A nomogram for predicting the rapid progression of diffuse large B‐cell lymphoma established by combining baseline PET/CT total metabolic tumor volume, lesion diffusion, and TP53 mutations

Abstract

ObjectivesThis study aimed to integrate positron emission tomography/computed tomography (PET/CT) metrics and genetic mutations to optimize the risk stratification for diffuse large B‐cell lymphoma (DLBCL) patients.MethodsThe data of 94 primary DLBCL patients with baseline PET/CT examination completed in the Shandong Cancer Hospital and Institute (Jinan, China) were analyzed to establish a training cohort. An independent cohort of 45 DLBCL patients with baseline PET/CT examination from other hospitals was established for external validation. The baseline total metabolic tumor volume (TMTV) and the largest distance between two lesions (Dmax) standardized by patient body surface area (SDmax) were calculated. The pretreatment pathological tissues of all patients were sequenced by a lymphopanel including 43 genes.ResultsThe optimal TMTV cutoff was 285.3 cm3 and the optimal SDmax cutoff was 0.135 m−1. TP53 status was found as an independent predictive factor significantly affecting complete remission (p = 0.001). TMTV, SDmax, and TP53 status were the main factors of the nomogram and could stratify the patients into four distinct subgroups based on their predicted progression‐free survival (PFS). The calibration curve demonstrated satisfactory agreement between the predicted and actual 1‐year PFS of the patients. The receiver operating characteristic curves showed this nomogram based on PET/CT metrics and TP53 mutations had a better predictive ability than the clinic risk scores. Similar results were identified upon external validation.ConclusionsThe nomogram based on imaging factors and TP53 mutations could lead to a more accurate selection of DLBCL patients with rapid progression, to increase tailor therapy.

Biological signatures of the International Prognostic Index in diffuse large B-cell lymphoma

“… 30 , 31 Of note, TP53 Mut was an independent prognostic factor of PFS and OS, representing a distinct subtype with inferior prognosis irrespective of IPI score. 5 , 32 Less likely to benefit from R-CHOP–based immunochemotherapy, 33 , 34 , 35 novel targeted therapies, such as decitabine, 19 are required for patients with TP53 Mut , even stratified as low-risk IPI. Furthermore, our study demonstrated that integrating TP53 Mut into the IPI enhanced its capacity to differentiate patient survival outcomes, which has also been validated by external cohorts.…”

Molecular Subtypes and the Role of TP53 in Diffuse Large B-Cell Lymphoma and Richter Syndrome

“…Taking the above into consideration, novel predictive scores are being established that include TP53 abnormalities in combination with other biological and clinical markers. In one study, PET/CT data from DLBCL patients and a targeted NGS panel consisting of 43 commonly mutated genes were employed to devise a prognostic score [ 117 ]. Among the different variables, the pretreatment total metabolic tumor volume, the largest distance between two lesions standardized by body area, and the presence of TP53 mutations emerged as the most important factors for risk stratification and inferior PFS, displaying better accuracy than current clinical scores.…”