Combination of baseline PET/CT total metabolic tumor volume, lesion dissemination and TP53 mutations predicts rapid progression of diffuse large B-cell lymphoma

Abstract

Background: The existing International Prognostic Index (IPI) scoring system has failed to fully identify high risk population for diffuse large B-cell lymphoma (DLBCL). The next-generation prognosis model may combine PET scanning indicators, total metabolic tumor volume (TMTV) or the largest distance between 2 lesions (Dmax) normalized with the body surface area [standardized Dmax (SDmax)], and genetic mutations to identify high-risk patients early. Methods: We analyzed 93 patients with DLBCL treated with rituximab and CHOP/CHOP-like regimen. TMTV was calculated using the 41% maximum standardized uptake value thresholding method. From the 3D coordinates, the centroid of each lesion was automatically obtained and considered as the lesion location; Dmax was calculated and normalized by patient body surface area (BSA), given by √(weight x height)36 00, yielding SDmax. The pathological tissues of all patients before treatment were sequenced by a lymphopanel to identify mutations in 43 genes. Results: The optimal TMTV cutoff was 210.1 cm3, and the optimal SDmax cutoff was 0.146 m-1. In multivariate analysis, high SDmax, high TMTV and A53-like subtype were independent prognostic factors of PFS (P=0.047, 0.035 and 0.031, respectively). TMTV or SDmax combined with TP53 mutations can identify significant risk stratification in patients. TMTV combined with TP53 mutations identified 3 groups with a significant difference in PFS (P=0.003): 42 patients with low TMTV regardless of TP53 status; 36 with high TMTV and wild-type TP53; and 15 with high TMTV and mutant TP53. In the three groups, 1-year PFS was 81.4%, 55.4% and 38.9%, respectively. SDmax combined with TP53 mutations also identified 3 groups with a significant difference in PFS (P < 0.001), and 1-year PFS was 84.8%, 58.3% and 32.0%, respectively. Conclusions: In patients with low tumor burden or without distant metastasis, gene mutations seems to have little effect on prognosis. While in patients with heavy load, combination of TMTV or SDmax with TP53 mutations could lead to more accurate selection and better individualized treatment. Based on this study, we suggest that next-generation sequencing should be carried out in the newly diagnosed patients with heavy tumor load or distant metastasis in the future, so as to further distinguish the high-risk patients and guide the treatment.