McGree, Michaela

Abstract Obesity accelerates the onset and progression of age-related conditions. In preclinical models, obesity drives cellular senescence, a cell fate that compromises tissue health and function, in part through a robust and diverse secretome. In humans, components of the secretome have been used as senescence biomarkers that are predictive of age-related disease, disability, and mortality. Here, using biospecimens and clinical data from two large and independent cohorts of older adults, we tested the hypothesis that the circulating concentrations of senescence biomarkers are influenced by body mass index. After adjusting for age, sex, and race, we observed significant increases in activin A, Fas, MDC, PAI1, PARC, TNFR1, and VEGFA, and a significant decrease in RAGE, from normal weight, to overweight, to obesity body mass index categories by linear regression in both cohorts (all p < .05). These results highlight the influence of body mass index on circulating concentrations of senescence biomarkers.

We investigated the impact of sarcopenia on adjuvant chemotherapy dosing in advanced epithelial ovarian cancer (EOC). The chemotherapy dosing and toxicity of 173 eligible patients who underwent cytoreductive surgery and adjuvant chemotherapy at a single institution were analyzed. Patients with a skeletal muscle index less than 39 cm2/m2 measured on a CT scan were considered sarcopenic. Sarcopenic and non-sarcopenic patients were compared with regard to relative dose intensity (RDI), completion of scheduled chemotherapy, toxicity, and survival. A total of 62 (35.8%) women were sarcopenic. Sarcopenic women were less likely to complete at least six cycles of chemotherapy (83.9% vs. 95.5%, p = 0.02). The mean RDI for both carboplatin (80.4% vs. 89.4%, p = 0.03) and paclitaxel (91.9% vs. 104.1%, p = 0.03) was lower in sarcopenic patients compared to non-sarcopenic patients. Despite these differences in chemotherapy, there was no difference in neutropenia or median overall survival (3.99 vs. 4.57 years, p = 0.62) between the sarcopenic and non-sarcopenic women, respectively. This study highlights the importance of considering lean body mass instead of body weight or surface area in chemotherapy dosing formulas for sarcopenic women with advanced EOC. Further research is needed to optimize chemotherapy strategies based on individual body composition, potentially leading to improved dosing strategies in this population.

Objectives To study the association between multi-morbidity percentiles, which is a measure of clinical aging, and interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α. Methods Participants 50 to 95 years of age from the Mayo Clinic Study of Aging were assigned age- and sex-specific multi-morbidity percentiles using look-up tables that were reported previously (n = 1646). Percentiles were divided into quintiles for analysis. Plasma IL-6, IL-10, and TNF-α levels were measured in 1595 participants. Median inflammatory marker levels were compared across multi-morbidity quintiles using nonparametric tests. Results People with higher multi-morbidity percentiles had significantly higher IL-6 and TNF-α levels compared with those with lower multi-morbidity percentiles. Tests for trend across five multi-morbidity quintiles were significant among women for IL-6 and among participants 70 years of age or older for IL-6 and TNF-α. IL-10 was not associated with multi-morbidity percentiles. Conclusions Multi-morbidity percentiles may be a useful clinical index of biological age for future studies, particularly in women and people 70 years of age and older.

