Value of total lesion glycolysis and cell-of-origin subtypes for prognostic stratification of diffuse large B-cell lymphoma patients

Abstract

Background: This study aimed to explore the added prognostic value of baseline metabolic volumetric parameters and cell of origin subtypes to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in nodal diffuse large B-cell lymphoma (DLBCL) patients.

Methods: A total of 184 consecutive de novo nodal DLBCL patients who underwent baseline positron emission tomography/computed tomography (PET/CT) were included in this study. Kaplan-Meier estimates were generated to evaluate the clinical, biological, and PET/CT parameters' prognostic value. The Cox proportional hazards model was performed to examine the potential independent predictors for progression-free survival (PFS) and overall survival (OS).

Results: With a median follow-up of 35 months, the 3-year PFS and OS were 65.2% and 73.0%, respectively. In univariate analysis, total lesion glycolysis (TLG), cell-of-origin subtypes, and NCCN-IPI were both PFS and OS predictors. High TLG (≥1,852), non-germinal center B (non-GCB), as well as high NCCN-IPI (≥4), were shown to be independently significantly associated with inferior PFS and OS after multivariate analysis. Based on the number of risk factors (high TLG, non-GCB, and high NCCN-IPI), a revised risk model was designed, and the participants were divided into four risk groups with very different outcomes, in which the PFS rates were 89.7%, 66.2%, 51.7%, and 26.7% (χ²=30.179, P<0.001), and OS rates were 93.1%, 73.8%, 56.7%, and 43.3%, respectively (χ²=23.649, P<0.001), respectively. Compared with the NCCN-IPI alone, the revised risk model showed a stronger ability to reveal further discrimination among subgroups, especially for participants with very unfavorable survival outcomes (PFS: χ²=9.963, P=0.002; OS: χ²=4.166, P=0.041, respectively).

Conclusions: The TLG, cell-of-origin subtypes, and NCCN-IPI are independent prognostic survival factors in DLBCL patients. Moreover, the revised risk model composed of the number of risk factors (high TLG, non-GCB, and high NCCN-IPI) can stratify patients better than the NCCN-IPI, especially for patients at high risk, which suggests its potential integration into decision making for personalized medicine.

Keywords: National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI); Total lesion glycolysis (TLG); cell-of-origin; diffuse large B-cell lymphoma (DLBCL); prognosis.

Figure 1

Flow chart of participant selection.

Figure 2

Kaplan-Meier curves for PFS and OS based on TLG (<1,852 vs. ≥1,852), cell of origin and NCCN-IPI. (A,B) PFS (A) and OS (B) estimated using TLG; (C,D) PFS (C), and OS (D) estimated using the cell of origin; (E,F) PFS (E) and OS (F) estimated using the NCCN-IPI. PFS, progression-free survival; OS, overall survival; TLG, total lesion glycolysis; NCCN-IPI, National Comprehensive Cancer Network International Prognostic Index.

Figure 3

Revised risk model based on TLG, cell of origin and NCCN-IPI. (A) Illustration of the revised risk model using maximal intensity projection on ¹⁸F-FDG PET images. (B) Illustration participant distribution between the NCCN-IPI and the revised risk model. (C,D) Kaplan-Meier curves for PFS (C) and OS (D) in all participants estimated using NCCN-IPI. (E,F) Kaplan-Meier curves for PFS (E) and OS (F) estimated using the revised risk model. TLG, total lesion glycolysis; NCCN-IPI, National Comprehensive Cancer Network International Prognostic Index; ¹⁸F-FDG, fluorine-18-fluorodeoxyglucose; PFS, progression-free survival; OS, overall survival.

Figure 4

Kaplan-Meier curves for PFS and OS with the revised risk model in relation to age subgroups (≤60 and >60 years old). (A,B) PFS (A) and OS (B) in relation to the ≤60 years old group; (C,D) PFS (C) and OS (D) in relation to the >60 years old group. PFS, progression-free survival; OS, overall survival.