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Prostate cancer (PC) rarely metastasizes to the central nervous system (CNS). In this retrospective single-institution study at a tertiary cancer center, we aimed to evaluate the clinical and genetic characteristics of advanced PC patients with CNS metastases.Between January 2010 and March 2020, 12 out of 579 patients with extracranial metastatic PC were identified to have CNS metastases based on imaging, including six patients with brain metastases (BMs), five patients with dural metastases, and one unknown. These patients were followed up through March 2022. Clinical data were compared to the overall cohort of patients evaluated at our cancer center during that decade. Genetics information was also analyzed for the patients with available data via cell-free DNA (cfDNA) blood samples.Median time from development of extracranial metastatic disease to development of CNS metastases was 5.5 years (95% CI, 1.8-7.0). Median overall survival (mOS) from diagnosis of CNS metastases was 6.1 months (95% CI, 5.8-8.2). Notably, there was no significant difference in mOS after development of extracranial metastases in patients with CNS metastases (6.4 years; 95% CI, 4.6-7.9) compared to the patients without known CNS metastases (5.2 years; 95% CI, 4.6-5.7) (P = .91). For the cohort with CNS metastases, nine patients had germline testing and seven patients had somatic testing via cfDNA.PC patients with CNS metastases did not often die from a neurological cause. With advancing therapies, the overall prognosis of metastatic PC continues to improve, and CNS metastases will become more common.

Immune checkpoint inhibitors are a well-established treatment option for advanced urothelial carcinoma, and biomarkers of response are needed for better patient selection. We show that metastatic disease confined to lymph nodes is associated with better outcomes, while metastases to liver, bone or both are associated with poor outcomes with immune checkpoint inhibitor therapy. Results are hypothesis-generating but relevant to practice. BACKGROUND: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. METHODS: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd(+) line. RESULTS: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd(+) line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd(+) line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. CONCLUSION: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

Prostate cancer is one of the most common malignancies in men. Over time, it can metastasize and become lethal once it exhausts hormonal therapies and transitions into castration-resistant prostate cancer (CRPC). Several therapies have been recently approved for advanced prostate cancer, but identifying biomarkers for current treatments and searching for more effective treatments are urgently needed. Liquid biopsy is a powerful tool for isolating genetic material, proteins, and whole tumor cells from the blood. In recent decades, this technology has rapidly advanced, allowing for better insights into the pathogenesis and treatment response in different stages of prostate cancer. In this review, we summarize important clinical studies involving liquid biopsies in prostate cancer with a focus on advanced disease, notably regarding circulating tumor DNA, circulating tumor cells, and exosomes. We highlight the progress and the challenges that still exist for these technologies. Finally, we discuss promising avenues that will further expand the importance of liquid biopsy in the care for prostate cancer patients.

An 84-year-old man with nonmetastatic castrate-sensitive prostate cancer was referred for a 68Ga-prostate-specific membrane antigen (PSMA) PET/CT scan with a prostate-specific antigen level of 3.6 ng/mL for restaging. He was 22 years post-radical prostatectomy and had salvage radiation being managed with intermittent hormonal therapy. Imaging revealed a right lower lobe mass with increased PSMA uptake (SUVmax 6.2). Biopsy and subsequent immunostaining determined the mass to be diffuse large B-cell lymphoma. We report a case of diffuse large B-cell lymphoma diagnosed in the setting of PSMA positivity, highlighting awareness for oncologists and radiologists to know this possibility.

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have increasingly become the standard of care for various advanced malignancies, including metastatic clear cell renal cell carcinoma (mccRCC). Most ICIs currently used in clinical practice inhibit the interaction between the programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) complex. A deeper understanding of this interaction and PD-L1 expression in tumors has led to more effective therapies in the treatment of advanced cancers, but the debate regarding the utility of PD-L1 as a biomarker continues. OBJECTIVE: We aimed to systematically evaluate the role of PD-L1 in mccRCC in terms of expression and treatment implications. METHODS: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through August 31, 2020. Titles and abstracts were screened to identify articles for full-text review. A hand search was also performed using Google Scholar and the bibliography to relevant studies. RESULTS: A total of 26 articles were identified, and relevant data were extracted and organized. The available information regarding PD-L1 expression in mccRCC from both prospective clinical trials and retrospective studies were summarized. We discussed the utility of PD-L1 as a predictive and prognostic biomarker in mccRCC, its association with other potential biomarkers, and the pattern and level of expression of PD-L1 in primary versus metastatic tumors. CONCLUSIONS: Although significant progress has been made, much more remains to be learned regarding the differences between PD-L1+ and PD-L1- ccRCC tumors, in terms of both the underlying biology and clinical responses to immunotherapy and other agents.