5577 Background: Perioperative red blood cell transfusion (PRBCT) may be a negative prognostic marker in surgical oncology. We assessed PRBCT as an independent risk factor for recurrence and death from epithelial ovarian cancer (EOC) in the largest cohort to date. Methods: Patient characteristics and process-of-care variables (NSQIP-defined, >130 variables) were retrospectively abstracted from 587 women who underwent primary staging and cytoreduction for EOC (1/1/03-12/29/08). Evaluated using propensity scoring with univariate logistic regression and odds ratios (OR) and Cox proportional hazards regression and hazard ratios (HR). Factors with p<0.1 used in multivariate models. Results: Rate of PRBCT was 77.0% (452/587). In univariable analysis, PRBCT was associated with older age (OR 1.25[95% CI 1.06, 1.48]/10yr increase), stage≥IIIa (4.66[3.04, 7.13]), splenectomy (26.63[3.67, 193.17]), higher surgical complexity (1.86[1.17, 2.95] score 2; 21.48 [7.37, 62.59] 3; referent 1), serous histology (2.36[1.57, 3.55]vs non-serous), longer operating time (1.58[1.36, 1.83]/hr increase), and residual disease (3.26[1.97, 5.41]≤1cm; 1.97[1.09, 3.56]>1cm), and lower preop hemoglobin (Hb) (1.89[1.59, 2.27]per 1g/dL decrease). In univariable analysis, PRBCT was associated with a higher risk of recurrence (HR 1.96[95% CI 1.43, 2.68]) and death (1.71[1.28, 2.28]). However, in multivariable analysis, stage≥IIIa (4.03[2.05, 6.49]), splenectomy (1.41[1.02, 1.95]), residual disease (1.86[1.41, 2.46]≤1cm; 2.91[2.02, 4.18]>1cm), and lower preop Hb (1.09[1.01, 1.19]) were associated with higher risk of recurrence. Older age (1.24[1.12, 1.37]), stage≥IIIa (3.07[1.93, 4.90]), albumin ≤3 g/dL (2.06[1.28, 3.31]), residual disease (1.63[1.22, 2.19]≤1cm; 3.03[2.19, 4.18]>1cm), and low Hb (1.08[1.00, 1.19]) were associated with higher risk of death. Serous histology (0.70[0.52, 0.95]) associated with lower risk of death. Conclusions: PRBCT does not appear to be directly associated with disease-free and overall survival in EOC. Lower preoperative Hb was associated with a higher risk of both recurrence and death. The need for PRBCT appears to be a stronger prognostic indicator than the receipt of PRBCT.

5004 Background: Since 1999, patients with low-risk endometrial cancer (EC) as defined by the Mayo criteria have preferably not undergone lymphadenectomy (LND) at our institution. We assess survival, sites of recurrence, morbidity, and cost per up-staged case in this low-risk cohort. Methods: Consecutive patients with Mayo-defined low-risk EC managed without (non-LND) and with LND were compared. Cause-specific survival (CSS) was estimated using the Kaplan-Meier method and compared using the log-rank test. 30-day cost analyses were equated to 2010 Medicare dollars. Results: Among 1,393 consecutive surgically managed EC cases, 385 (27.6%) met the Mayo low-risk criteria, accounting for 34.1% of type I EC. The 5-year CSS of the low-risk cases was 98.6 %. There were 80 LND cases (median # nodes, 29) and 305 non-LND cases. Complications within 30 days occurred in 37.5% and 19.3% of LND and non-LND cases, respectively (P<0.001). Nodal metastasis was identified in a single LND case (1.3%). There were 11 recurrences, 6 of which were vaginal. Not a single recurrence was detected in the pelvic or paraaortic nodal areas in these 385 patients, with a median follow-up of 5.4 years. The estimated prevalence (combining surgery and surveillance) of lymph node metastasis was 0.3%. The 5-year CSS in LND and non-LND cases was 97.3% and 99.0%, respectively (P=0.32). Patients were more than seven times as likely to die of co-morbidities than from EC. The 30-day median cost of care was $15,678 for LND cases compared to $11,028 for non-LND cases (P<0.001). The estimated cost per up-staged low-risk case was $439,990 if performed via endoscopy and $327,866 via laparotomy. If the 305 non-LND cases had been subjected to LND, an estimated additional $1,418,189 would have been expended. Conclusions: For patients with low-risk EC as defined by the Mayo criteria, lymphadenectomy dramatically increases morbidity and 30-day cost of care without discernible short- or long-term benefits: CSS was 99% with a 0.3% rate of nodal metastasis. In these low-risk patients, hysterectomy with salpingo-oophorectomy alone is appropriate surgical management and should be standard of care.