Metabolic Biomarkers Assessed with PET/CT Predict Sex-Specific Longitudinal Outcomes in Patients with Diffuse Large B-Cell Lymphoma

SIMPLE SUMMARY: There is a sex disparity in lymphoma where males have higher incidence and mortality compared to females. Sex differences in metabolism may be a significant factor underlying this phenomenon where visceral obesity, a known biomarker for poor outcomes in multiple pathophysiological states, is higher in males compared to females. Here, we report that visceral fat, although higher in males with diffuse large B-cell lymphoma (DLBCL), selectively predicted worse outcomes in females. Moreover, females that selectively gained visceral fat during chemotherapy did worse, and combining the change in visceral fat over the course of chemotherapy and tumor glucose uptake measured by FDG-PET at end of treatment identified a subgroup of females with extremely poor outcomes. ABSTRACT: In many cancers, including lymphoma, males have higher incidence and mortality than females. Emerging evidence demonstrates that one mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. We wanted to determine if visceral fat and tumor glucose uptake with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could predict sex-dependent outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis of 160 patients (84 males; 76 females) with DLBCL who had imaging at initial staging and after completion of therapy. CT-based relative visceral fat area (rVFA), PET-based SUVmax normalized to lean body mass (SULmax), and end-of-treatment FDG-PET 5PS score were calculated. Increased rVFA at initial staging was an independent predictor of poor OS only in females. At the end of therapy, increase in visceral fat was a significant predictor of poor survival only in females. Combining the change in rVFA and 5PS scores identified a subgroup of females with visceral fat gain and high 5PS with exceptionally poor outcomes. These data suggest that visceral fat and tumor FDG uptake can predict outcomes in DLBCL patients in a sex-specific fashion.