BACKGROUND: Vaso-occlusive pain leads to high acute care utilization among patients with sickle cell disease (SCD). Data suggest that clinical pathways (CPWs) reduce variation in the management of vaso-occlusive pain and improve clinical outcomes. METHODS: We implemented and evaluated a CPW for vaso-occlusive pain at our institution using a before and after study design. The primary objective was to decrease acute care utilization among patients with SCD, which was assessed by the primary outcome measures of hospital length of stay (LOS), 30-day readmission rate, and total hospitalizations annually per patient. Secondary outcome measures were packed red blood cell transfusions, and acute chest syndrome incidence. Patient-controlled analgesia use and promethazine use were assessed to estimate CPW utilization. RESULTS: 344 admissions in 112 patients were analyzed, of which 193 admissions occurred pre-CPW and 151 admissions occurred post-CPW implementation. Post-CPW implementation, we observed a significant decrease in hospital admissions annually per patient, an increase in patient-controlled analgesia (PCA) use, and a decrease in intravenous (IV) promethazine use. We observed trends toward decreased 30-day readmission rate and increased ACS incidence, which were not statistically significant. No effect was found on hospital LOS. CONCLUSION: CPW implementation at our institution reduced variation in management and decreased hospital admissions for vaso-occlusive pain.

Autoimmune myelofibrosis (AIMF) is a rare complication of systemic lupus erythematosus (SLE) characterized by deposition of collagen and reticulin fibers in the bone marrow mediated by an aberrant production of fibrogenic cytokines and autoantibodies. Cytopenias in SLE/AIMF result from simultaneous underproduction secondary to myelofibrosis and peripheral destruction of blood cells. A 43-year-old woman was admitted for symptomatic pancytopenia associated with chest pain, dizziness, and headaches. Initial studies showed pancytopenia with diffuse osteolytic lesions particularly prominent on the skull, suggesting a possible malignancy. Additional diagnostic workup revealed a new diagnosis of SLE (+ANA, +dsDNA, low C3/C4), myelofibrosis secondary to SLE (JAK2 and CALR negative; bone marrow biopsy showing diffuse grade 4 reticulin and collagen fibrosis), and concurrent immune thrombocytopenic purpura (ITP). She experienced severe thrombocytopenia with minimal response to frequent platelet transfusions and multiple first-line therapies including high-dose prednisone, hydroxychloroquine, and intravenous immunoglobulin. Ultimately, she was treated with rituximab and romiplostim that resulted in stabilization of her platelet count and resolution of osteolytic lesions at 1-year follow-up. The concomitant occurrence of AIMF and ITP in SLE is particularly rare and carries considerable prognostic significance. This presentation of SLE was further complicated by osteolytic lesions in the absence of malignancy, resistance to first-line therapies, and high mortality risk with severe unremitting thrombocytopenia dependent on platelet transfusions. As this constellation of symptoms and pathology posed significant challenges in diagnosis and management, representing the first documented case, we review the literature and discuss our approach and successful treatment.

BACKGROUND: Black individuals and veterans are at higher risk for developing lung cancer compared with that of the general population. Evidence suggests the screening criteria have been too conservative for this population. METHODS: This study is a retrospective chart review examining the applicability of the 2013 United States Preventive Services Task Force lung cancer screening guidelines in a US Department of Veteran Affairs institution that served a a predominantly black population. Patients diagnosed with stage 1 or 2 lung cancer from 2005 through 2017 were included and grouped by whether or not they met United States Preventive Services Task Force screening criteria. RESULTS: There was a significantly higher proportion of Black patients in the study group that did not meet screening criteria (68% vs 54%, P = .04), highlighting the concern that this population was being underscreened with the 2013 guidelines. CONCLUSIONS: An individualized, risk-based screening model could be more effective at diagnosing early-stage lung cancer and requires more investigation.

