Longitudinal assessment of prognostic sex differences in lymphoma patient metabolism using PET/CT

621 Objectives: A sex disparity is noted in many cancers where men have higher incidence and mortality compared to women. We recently identified that sex differences in tumor glucose metabolism and patient metabolism, measured by visceral obesity, can stratify patients on a sex specific basis (PMID: 29558292, 28768910). Because of known differences in outcomes in diffuse large B-cell lymphomas (DLBCL) where men have poorer outcomes compared to women, we sought to evaluate the prognostic value of sex differences in metabolism using (i) visceral obesity measured with CT, (ii) tumor glucose uptake measured with FDG-PET, and (iii) fasting serum glucose (BG) in patients with DLBCL over the course of therapy. Methods: This retrospective study analyzed patients diagnosed with de novo DLBCL between May 2007 and May 2015 who were treated at Washington University in St. Louis and received initial staging and subsequent, interim and completion of therapy, PET/CT scans. Those with transformed DLBCL, primary CNS lymphoma, primary mediastinal B-cell lymphoma, intravascular lymphoma, gray zone lymphoma, post-transplant lymphoproliferative disease, active secondary malignancy, or concurrent HIV were excluded. CT datasets were used to obtain the normalized relative visceral fat area at the level of the umbilicus (rVFA). Maximum standard uptake values corrected for lean body mass (SULmax) were calculated for initial staging and subsequent FDG PET/CT scans. Progression free survival (PFS) was defined as the time from diagnosis to relapse of disease or initiation of salvage therapy. Overall survival (OS) was defined as time from diagnosis to death from disease. Patients were followed up for a median of 34.5 months. Optimized thresholds for identifying maximum sex differences in PFS and OS were calculated as previously published (PMID: 23251644). Results: 161 patients were identified (77M, 84F). Median OS and PFS for the whole cohort were not reached. Sex differences were identified with lean body mass (LBM) where males with LBM >62.6 had significantly improved PFS (7 relapses of 46 males) compared with LBM 37.5% had significantly shorter PFS (8 relapses of 22 females) compared to rVFA 98.5 mg/dL) and completion of therapy (>110 mg/dL) mirrored the female-specific survival effects of rVFA and was significant only in females (p=0.03 and p=0.005 respectively). SULmax identified discordant sex differences in survival at initial staging. Males with SULmax >14.5 unexpectedly had better PFS than males with SULmax 17.5 had shorter PFS compared to females with SULmax 7.6 had a median PFS of 12 months versus 86 months for the remainder of males (p=2e-9). Similarly, females with SULmax >2.96 had a significantly poorer median PFS of 7.2 months versus an undefined median PFS for the remainder of females (p=4e-6). The deltaSULmax between completion of therapy and initial staging revealed the most significant sex differences in the analysis. Males with a deltaSULmax >59.5% had a better median PFS (85.3 months) compared with the remainder of males (median PFS 7.7 months, p=1.5e-5). In contrast, female stratification was marginally significant (Figure 1). Conclusions: In summary, LBM selectively stratifies males and rVFA selectively stratifies females with DLBCL. There are robust male-specific effects of chemotherapy on tumor metabolism and patient survival, as identified with delta SULmax. Sex differences in tumor and patient metabolism can be used to better predict outcomes and response to therapy.