Purpose: The prognostic impact of total metabolic tumor volume (TMTV) measured on pretreatment 18 F-FDG PET/CT and its added value to molecular characteristics was investigated in patients with diffuse large B-cell lymphoma (DLBCL).Experimental Design: For 81 newly diagnosed patients with DLBCL treated with rituximab and CHOP/CHOP-like regimen, TMTV was computed using the 41% SUV max thresholding method. According to the gene expression profile, determined using DASL (cDNA-mediated Annealing, Selection, Ligation and extension) technology, a subset of 57 patients was classified in germinal center B (GCB) or activated B-cell (ABC) subtypes and MYC or BCL2 overexpressed.Results: Median follow-up was 64 months. Five-year progression-free survival (PFS) and overall survival (OS) were 60% and 63% in the whole population. Median pretherapy TMTV was 320 cm 3 (25th-75th percentiles 106-668 cm 3 ). With a 300 cm 3 cutoff, patients with high TMTV (n ¼ 43) had a 5-year PFS and OS of 43% and 46% compared with 76% and 78% for patients with a low TMTV (P ¼ 0.0023, P ¼ 0.0047). ABC status, MYC, or BCL2 overexpression and both overexpression ("dual expressor," DE) were significantly associated with a worse PFS and OS. TMTV combined with molecular data allowed a significant better risk substratification of ABC/GCB patients, on PFS and OS. High TMTV individualized in molecular-low-risk patients a group with a poor outcome (MYC, PFS¼51%, OS¼55% BCL2, PFS¼49%, OS¼49% or DE PFS¼50%, OS¼50%) and a group with a good outcome (MYC, PFS¼93%, OS¼93% BCL2, PFS¼86%, OS¼86%, or DE PFS¼81%, OS¼81%). Conclusions:The combination of molecular and imaging characteristics at diagnosis could lead to a more accurate selection of patients, to increase tailor therapy.

A CS including sarcopenia and adipopenia, assessed by a single CT scan slice, predicts outcome independent of BMI and the IPI.

From a liquid biopsy, cell-free DNA (cfDNA) can provide information regarding basal tumoral genetic patterns and changes upon treatment. In a prospective cohort of 30 diffuse large B-cell lymphomas (DLBCL), we determined the clinical relevance of cfDNA using targeted next-generation sequencing and its correlation with PET scan imaging at the time of diagnosis and during treatment. Using a dedicated DLBCL panel, mutations were identified at baseline for 19 cfDNAs and profiles were consistent with expected DLBCL patterns. Tumor burden-related clinical and PET scan features (LDH, IPI, and metabolic tumor volume) were significantly correlated with the quantity of tumoral cfDNA. Among the four patients presenting additional mutations in their cfDNAs, three had high metabolic tumor volumes, suggesting that cfDNA more accurately reflects tumor heterogeneity than tissues biopsy itself. Mid-treatment, four patients still had basal mutations in their cfDNAs, including three in partial response according to their Deauville scores. Our study highlights the major interests in liquid biopsy, in particular in the context of bulky tumors where cfDNA allows capturing the entire tumoral mutation profile. Therefore, cfDNA analysis in DLBCL represents a complementary approach to PET scan imaging.