Abstract
BACKGROUND: Tumor metabolic heterogeneity (MH) assessed by 18-fluorine fluorodeoxyglucose positron emission tomography computed tomography ((18)F-FDG PET/CT) is established as a marker of drug resistance in solid tumors. Its prognostic significance in diffuse large B-cell lymphoma (DLBCL) remains inadequately explored. This study aims to investigate the prognostic value of tumor MH assessed by (18)F-FDG PET/CT in DLBCL. METHODS: This study retrospectively included 297 patients diagnosed with DLBCL at the Third Affiliated Hospital of Soochow University from August 2012 to December 2022. We evaluated tumor MH using the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH). In addition to obtaining conventional PET metabolic metrics, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG), we also collected baseline clinical data. This study developed a survival prediction model based on Cox regression analysis and compared its prognostic performance with the National Comprehensive Cancer Network-International prognostic index (NCCN-IPI). We evaluated the model’s calibration, discrimination, and clinical utility, and conducted an internal validation. RESULTS: Multivariable Cox regression analysis indicated age (hazard ratio [HR], HR,1.62, 95% confidence interval [CI], 1.13 ~ 2.34, P = 0.01; HR, 2.15, 95% CI, 1.35 ~ 3.42, P = 0.001), TMTV (HR, 3.24, 95% CI, 1.56 ~ 6.73, P = 0.002; HR, 3.35, 95% CI, 1.30 ~ 8.62, P = 0.012), and AUC-CSH (HR, 0.64, 95% CI, 0.45 ~ 0.92, P = 0.015; HR, 0.59, 95% CI, 0.38 ~ 0.92, P = 0.018) as independent predictive factors for both progression-free survival (PFS) and overall survival (OS). Lower AUC-CSH value corresponded to higher tumor MH, indicating poorer survival outcome. The combined model outperformed the NCCN-IPI, achieving C-index of 0.688, 0.630 for PFS and 0.721, 0.688 for OS. The calibration curve showed good consistency, and the decision curve analysis (DCA) also confirmed its potential application value in individualized treatment decisions. CONCLUSIONS: Tumor MH, assessed by (18)F-FDG PET/CT, demonstrates potential as a prognostic biomarker in DLBCL. Its incorporation into predictive models may improve individualized prognostic evaluation and facilitate more precise treatment stratification for these patients. TRIAL REGISTRATION: This research has been retrospectively registered in the Ethics Committee institutional of the Third Affiliated Hospital of Soochow University [approval number (2022) KD155]. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-025-15149-x.