Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma

Purpose: The prognostic impact of total metabolic tumor volume (TMTV) measured on pretreatment F-18-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% SUVmax 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 = 43) had a 5-year PFS and OS of 43% and 46% compared with 76% and 78% for patients with a low TMTV (P = 0.0023, P = 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, PFS = 51%, OS = 55% BCL2, PFS = 49%, OS = 49% or DE PFS = 50%, OS = 50%) and a group with a good outcome (MYC, PFS = 93%, OS = 93% BCL2, PFS = 86%, OS = 86%, or DE PFS = 81%, OS = 81%). Conclusions: The combination of molecular and imaging characteristics at diagnosis could lead to a more accurate selection of patients, to increase tailor therapy. (C) 2016 AACR.