Interim positron emission tomography scan associated with international prognostic index and germinal center B cell-like signature as prognostic index in diffuse large B-cell lymphoma

Abstract

[(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is essential to optimize the initial staging and to predict the prognosis of diffuse large B-cell lymphoma (DLBCL). To assess the relationship between the germinal center B cell-like/activated B cell-like (GCB/ABC) classification and PET scan features in DLBCL, 57 cases treated with rituximab and a cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)/CHOP-like regimen were analyzed. The expression profile of 18 GCB/ABC related genes and five genes coding for glucose transporters (GLUTs) was determined from frozen tissues using DASL (cDNA-mediated Annealing, Selection, Ligation and extension) technology. According to the gene expression profile (GEP), 30 cases of DLBCL were classified as GCB subtype (2-year progression-free survival [PFS] 76%) and 27 cases as ABC subtype (2-year PFS 51%, p = 0.03). Using a semiquantitative assessment of the decrease in standard uptake value (SUV) at interim PET performed after 3-4 cycles of chemotherapy, we defined fast (n = 36) and slow (n = 9) metabolic responders. In multivariate analysis, GCB/ABC subtype, age-adjusted international prognostic index (aaIPI) and slow/fast metabolic response were independent variables that predicted outcome. A score incorporating aaIPI, fast/slow metabolic response and GCB/ABC classification was used to define two groups with highly significantly distinct outcomes. Our study suggests that the combination of GEP, aaIPI and interim PET more accurately predicts DLBCL prognosis and is therefore suitable for tailoring therapeutic strategies.

Imaging genomics in cancer research: limitations and promises

“…11 (29%) studies used semiautomatic image feature extraction. 45 28,47,48,50,51,55,57,59,61,63,[69][70][71]79 Only four studies correlated with histology. 50,60,71,74 None of the study verified their results via wet-lab techniques.…”

“…The type and distribution of cancers in these studies were similar to those for radiogenomic studies, except for two studies that focused on low-grade glioma 47,58 and one study that focused on diffuse large B-cell lymphoma. 59 The imaging modalities used included CT (n 5 9), MRI (n 5 21, including five perfusion) and PET (n 5 6). Two studies used both CT and MR. 46,53 The number of imaging features extracted ranged from 1 to 120 with a median of 5.…”

Somatic mutations of cell-free circulating DNA detected by next-generation sequencing reflect the genetic changes in both germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphomas at the time of diagnosis

“…The cellof-origin signature was determined by cDNA-mediated annealing, selection, extension, and ligation technology based on the expression of 19 genes, as previously reported. 10 Among the 12 cases analyzed, five belonged to the ABC subgroup, six to the GCB subgroup and one case was unclassified (Table 1).…”

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

“…According to the GEP, patients were classified as GCB or ABC subtype, as previously reported (21). MYC and BCL2 mRNA expression were also determined by DASL technology.…”

“…Therefore molecular data, even if they are not used routinely, are potentially predictive biomarkers. The combination between these two prognosticators, FDG-PET/CT and gene expression profiling, has been recently investigated and our group has suggested that the response to treatment evaluated by interim PET combined with molecular profile could gain some interest in risk stratification (21).…”