Circulating tumor DNA in diffuse large B-cell lymphoma: analysis of response assessment, correlation with PET/CT and clone evolution.

INTRODUCTION: Circulating tumor DNA (ctDNA) can be obtained from cell-free DNA (cfDNA) andis a new technique for genotyping, response assessment and prognosis in lymphoma. METHODS: Eighteen patients with samples at diagnosis (ctDNA1), after treatment (ctDNA2) and extracted from diagnostic tissue (FFPE) were evaluated. RESULTS: In all patients, at least one mutation in cfDNA was detected at diagnosis. CREBBP was the most frequent mutated gene (67 %). In 12 of the 15 patients with complete remission, the mutation attributed to the disease found at diagnosis cleared with treatment. A reduction in the ctDNA was observed after treatment in 14 patients, 12 of whom achieved complete remission. Correlations were found between the ctDNA at diagnosis and total metabolic tumor volume (r = 0.51; p-value = 0.014) and total lesion glycolysis 2.5 (r = 0.47; p-value = 0.024) by PET at diagnosis and between ctDNA at diagnosis and radiomic features of the lesions with the largest standardized uptake value. There was a strong inverse correlation between ΔctDNA1 and ΔSUVmax by PET/CT (r = -0.8788; p-value = 0.002). CONCLUSION: Analysis of ctDNA and PET/CT in large B-cell lymphoma are complementary data for evaluating tumor burden and tumor clearance after treatment. Analysis of radiomic data might help to identify tumor characteristics and their changes after treatment.

Metabolic Volume Measurements in Multiple Myeloma.

Multiple myeloma (MM) accounts for 10-15% of all hematologic malignancies, as well as 20% of deaths related to hematologic malignant tumors, predominantly affecting bone and bone marrow. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (FDG-PET/CT) is an important method to assess the tumor burden of these patients. It is often challenging to classify the extent of disease involvement in the PET scans for many of these patients because both focal and diffuse bone lesions may coexist, with varying degrees of FDG uptake. Different metrics involving volumetric parameters and texture features have been proposed to objectively assess these images. Here, we review some metabolic parameters that can be extracted from FDG-PET/CT images of MM patients, including technical aspects and predicting MM outcome impact. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters known to be independent predictors of MM outcome. However, they have not been adopted in clinical practice due to the lack of measuring standards. CT-based segmentation allows automated, and therefore reproducible, calculation of bone metabolic metrics in patients with MM, such as maximum, mean and standard deviation of the standardized uptake values (SUV) for the entire skeleton. Intensity of bone involvement (IBI) is a new parameter that also takes advantage of this approach with promising results. Other indirect parameters obtained from FDG-PET/CT images, such as visceral adipose tissue glucose uptake and subcutaneous adipose tissue radiodensity, may also be useful to evaluate the prognosis of MM patients. Furthermore, the use and quantification of new radiotracers can address different metabolic aspects of MM and may have important prognostic implications.

Intensity of bone involvement: a quantitative 18F-FDG PET/CT evaluation for monitoring outcome of multiple myeloma.

PURPOSE: The parameter intensity of bone involvement (IBI) was recently proposed to quantitatively assess patients with multiple myeloma using 18F-fluorodeoxyglucose-PET combined with computed tomography (18F-FDG PET/CT) images. Here, we aimed to calculate IBI variation (ΔIBI) between two consecutive PET/CT of the same patient and verified its relationship with a subjective visual analysis of the images and with clinical outcome. METHODS: Consecutive whole-body 18F-FDG PET/CT performed to assess the outcomes of 29 patients diagnosed with multiple myeloma were retrospectively evaluated. ΔIBI was calculated after bone segmentation, using liver standardized uptake value as a threshold to determine metabolically active volumes in the skeleton. For each pair of consecutive PET/CTs, two nuclear medicine physicians classified visually the most recent image as PET-remission, PET-progression or PET-stable when compared to the previous examination. RESULTS: The lowest ΔIBI was -1.27 and the highest was 0.29. PET-remission was related to ΔIBI <0 (median = -0.10; -1.27 to +0.03), while PET-progression was related to ΔIBI >0 (median = 0.02; -0.07 to +0.29). ΔIBI around zero was found in images classified as PET-stable (median = 0.00; -0.08 to +0.06). Significant difference in ΔIBI was found between the three groups. Multivariate stepwise analysis showed that IBI value at diagnostic PET/CT, serum calcium and percentage of plasma cells in the bone marrow are independent prognostic factors. CONCLUSION: Delta IBI provides quantitative data for variations of 18F-FDG uptake in the bone marrow during the follow-up of the patients. In addition, higher IBI values at diagnosis are associated with a higher risk of patient's death.

