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Intratumoral T cells have a differential impact on FDG-PET parameters in follicular lymphoma.

ABSTRACT: Data on the prognostic impact of pretherapy 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in follicular lymphoma (FL) is conflicting. The predictive utility of pretherapy total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) on outcome appears to vary between regimens. Chemoimmunotherapies vary in the extent of T-cell depletion they induce. The role of intratumoral T cells on pretherapy FDG-PET parameters is undefined. We assessed pretherapy FDG-PET parameters and quantified intratumoral T cells by multiple methodologies. Low intratumoral T cells associated with approximately sixfold higher TMTV, and FL nodes from patients with high TMTV showed increased malignant B-cell infiltration and fewer clonally expanded intratumoral CD8+ and CD4+ T-follicular helper cells than those with low TMTV. However, fluorescently labeled glucose uptake was higher in CD4+ and CD8+ T cells than intratumoral B cells. In patients with FDG-PET performed prior to excisional biopsy, SUVmax within the subsequently excised node associated with T cells but not B cells. In summary, TMTV best reflects the malignant B-cell burden in FL, whereas intratumoral T cells influence SUVmax. This may contribute to the contradictory results between the prognostic role of different FDG-PET parameters, particularly between short- and long-term T-cell-depleting chemoimmunotherapeutic regimens. The impact of glucose uptake in intratumoral T cells should be considered when interpreting pretherapy FDG-PET in FL.

SUBMITTER: Nath K

PROVIDER: S-EPMC8270658 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Intratumoral T cells have a differential impact on FDG-PET parameters in follicular lymphoma.

Nath Karthik K Law Soi-Cheng SC Sabdia Muhammed B MB Gunawardana Jay J de Long Lilia M LM Sester David D Shanavas Mohamed M Tsang Hennes H Tobin Joshua W D JWD Halliday Sarah-Jane SJ Hernandez Annette A Cross Donna D Bird Robert J RJ Jain Sanjiv S Keane Colm C Talaulikar Dipti D Trotman Judith J Law Phillip P Gandhi Maher K MK

Blood advances 20210601 12

Data on the prognostic impact of pretherapy 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in follicular lymphoma (FL) is conflicting. The predictive utility of pretherapy total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) on outcome appears to vary between regimens. Chemoimmunotherapies vary in the extent of T-cell depletion they induce. The role of intratumoral T cells on pretherapy FDG-PET parameters is undefined. We assessed pretherapy FDG-PET p ...[more]

PMID: 34156439

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Project description:At present, 18F-fluorodesoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) cannot be used to omit a bone marrow biopsy (BMB) among initial staging procedures in follicular lymphoma (FL). The additional diagnostic value of skeletal textural features on baseline 18FDG-PET/CT in diffuse large B-cell lymphoma (DLBCL) patients has given promising results. The aim of this study is to evaluate the value of 18FDG-PET/CT radiomics for the diagnosis of bone marrow involvement (BMI) in FL patients. This retrospective bicentric study enrolled newly diagnosed FL patients addressed for baseline 18FDG PET/CT. For visual assessment, examinations were considered positive in cases of obvious bone focal uptakes. For textural analysis, the skeleton volumes of interest (VOIs) were automatically extracted from segmented CT images and analysed using LifeX software. BMB and visual assessment were taken as the gold standard: BMB -/PET - patients were considered as bone-NEGATIVE patients, whereas BMB +/PET -, BMB -/PET + and BMB +/PET + patients were considered bone-POSITIVE patients. A LASSO regression algorithm was used to select features of interest and to build a prediction model. Sixty-six consecutive patients were included: 36 bone-NEGATIVE (54.5%) and 30 bone-POSITIVE (45.5%). The LASSO regression found variance_GLCM, correlation_GLCM, joint entropy_GLCM and busyness_NGLDM to have nonzero regression coefficients. Based on ROC analysis, a cut-off equal to - 0.190 was found to be optimal for the diagnosis of BMI using PET pred.score. The corresponding sensitivity, specificity, PPV and NPV values were equal to 70.0%, 83.3%, 77.8% and 76.9%, respectively. When comparing the ROC AUCs with using BMB alone, visual PET assessment or PET pred.score, a significant difference was found between BMB versus visual PET assessments (p = 0.010) but not between BMB and PET pred.score assessments (p = 0.097). Skeleton texture analysis is worth exploring to improve the performance of 18FDG-PET/CT for the diagnosis of BMI at baseline in FL patients.

Project description:PurposeWe investigated the utility of a new baseline PET parameter expressing lesion dissemination and metabolic parameters for predicting progression-free survival (PFS) and pathologic grade in follicular lymphoma (FL).MethodsThe baseline 18F-FDG PET/CT images of 126 patients with grade 1-3A FL were retrospectively analyzed. A novel PET/CT parameter characterizing lesion dissemination, the distance between two lesions that were furthest apart (D max), was calculated. The total metabolic tumor volume and total lesion glycolysis (TLG) were computed by using 41% of the maximum standardized uptake value (SUVmax) thresholding method.ResultsThe 5-year PFS rate was 51.9% for all patients. In the multivariate analysis, high D max [P = 0.046; hazard ratio (HR) = 2.877], high TLG (P = 0.004; HR = 3.612), and elevated serum lactate dehydrogenase (P = 0.041; HR = 2.287) were independent predictors of PFS. A scoring system for prognostic stratification was established based on these three adverse factors, and the patients were classified into three risk categories: low risk (zero to one factor, n = 75), intermediate risk (two adverse factors, n = 29), and high risk (three adverse factors, n = 22). Patients in the high-risk group had a shorter 3-year PFS (21.7%) than those in the low- and intermediate-risk groups (90.6 and 44.6%, respectively) (P < 0.001). The C-index of our scoring system for PFS (0.785) was superior to the predictive capability of the Follicular Lymphoma International Prognostic Index (FLIPI), FLIPI2, and PRIMA-Prognostic Index (C-index: 0.628-0.701). The receiver operating characteristic curves and decision curve analysis demonstrated that the scoring system had better differentiation and clinical utility than these existing indices. In addition, the median SUVmax was significantly higher in grade 3A (36 cases) than in grades 1 and 2 FL (90 cases) (median: 13.63 vs. 11.45, P = 0.013), but a substantial overlap existed (range: 2.25-39.62 vs. 3.17-39.80).ConclusionTLG and D max represent two complementary aspects of the disease, capturing the tumor burden and lesion dissemination. TLG and D max are promising metrics for identifying patients at a high risk of progression or relapse. Additionally, SUVmax seems to have some value for distinguishing grade 3A from low-grade FL but cannot substitute for biopsy.

Dataset Information

Intratumoral T cells have a differential impact on FDG-PET parameters in follicular lymphoma.

Publications

Intratumoral T cells have a differential impact on FDG-PET parameters in follicular lymphoma.

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