Alcohol misuse is a risk factor for many adverse health outcomes. Alcohol misuse has been associated with an imbalance of gut microbiota in preclinical models and alcoholic diseases. We hypothesized that daily alcohol use would change the community composition and structure of the human colonic gut microbiota. Thirty-four polyp-free individuals donated 97 snap-frozen colonic biopsies. Microbial DNA was sequenced for the 16S ribosomal RNA gene hypervariable region 4. The SILVA database was used for operational taxonomic unit classification. Alcohol use was assessed using a food frequency questionnaire. We compared the biodiversity and relative abundance of the taxa among never drinkers (ND, n = 9), former drinkers (FD, n = 10), current light drinkers (LD,2 drinks daily, n = 9), and current heavy drinkers (HD, ≥2 drinks daily, n = 6). False discovery rate-adjusted P values (q values) .05 indicated statistical significance. HD had the lowest α diversity (Shannon index q value0.001), and HD's microbial composition differed the most from the other groups (P value = .002). LD had the highest relative abundance of Akkermansia (q values0.001). HD had the lowest relative abundance of Subdoligranulum, Roseburia, and Lachnospiraceaeunc91005 but the highest relative abundance of Lachnospiraceaeunc8895 (all q values0.05). The multivariable negative binomial regression model supported these observations. ND and FD had a similar microbial profile. Heavy alcohol use was associated with impaired gut microbiota that may partially mediate its effect on health outcomes.

Colorectal cancer screening is essential to detect and remove premalignant lesions to prevent the development of colorectal cancer. Multiple screening modalities are available, including colonoscopy and stool-based testing. Colonoscopy remains the gold standard for detection and removal of premalignant colorectal lesions. Screening guidelines by the American Cancer Society now recommend initiating screening for all average-risk adults at 45 years old. Family history of colorectal cancer, other cancers, and advanced colon polyps are strong risk factors that must be considered in order to implement earlier testing. Epidemiologic studies continue to show disparities in colorectal cancer incidence and mortality and wide variability in screening rates.

OBJECTIVE Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity, and diabetes. We examined the association between hypertension, obesity, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak. RESEARCH DESIGN AND METHODS Data were collected from 287 consecutive patients with COVID-19 hospitalized at two hospitals in New Orleans, LA, from 30 March to 5 April 2020. MetS was identified per World Health Organization criteria. RESULTS Among 287 patients (mean age 61.5 years; female, 56.8%; non-Hispanic Black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR] 3.42 [95% CI 1.52–7.69]), intensive care unit requirement (ICU) (aOR 4.59 [CI 2.53–8.32]), invasive mechanical ventilation (IMV) (aOR 4.71 [95% CI 2.50–8.87]), and acute respiratory distress syndrome (ARDS) (aOR 4.70 [95% CI 2.25–9.82]) compared with non-MetS. Multivariable analyses of hypertension, obesity, and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR 2.18 [95% CI 1.25–3.81]), ARDS (aOR 2.44 [95% CI 1.28–4.65]), and IMV (aOR 2.36 [95% CI 1.33–4.21]). Diabetes was associated with ICU (aOR 2.22 [95% CI 1.24–3.98]) and IMV (aOR 2.12 [95% CI 1.16–3.89]). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, CRP and lactate dehydrogenase (LDH), were associated with mortality (CRP [aOR 3.66] [95% CI 1.22–10.97] and LDH [aOR 3.49] [95% CI 1.78–6.83]). CONCLUSIONS In predominantly Black patients hospitalized for COVID-19, the clustering of hypertension, obesity, and diabetes as MetS increased the odds of mortality compared with these comorbidities individually.

About one-third of advanced renal cell carcinoma (RCC) patients have bone metastases, which subsequently leads to the development of skeletal-related events (SREs), broadly defined to include surgery and radiation to bone, bone pain, pathological fracture, spinal cord compression, or hypercalcemia. The cumulative impact of SREs in RCC has not been well studied. SREs increase morbidity and mortality of RCC patients, although many interventions do significantly reduce their rates of development and improve prognosis. We performed a systematic review from the existing literature in PubMed from January 2002 through September 2019 and summarized the body of evidence regarding the development, prevention, prognosis and treatment of SREs in advanced RCC patients.

248 Background: mCRPC patients with liver metastases have a poor prognosis and often progress rapidly on a variety of treatments. Previously, preliminary ctDNA analyses of mCRPC patients with liver metastases showed a range of commonly altered genes in patients with liver metastases (Ranasinghe et al; 2019). In this follow-up, we evaluated ctDNA alterations in an expanded cohort of mCRPC patients with liver metastases. Methods: From Tulane Cancer Center, retrospective review of mCRPC patients was used to identify patients with confirmed liver metastasis. All liver metastases were confirmed based on imaging data. All patients included had ctDNA evaluated with a multi-gene cancer panel via Guardant 360 assay (Guardant Health, Inc). Additional clinical annotation including family history, germline testing, staging, imaging, and laboratory values. Statistical analyses were performed with Fisher’s Exact and Wilcoxon Rank Sum tests. Results: 158 mCRPC patients with appropriate diagnostic imaging as well as ctDNA testing. From this group, 8% (n= 12) had confirmed liver metastases. Among the patients with liver metastasis, the most common alterations detected were in AR (50%; 6/12) and PIK3CA (25%; 3/12). Patients with liver metastasis were more likely to have amplifications in FGFR1 detected in their ctDNA (OR= 14.40; 95% C.I. (1.83, 113.22); p= 0.03). In addition to ctDNA, germline data was assessed, and it was found that patients with liver metastasis were more likely to have a pathogenic germline mutation (OR= 7.61; 95% C.I. (2.85, 20.31); p