Visceral adipose tissue glucose uptake is linked to prognosis in multiple myeloma patients: An exploratory study.

BACKGROUND & AIMS: The use of computerized tomography to opportunistically assess body composition has highlighted abnormalities such as low muscle mass and high adiposity may be hidden conditions in cancer patients. However, the role of skeletal muscle (SM), subcutaneous (SAT) and visceral (VAT) adipose tissue glucose uptake measured by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-CT on patient prognostication is unclear. METHODS: Patients with multiple myeloma (MM) with satisfactory image frame for assessing body composition and for semi-quantification of SM, SAT and VAT glucose uptakes were included. Plasmatic pro-inflammatory cytokine and adipokine levels were measured. RESULTS: High VAT mean standardized uptake value (SUV) at baseline was associated with shorter event-free survival (EFS) (hazard ratio [HR]: 7.89; 95% confidence interval [CI], 1.58-39.30; P = 0.012) and overall survival (OS) (HR, 15.24; 95% CI, 2.69-86.30; P = 0.002) among patients with newly diagnosed MM, even after adjustment for covariates. The highest tertile of VAT SUV was significantly correlated with worse MM-EFS (HR for the highest vs the lowest tertile 3.71; 95% CI, 1.22-10.56; Ptrend = 0.035) and mortality (HR, 4.41; 95% CI, 1.28-12.77; Ptrend = 0.019). Notably, patients with higher VAT SUV presented with lower VAT area, VAT index, higher SAT SUV, and higher number of individuals with visceral obesity (all P < 0.01). Additionally, we found a negative correlation between VAT mean SUV with leptin (R2 = 0.20, P = 0.003); no correlations were detected between VAT mean SUV and resistin, tumor necrosis factor (TNF) or interleukin (IL)-6. CONCLUSIONS: Functional VAT activity estimated by 18F-FDG PET-CT is a relevant prognostic factor in MM patients, specifically, a higher VAT SUV might be an early biomarker of cancer cachexia in these patients.

Adipose tissue radiodensity: A new prognostic biomarker in people with multiple myeloma.

OBJECTIVES: Standard prognostic markers based on individual characteristics of individuals with multiple myeloma (MM) remain scarce. Body-composition features have often been associated with survival outcomes in different cancers. However, the association of adipose tissue radiodensity with MM prognosis has not yet, to our knowledge, been explored. METHODS: Computed tomography at the third lumbar vertebra was used for body-composition analysis, including adipose tissue radiodensity, in 91 people with MM. Additionally, fludeoxyglucose F 18 (18F-FDG) positron emission tomography was used to assess adipose tissue 18F-FDG uptake. Proinflammatory cytokine and adipokine levels were measured. RESULTS: Event-free survival and overall survival were both shorter in participants with high subcutaneous adipose tissue (SAT) radiodensity. Those in the highest SAT radiodensity tertile had an independently higher risk for both overall survival (hazard ratio, 4.55; 95% confidence interval, 1.26-16.44; Ptrend = 0.036) and event-free survival (hazard ratio, 3.08; 95% confidence interval, 1.02-9.27; Ptrend = 0.035). Importantly, higher SAT radiodensity was significantly correlated with increased 18F-FDG adipose tissue uptake and proinflammatory cytokine (tumor necrosis factor and interleukin-6) levels, and with decreased leptin levels. CONCLUSIONS: SAT radiodensity may serve as a biomarker to predict host-related metabolic and proinflammatory milieu, which ultimately correlates with MM prognosis.