Association between Abdominal Adiposity, Muscle Mass, and Metabolic Syndrome in Survivors of Testicular Germ Cell Cancer Kyaw Z. Thein, MD 1,3, William Osai, NP-C 1, Shi-Ming Tu, MD 1, Lance C. Pagliaro, MD 2, Jeri Kim, MD 1, Sai-Ching J Yeung, MD, PhD 1   1The University of Texas MD Anderson Cancer Center, 2Mayo Clinic, 3Texas Tech University Health Sciences Center BACKGROUND Effective therapies have resulted in an increased number of cancer survivors, and it is estimated that cancer survivors will approach 20 million by 2020. Cancer and cancer therapy effects linger long after treatment. In the United States, testicular germ cell tumor (TGCT) is the predominate type of germ cell tumors, and it has a high incidence in men 19 to 39 years old. Cisplatin-based chemotherapy and radiation therapy offer an excellent cure rate approaching 100% for early stage disease. Because of their relative young age at diagnosis, TGCT survivors contend with treatment effects for decades after treatment. Several studies have documented the long-term adverse effects of testicular cancer treatment, including increased risk of cardiac disease and mortality after chemotherapy, radiation, or a combination of both; abnormal lipid metabolism; risk of excessive body mass index (BMI) increase; and increased risk of metabolic syndrome (MTS). Because reliably predicting MTS could prompt intervention reducing risk, we analyzed clinical data and body composition in computed tomography (CT) scans to identify associations. METHODS This retrospective study was submitted to the institutional review board of The University of Texas MD Anderson Cancer Center in accordance with institutional policies, and no informed consent was required for this chart review study. In a retrospective review of the charts of 196 TGCT survivors treated at a single institution from 1970 to 2007, we collected patient demographics, clinical data, body fat composition measures, and evidence from CT scans from baseline through posttreatment. NIH Image J was used to analyze cross-sectional CT images and measure subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle. Visceral fat-to-muscle ratio (VMR), visceral-to-subcutaneous fat ratio (VSR), and change in VMR and VSR from baseline to 3 to 5 years posttreatment (ΔVMR and ΔVSR) were calculated.  We also gathered measures of posttreatment glucose, blood pressure, lipid data, and body weight and height at time of scans.  The 2001 U.S. National Cholesterol Education Program Adult Treatment Panel III guideline defined MTS. Using univariate and multivariate logistic regression analyses, we identified associations.   Excluded were patients who were treated with orchiectomy only without chemotherapy or radiation therapy; patients with incomplete records; and patients who expired. RESULTS/DISCUSSION Of the 167 patients included in the final analysis, 37.7% had MTS, 76.6% were white, and 68.9% had chemotherapy.  Patients with MTS had significantly higher VMRs (p = .007) and VSRs (p = .021) than those without.  Patients who received chemotherapy and radiotherapy were significantly more likely to have MTS (p = .044 and p = .037) than others.   A multinomial logistic regression model that included year of cancer diagnosis, age, race, tumor histology, treatment types, VSR, and VMR confirmed the association of high VMR and VSR with future development of MTS. In a similar regression model, ΔVMR and ΔVSR were not statistically significant predictors.   Exercise and physical activity aimed at decreasing VMR and VSR may help lower incidence of MTS in patients with TGCT. Figure 1. Analyzing VMR, VSR from total fat area, subcutaneous fat area, visceral fat area, and total muscle area using NIH image J. Table 2. Demographics and other characteristics of patients Characteristics Total number (n) Metabolic syndrome 76 Seminoma 58 Nonseminoma 129 Others 9 REFERENCES ASCO Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors. (2007). J Oncol Prac, 3(4), 233-235. Dearnaley et al. (2001). Managing Testicular Cancer (Vol. 322). DeSantis et al. (2014). CA Cancer J Clin, 64(4), 252-271. Fosså et al. (2007). J Natl Cancer Inst, 99(7), 533-544. Grundy et al. (2004). Arterioscler Thromb Vasc Biol, 24(8), e149-e161. Haugnes et al. (2010). J Clin Oncol, 28(30), 4649-4657. Huddart et al. (2003). Am J Cancer, 2(5), 325-334. Koc et al. (2011). 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OBJECTIVES The objectives of this retrospective study are: To determine the prevalence of MTS in patients with testicular germ cell tumors after treatment with a cisplatin-based chemotherapy To identify characteristics prognostic of development of MTS in patients who have been treated with a cisplatin-based chemotherapy for testicular germ cell tumors To determine association between abdominal adiposity, chemotherapy, and MTS in patients with testicular germ cell tumors after undergoing cisplatin-based chemotherapy Characteristics P value Age 0.361 Race 0.509 Chemotherapy 0.046 Radiation therapy 0.031 Visceral fat-to-muscle ratio (VMR) 0.007 Visceral-to-subcutaneous fat ratio (VSR) 0.021 Change in VMR (ΔVMR) NS Change in VSR (ΔVSR) Table 1. Chemotherapy regimens used for testicular cancer at MD Anderson Cancer Center CISCA Dose in mg/m2/day Cyclophosphamide days 1 and 2 Doxorubicin days 1 and 2 Cisplatin day 3 VB Vinblastine days 22 to 26 Bleomycin days 22 to 26 400   35 100     2.5 25 U/day BEP Bleomycin days 1, 8, and 15 Etoposide days 1-5 Cisplatin days 1-5 30 U/day   20 Corresponding Author : kyaw.z.thein@ttuhsc.edu. Presented at ASCO Palliative Care in Oncology Symposium, 2016.