Prognostic value of metabolic tumour volume on baseline ${}^{18}$F-FDG PET/CT in addition to NCCN-IPI in patients with diffuse large B-cell lymphoma: further stratification of the group with a high-risk NCCN-IPI

The purpose of this study was to determine the prognostic value of metabolic volumetric parameters as a quantitative index on pre-treatment ${}^{18}$F-FDG PET/CT in addition to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL). A total of 103 consecutive patients with DLBCL and baseline FDG PET/CT were retrospectively evaluated. Quantitative metabolic parameters, including total metabolic tumour volume (TMTV) using a standardized uptake value (SUV) of ≥2.5 as the threshold, were estimated. Receiver operating characteristic curve analysis was used to determine the optimal cut-off values for the metabolic parameters. The relationships between study variables and patient survival were tested using Cox regression analysis. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. Median follow-up was 34 months. In patients with a low TMTV (<249 cm${}^3$), the 3-year progression free survival (PFS) rate was 83% and the overall survival (OS) rate was 92%, in contrast to 41% and 57%, respectively, in those with a high TMTV (≥249 cm${}^3$). In univariate analysis, a high TMTV and NCCN-IPI ≥4 were associated with inferior PFS and OS (P < 0.0001 for all), as was a high total lesion glycolysis (P = 0.004 and P = 0.005, respectively). In multivariate analysis, TMTV and NCCN-IPI were independent predictors of PFS (hazard ratio, HR, 3.11, 95% confidence interval, CI, 1.37–7.07, P = 0.007, and HR 3.42, 95% CI 1.36–8.59, P = 0.009, respectively) and OS (HR 3.41, 95% CI 1.24–9.38, P = 0.017, and HR 5.06, 95% CI 1.46–17.60, P = 0.014, respectively). TMTV was able to separate patients with a high-risk NCCN-IPI of ≥4 (n = 62) into two groups with significantly different outcomes; patients with low TMTV (n = 16) had a 3-year PFS rate of 75% and an OS rate of 88%, while those with a high TMTV had a 3-year PFS rate of 32% and an OS rate of 47% (χ${}^2$ = 7.92, P = 0.005, and χ${}^2$ = 8.26, P = 0.004, respectively). However, regardless of TMTV, patients with a low-risk NCCN-IPI of <4 (n = 41) had excellent outcomes (3-year PFS and OS rates of 85% and 95%, respectively). Pretreatment TMTV was an independent predictor of survival in patients with DLBCL. Importantly, TMTV had an additive prognostic value in patients with a high-risk NCCN-IPI. Thus, the combination of baseline TMTV with NCCN-IPI may improve the prognostication and may be helpful guide the decision for intensive therapy and clinical trials, especially in DLBCL patients with a high-risk NCCN-IPI.