Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) enter hibernation as a survival strategy during extreme environmental conditions. Typical ground squirrel hibernation is characterized by prolonged periods of torpor with significantly reduced heart rate, blood pressure, and blood flow, interrupted every few weeks by brief interbout arousals (IBA) during which blood flow fluctuates dramatically. These physiological conditions should increase the risk of stasisinduced blood clots and myocardial ischemia. However, ground squirrels have adapted to survive repeated bouts of torpor and IBA without forming lethal blood clots or sustaining lethal ischemic myocardial damage. The purpose of this study was to determine if ground squirrels are resistant to thrombosis and myocardial ischemia during hibernation. Blood markers of coagulation, fibrinolysis, thrombosis, and ischemia, as well as histological markers of myocardial ischemia were measured throughout the annual hibernation cycle. Hibernating ground squirrels were also treated with isoprenaline to induce myocardial ischemia. Thrombin-antithrombin complex levels were significantly reduced (p < 0.05) during hibernation, while D-dimer level remained unchanged throughout the annual cycle both consistent with an antithrombotic state. During torpor the ground squirrels were in a hyperfibrinolytic state with an elevated ratio of tissue plasminogen activator complexed with plasminogen activator inhibitor to total plasminogen activator inhibitor (p < 0.05). Histological markers of myocardial ischemia were reversibly elevated during hibernation with no increase in markers of myocardial cell death in the blood. These data suggest that ground squirrels do not form major blood clots during hibernation through suppression of coagulation and a hyperfibrinolytic state. These animals also demonstrate myocardial resistance to ischemia.
5568 Background: Nearly 50% of patients with high grade ovarian cancer (HGOC) harbor a germline or somatic mutation in BRCA1/BRCA2 or have tumors characterized by homologous recombination deficiency (HRD). HRD is associated with response to poly(ADP-ribose) polymerase inhibitors (PARPi) in HGOC. Although PARPi show great promise, there is interest in investigating how HRD status affects outcomes and can be used to objectively tailor other treatment strategies. We aimed to compare clinical and survival outcomes in HGOC stratified by HRD status. Methods: We performed a retrospective analysis of all advanced HGOC from April 2013 to June 2019. Patients were included if germline BRCA and HRD status was known. Clinical outcomes were analyzed and stratified by (1) germline BRCA+ (2) germline BRCA - and somatic BRCA/HRD+, or (3) BRCA-/HRD-. Progression free (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods stratified by HRD status and modeled via Cox proportional hazards regression. Results: 1271 patients with advanced HGOC presented during the study period of which 187 met inclusion criteria. 106 patients had germline BRCA mutation, 26 somatic BRCA/HRD+, and 55 BRCA/HRD-. Patients who had HRD- tumor had older median age at diagnosis (63 vs. 54 and 60 years, p<0.001), white race (89% vs. 74% and 68%), non-serous histology (20% vs. 6% and 0%, p=0.04), required more NACT chemotherapy cycles (4 vs. 3 and 3 cycles, p=0.03), and less complete gross resection (R0) at tumor reductive surgery (TRS) (60% vs. 83% and 77%, p=0.02). Patients who had BRCA/HRD- tumor had worse PFS (14.9 months) compared to germline BRCA+ (23.5 months) or somatic BRCA/HRD+ (20.2 months, p<0.001). Patients with BRCA/HRD- disease also had worse OS (42.3 months) compared to germline BRCA+ (68.8 months) or somatic BRCA/HRD+ (69.2 months). Multivariate analysis for PFS revealed that age (HR 1.02, 95% CI 1.00-1.04), p=0.01), stage (HR 5.7, 95% CI 1.39-23.4, p=0.02), R0 resection at TRS (HR 0.41, 95% CI 0.21-0.83, p=0.01), and BRCA/HRD- status (HR 1.63, 95% CI 1.07-2.48, p=0.02) were significant factors impacting PFS. Multivariate analysis for OS revealed that age (HR 1.07, 95% CI 1.03-1.10, p<0.001) and R0 resection at TRS (HR 0.19, 95% CI 0.08-0.44, p<0.001) were significant factors impacting OS. Conclusions: Germline BRCA-mutant, somatic BRCA/HRD+ HGOC was associated with improved PFS and OS regardless of primary TRS or NACT. BRCA-/HRD- was a negative prognostic factor for survival in HGOC.
e24034 Background: Active Living After Cancer (ALAC) is a 12-week evidence-based program funded by the Cancer Prevention and Research Institute of Texas (CPRIT) to provide physical activity and survivorship education to cancer survivors. Given the limited data evaluating the effects of physical activity educational programs in gynecologic cancer survivors, we aim to assess the effects of the ALAC intervention in this patient population. Methods: A retrospective analysis was performed on gynecologic cancer survivors who participated in ALAC from 2017 to 2021. The 12-week ALAC program included weekly meetings (in-person or virtual) led by a facilitator providing physical activity behavioral skills training, leading 10 minutes of exercise, and discussing topics related to cancer survivorship. Surveys and functional testing assessments were collected pre- and post-program which included: The Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) and 30-second sit-to-stand. A patient-reported outcomes survey was used to assess patient perceived benefits and program satisfaction. Results: Thirty-two patients participated in ALAC and 22 completed pre- and post-program assessments. The mean age of participants was 60.2 years (range 50.7-69.7 years) and mean number of classes attended was 8 (range 0-12 classes). Prior cancer diagnoses included 14 cervical, 11 uterine, and 7 ovarian cancers. A significant improvement was seen pre- and post-ALAC in moderate-intensity physical activity minutes (n = 17, 97 vs 252 minutes, p = 0.007) by GSLTPAQ and 30-second sit-to-stand test (n = 16, 12.3 vs 15.8 repetitions, p = 0.003) in our cohort. The post-ALAC patient reported outcome survey (n = 22) revealed improvement in emotional well-being (90%), physical well-being (91%), physical activity level (100%), comfort speaking openly in a group (85%), and willingness to discuss their cancer journey (66%). Overall, 95.3% of participants were satisfied with the ALAC program and 100% of participants would recommend the ALAC program to other cancer survivors. Conclusions: Educational physical activity-based programs like ALAC improve physical functioning and moderate-intensity physical activity in gynecologic cancer survivors. Further studies on the long-term health benefits of structured educational programs which promote active lifestyles in gynecologic cancer survivors are needed in larger patient cohorts.
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