Background Androgen deprivation therapy (ADT) has been associated with adverse effects on the brain. ADT alters testosterone levels via its action on the hypothalamus‐pituitary‐gonadal axis and may influence hypothalamic functions. Given the wide regional connectivity of the hypothalamus and its role in regulating cognition and behavior, we assessed the effects of ADT on hypothalamic resting state functional connectivity (rsFC) and their cognitive and clinical correlates. Methods In a prospective observational study, 22 men with nonmetastatic prostate cancer receiving ADT and 28 patients not receiving ADT (controls), matched in age, years of education, and Montreal Cognitive Assessment score, participated in N‐back task and quality of life (QoL) assessments and brain imaging at baseline and at 6 months. Imaging data were processed with published routines and the results of a group by time flexible factorial analysis were evaluated at a corrected threshold. Results ADT and control groups did not differ in N‐back performance or QoL across time points. Relative to controls, patients receiving ADT showed significantly higher hypothalamus‐right mid‐cingulate cortex (MCC) and precentral gyrus (PCG) rsFC during follow‐up versus baseline. Further, the changes in MCC and PCG rsFC were correlated positively with the change in QoL score and 0‐back correct response rate, respectively, in patients with undergoing ADT. Conclusion Six‐month ADT affects hypothalamic functional connectivity with brain regions critical to cognitive motor and affective functions. Elevated hypothalamic MCC and PCG connectivity likely serve to functionally compensate for the effects of ADT and sustain attention and overall QoL. The longer‐term effects of ADT remain to be investigated.

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Androgen deprivation therapy (ADT) has been associated with adverse effects on cognition. However, we currently lack understanding of the neurobiology and prognostic markers of these effects. Given that ADT acts via the hypothalamus–pituitary–gonadal axis, we assessed whether baseline hypothalamic resting state functional connectivity (rsFC) could predict changes in working memory and quality of life in prostate cancer patients following androgen deprivation. In a prospective observational study, 28 men with non-metastatic prostate cancer receiving ADT and 38 patients not receiving ADT (controls), matched in age, years of education and Montreal Cognitive Assessment score, participated in brain imaging at baseline, and N-back task and quality-of-life (QoL) assessments at baseline and at 6 months follow-up. Imaging data were processed with published routines and evaluated at a corrected threshold. ADT and control groups did not differ in N-back performance or QoL across time points. In ADT, the changes in 0-back correct response rate (follow-up—baseline) were correlated with baseline hypothalamus-precentral gyrus rsFC; the changes in 1-back correct response rate and reaction time were each correlated with hypothalamus-middle frontal gyrus and superior parietal lobule rsFC. The changes in physical well-being subscore of QoL were correlated with baseline hypothalamus-anterior cingulate and cuneus rsFC. The hypothalamus rsFCs predicted N-back and QoL change with an area under the receiver operating characteristic curve of 0.93 and 0.73, respectively. Baseline hypothalamus-frontoparietal and salience network rsFC’s predict inter-subject variations in the changes in working-memory and QoL following 6 months of ADT. Whether and how hypothalamic rsFCs may predict the cognitive and QoL effects with longer-term ADT remain to be investigated.

79 Background: Patient-trial matching is a critical step in clinical research recruitment that requires extensive review of clinical data and trial requirements. Prescreening, defined as identifying potentially eligible patients using select eligibility criteria, may streamline the process and increase study enrollment. We describe the real-world experience of implementing a standardized, universal clinical research prescreening protocol within a VA cancer center and its impact on research enrollment. Methods: An IRB approved prescreening protocol was implemented at the VACT Cancer Center in March 2017. All patients with a suspected or confirmed diagnosis of cancer are identified through tumor boards, oncology consults, and clinic lists. Research coordinators perform chart review and manually enter patient demographics, cancer type and stage, and treatment history into a REDCap (Research Electronic Data Capture) database. All clinical trials and their eligibility criteria are also entered into REDCap and updated regularly. REDCap generates real time lists of potential research studies for each patient based on his/her recorded data. The primary oncologist is alerted to a patient’s potential eligibility prior to upcoming clinic visits and thus can plan to discuss clinical research enrollment as appropriate. Results: From March 2017 to December 2020, a total of 2548 unique patients were prescreened into REDCAP. The mean age was 71.5 years, 97.5% were male, and 15.5% were African American. 32.57 % patients had genitourinary cancer, 17.15% had lung cancer, and 46.15% were undergoing malignancy workup. 1412 patients were potentially eligible after prescreening and 556 patients were ultimately enrolled in studies. The number of patients enrolled on therapeutic clinical trials increased after the implementation of the prescreening protocol (35 in 2017, 64 in 2018, 78 in 2019, and 55 in 2020 despite the COVID19 pandemic). Biorepository study enrollment increased from 8 in 2019 to 15 in 2020. The prescreening protocol also enabled 200 patients to be enrolled onto a lung nodule liquid biopsy study from 2017 to 2019. Our prescreening process captured 98.57% of lung cancer patients entered into the cancer registry during the same time period. Conclusions: Universal prescreening streamlined research recruitment operations and was associated with yearly increases in clinical research enrollment at a VA cancer center. Our protocol identified most new lung cancer patients, suggesting that, at least for this malignancy, potential study patients were not missed. The protocol was integral in our program becoming the top accruing VA site for NCI’s National Clinical Trial Network (NCTN) studies since 2019.