67 Background: Radium-223 (Ra-223), a targeted alpha-emitting radiopharmaceutical approved for the treatment of metastatic prostate cancer (mPC), can cause myelosuppression. In the ALSYMPCA trial 30% of patients developed cytopenias, including 13% with grade 3/4 anemia. Therefore, it is recommended that only men with a hemoglobin ≥10 g/dL, platelet count ≥100,000/mm3, and ANC ≥1,500/mm3 be considered for Ra-223. Since the FDA approval of Ra-223 in 2013, several new treatments have been approved for men with mPC. With the changing therapeutic landscape, we anticipate more patients (pts) will have preexisting cytopenia prior to Ra-223 consideration. Hence, clinicians are increasingly likely to face the dilemma of whether it is safe and efficacious to administer Ra-223 in the setting of Hgb ≤10 with/without RBC transfusion support. Methods: We retrospectively identified pts with mPC treated with Ra-223, including a subset of men with Hgb 10g/dL, men with Hgb

230 Background: Somatic alterations change over time in response to treatment and disease progression in patients with prostate cancer (PCa). We report ctDNA findings of patients who died from PCa within 3 months of a ctDNA assessment to better characterize patients with fatal disease. Methods: A total of 118 patients with PCa specific mortality who had been treated at Tulane Cancer Center and had ctDNA assessments between 2015 and 2022. The ctDNA was assessed by Guardant360 (Guardent Health, Inc) assays to identify alterations, pathogenic mutations and/or copy number alterations (CNAs) in cancer-related genes. Clinical annotation including treatment history, genetics, and staging were also obtained. Statistical analyses included Fischer’s Exact and Wilcoxon tests. Results: Of the 118 patients with PCa specific mortality, 42% (49/118) had a ctDNA assessment

243 Background: Lutetium-177- PSMA-617 (Lu-177) is a radioligand therapy that delivers radiation to PSMA-expressing cells in patients with advanced prostate cancer. In this study, we aimed to analyze ctDNA in responders and non-responders after Lu-177 treatments. Methods: Data was retrospectively collected on 31 heavily pre-treated metastatic CRPC patients who received Lu-177 treatment at Tulane Cancer Center. All patients fulfilled VISION criteria for treatment and all had ctDNA assessment with Guardant 360 within 30 days prior to first treatment with Lu-177. Of the 31 patients, 7 had paired ctDNA assessment both prior initiation of treatment and at the end of treatment. Clinical data such as PSA response (PSA decline 50% or more) to Lu-177, initial diagnosis, pathology, treatment history, and relevant germline genetic data were collected. Results: Of the 31 patients who received Lu-177 treatment, 18 had PSA response to Lu-177 (responders) and 13 did not (non-responders). In ctDNA mutational analyses, there were no significant differences detected prior to treatment between responders and non-responders. There was, however, a significant increase in the presence of copy number amplifications in non-responders (n= 11/13) when compared to responders (n= 7/18) (OR= 8.64, 95% C.I. [1.46, 51.25)], p = 0.0250). Amplification was detected in 10 genes in non-responders, whereas responders only had amplifications in AR (7/18) and EGFR (1/18). The most frequently amplified genes in non-responders were AR (8/13), CCNE1 (6/13), EGFR (4/13), and FGFR1 (4/13). Furthermore, in analysis of the 7 patients with paired ctDNA assessments, amplifications increased during treatment with Lu-177. Conclusions: Radioligand therapy with Lu-177 has been shown to prolong life and reduce disease progression. Our analysis of the cohort of Lu-177 treated patients showed that the presence of gene amplifications in ctDNA may play a role in predicting resistance to treatment with Lu-177.

