Abstract
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Objectives: Our aim was to study the prognostic value of two new FDG PET biomarkers in diffuse large B-cell lymphoma (DLBCL). The first one is the total tumor surface (TTS), describing the tumor-host interface. The second one is the tumor volume surface ratio (TVSR), corresponding to the ratio between the total metabolic tumor volume (TMTV) and TTS, describing the tumor fragmentation.
Methods: 215 patients with DLBCL were retrospectively included. The International Prognostic Index (IPI) was established. Patients underwent initial FDG PET/CT before R-CHOP (73%) or intensified R-CHOP (R-ACVBP) regimen (27%). TMTV was measured using a fixed threshold value of 41% of SUVmax for each lesion. Each surface was measured using an in-house ImageJ plugin based on the marching cubes algorithm. The total tumor surface (TTS) corresponding to the sum of the surfaces of all lesions was calculated, as well as TVSR, corresponding to the ratio between TMTV and TTS. To characterize the relationships between TMTV, TTS and TVSR, the Spearman’s rank correlation coefficient (r) was computed. Receiver operator characteristics (ROC) analysis was performed to determine the optimal TMTV and TVSR cut-off values. Survival functions at 5 years were estimated using a Kaplan-Meier method and were compared using a log rank test. Univariate and multivariate analysis were performed using a Cox proportional-hazards model. P-value was considered statistically significant if < 0.05 after Altman and Benjamini-Hochberg corrections.
Results: The median follow-up was 44 months. 5 y-PFS was 57% and 5 y-OS was 66%. TVSR was poorly correlated with TMTV (r= 0.5) and TTS (r=0.26), while TTS was highly correlated to TMTV (r=0.94). Thus TTS was excluded from the rest of the analysis. According to the ROC curve analysis, the optimal cut-off values to predict 5 y-OS were 222 cm3 for TMTV and 6.0 cm for TVSR. TMTV had the highest area under the ROC curve (AUC=0.711) and the best sensitivity (0.797), while TVRS had the best specificity (0.745) with an AUC=0.646. Patients with high TMTV and TVSR had significantly worse prognosis in Kaplan-Meier and Cox univariate analysis. In a multivariate Cox analysis combining IPI score, the type of chemotherapy, TMTV and TVRS, all tested parameters were independent and significant (p<0.05) prognostic factors (HR [95%CI]: IPI score 2.0 [1.1-3.4], type of chemotherapy 4.9 [2.2-11.2], TMTV 3.4 [1.8-6.2], TVSR 2.1 [1.30-3.3]) showing the added prognostic value of TVSR. Conclusions: These results show that the volume surface ratio of tumors measured on the initial FDG PET is an independent prognostic factor in DLBCL and has an additional prognostic value when combined with TMTV, IPI score and chemotherapy, while the total tumor surface is highly correlated to TMTV limiting its additional prognostic value.