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

Clin Cancer Res. 2016 Aug 1;22(15):3801-9. doi: 10.1158/1078-0432.CCR-15-2825. Epub 2016 Mar 2.

Abstract

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% 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. Clin Cancer Res; 22(15); 3801-9. ©2016 AACR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor*
  • Female
  • Fluorodeoxyglucose F18*
  • Gene Expression Profiling* / methods
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Positron Emission Tomography Computed Tomography* / methods
  • ROC Curve
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Burden
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Fluorodeoxyglucose F18