Tumor Location Relative to the Spleen Is a Prognostic Factor in Lymphoma Patients: A Demonstration from the REMARC Trial

Abstract

Baseline [ 18 F]FDG PET/CT radiomic features can improve the survival prediction in patients with diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate whether characterizing tumor locations relative to the spleen location in baseline [ 18 F]FDG PET/CT images predicts survival in patients with DLBCL and improves the predictive value of total metabolic tumor volume (TMTV) and ageadjusted international prognostic index (IPI). Methods: This retrospective study included 301 DLBCL patients from the REMARC (NCT01122472) cohort. Physicians delineated the tumor regions, whereas the spleen was automatically segmented using an openaccess artificial intelligence algorithm. We systematically measured the distance between the centroid of the spleen and all other lesions, defining the SD of these distances as the lesion spread (Spread-Spleen). We calculated the maximum distance between the spleen and another lesion (Dspleen) for each patient and normalized it with the body surface area, resulting in standardized Dspleen (sDspleen). The predictive value of each PET/CT feature for progression-free survival (PFS) and overall survival (OS) was evaluated through univariate and multivariate time-dependent Cox models and Kaplan-Meier analysis. Results: In total, 282 patients (mean age, 68.33 6 5.41 y; 164 men) were evaluated. The artificial intelligence algorithm successfully segmented the spleen in 96% of the patients. SpreadSpleen, Dspleen, and sDspleen were correlated neither with TMTV (Pearson r , 0.23) nor with IPI (Pearson r , 0.15). When median values were used as the cutoff, SpreadSpleen, Dspleen, and sDspleen all significantly classified patients into 2 risk groups for PFS and OS (P , 0.001). They complemented TMTV and IPI to classify the patients into 3 risk groups for PFS and OS (P , 0.001). Integrating SpreadSpleen, Dspleen, or sDspleen into a Cox model on the basis of TMTV, IPI, and TMTV combined with IPI significantly improved the concordance index for PFS and OS (P , 0.05). Conclusion: Baseline PET/CT features that characterize tumor spread and dissemination relative to the spleen strongly predicted survival in patients with DLBCL. Integrating these features with TMTV and IPI further improved survival prediction.