCL, FL and other types of lymphoma is shown in Table 2. As for predictors for BMB positivity, the presence of B symptoms, neutropenia and thrombocytopenia were independent factors for BMI with adjusted OR of 2.44, 95% CI (1.19, 4.99), 5.64, 95% CI (1.32, 24.08) and 4.12, 95% CI (1.66, 10.26), respectively. For positive FDG PET-CT, the presence of B symptoms, thrombocytopenia and advance stage remained significant with adjusted OR of 2.96, CI 95% (1.73, 5.05), 2.75, 95% CI (1.17, 6.48) and 19.22, 95% CI (5.90, 62.66), respectively. Seventy-four patients had discordant results between BMB and FDG PET-CT. The discrepancy in BMB and FDG PET-CT results did not have an effect on treatment. Conclusions: In addition to international clinical practice guidelines recommendations, in our center we recommend performing a BMB to those patients with HL and FDG PET-CT negative for BMI who present with cytopenias and B symptoms at the time of diagnosis. For patients with DLBCL our FDG PET-CT sensitivity was lower than expected, so we recommend a complementary BMB to all DLBCL patients with a positive FDG PET-CT for BMI (stage IV) that otherwise would be early stages (I and II) and would benefit from less aggressive therapy. In all other NHL including FL, we recommend performing a unilateral BMB with immunohistochemical analyses and flow cytometry, if available, for initial evaluation of BMI. Still in the absence of FDG PET-CT, a whole-body contrast-enhanced CT along with a unilateral posterior iliac crest BMB could adequately stage most types of lymphoma at low and middle-income health care facilities. Disclosures No relevant conflicts of interest to declare.
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