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

Anne-Ségolène Cottereau, Hélène Lanic, Sylvain Mareschal, Michel Meignan, Pierre Vera, Hervé Tilly, Fabrice Jardin, Stéphanie Becker

The prognostic impact of total metabolic tumor volume (TMTV) measured on pretreatment 18F-FDG PET/CT and its added value to molecular characteristics was investigated in patients with diffuse large B-cell lymphoma (DLBCL). For 81 newly diagnosed DLBCL patients, 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 GCB or ABC subtypes and MYC or BCL2 overexpressed. Median follow-up was 64 months. 5y-PFS and OS were 60% and 63% in the whole population. Median pre-therapy TMTV was 320 cm3 (25th-75th percentiles 106-668 cm3). With a 300cm3cut off, patients with high TMTV (n=43) had a 5 y-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 sub-stratification 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%). The combination of molecular and imaging characteristics at diagnosis could lead to a more accurate selection of patients, in order to increase tailor therapy.