35 Background: Genetic differences between African American and Caucasian patients with advanced prostate cancer may contribute to racial disparities in terms of treatment outcomes and survival, hence further exploration is warranted. We assessed ctDNA differences between African American and Caucasian men in the setting of CRPC post treatment with abiraterone and/or enzalutamide. Methods: From 2015 through 2022 at Tulane Cancer Center, 250 patients with CRPC including 50 African Americans and 200 Caucasian with prior abiraterone and/or enzalutamide treatment were included. All patients had ctDNA assessed via Guardant360. Data including both gene mutations and types of mutations were for between 73-80 genes. Clinical annotation including initial staging, treatment history, and genetic testing were obtained. Statistical analyses included Fisher’s exact test and Wilcoxon rank-sum test. Results: The most common pathogenic/likely pathogenic (P/LP) alterations in both African Americans and Caucasians were TP53 (44% and 46%, respectively), AR (50% and 39%), and PIK3CA (14% and 9%). CDK12 (OR= 8.955, 95% C.I. [2.156, 37.192], p=0.003) and KIT (OR= 5.710, 95% C.I. [1.235, 26.397]. p=0.031) alterations were more frequently detected in African Americans. In terms of pathologic mutation type, frameshift mutations were significantly more frequent in African Americans (OR= 2.293, 95% C.I. [1.103, 4.769], p=0.035). All patients were CRPC at the time of testing and had prior abiraterone and/or enzalutamide, but there were no significant differences between African American and Caucasian patients with regards to prior life-extending therapies. Conclusions: African Americans with CRPC post treatment with abiraterone and/or enzalutamide had a higher frequency of P/LP CDK12 and KIT mutations, which have both been shown to lead to aggressive clinical features and treatment resistance. African Americans also had a higher incidence of frameshift mutations, a finding not previously noted. [Table: see text]

253 Background: Approximately 3-5% of advanced prostate cancer patients have pathogenic BRCA2 mutations in germline tests. In this study, we examine the relationship between pathogenic germline BRCA2 mutation and somatic changes in ctDNA. Methods: Germline screenings were performed by Invitae multi-cancer gene panel which includes 50-84 genes. ctDNA alterations were detected by Guardant 360 assays which report somatic changes in 70-83 genes. All ctDNA samples were collected in post-abiraterone and/or enzalutamide (in CRPC patients). Any pathogenic/likely pathogenic somatic alterations in the ctDNAs with more than 0.1% of allelic fraction were included in this cohort. The type of mutation detected in ctDNA was also assessed (truncating, point, etc.). Statistical significance for comparison is calculated with Fischer Exact Probablity Test and Chi-Square Test. Results: A total of 11 patients had germline BRCA2 pathogenic mutations and ctDNA assays; 267 patients had no germline DNA pathogenic alterations and ctDNA assays. Compared to germline normal patients, the germline BRCA2 mutations were less likely to have AR alterations on ctDNA (OR=0.2133, 95% C.I. [0.087, 0.525], p-value = 0.0003). BRCA2 germline positive patients were also more likely to have a mutated BRCA1, BRCA2, and TP53 ctDNA (OR=7.899, 95% C.I. [1.2745, 48.9548], p=0.055), (OR=7.899, 95% C.I. [1.7529, 16.059], p=0.008), and (OR=6.442, 95% C.I. [2.449, 16.946], p=0.00001), respectively. All other ctDNA assessed genes were mutated at a similar frequency between germline BRCA2 mutated and “normal” germline patients. BRCA2 germline mutations patients are less likely to have copy number alterations (CNVs) (OR=0.3992, 95% C.I. [0.2168, 0.7352], p=0.0031) and more likely to have frameshift mutations (OR=2.3182, 95% C.I. [1.169, 4.5972], p=0.0183). Conclusions: The ctDNA testing in this CRPC population (after abiraterone and/or enzalutamide) was less likely to find AR alterations and more likely to find pathogenic mutations for BRCA1, BRCA2, and TP53 in BRCA2 germline positive patients. In addition, BRCA2 germline positive CRPC patients were more likely to have frameshift mutations and less likely to have CNVs than those with an intact germline. Characterizing the mutational landscape in BRCA2 germline mutated patients may help to better define underlying disease biology. Those with BRCA mutated germline may be less likely to have AR driven tumors. More study is needed to better understand patients with underlying DNA repair defects.

721 Background: Current methodologies for monitoring treatment response are largely based on conventional scans and/or tumor biopsies, which may be limited in their ability to accurately assess disease burden at the molecular level. Circulating tumor DNA (ctDNA) detection in blood has emerged as a prognostic and predictive biomarker and has shown to better assess treatment response in patients receiving immune checkpoint inhibitors (ICI). We conducted a prospective, pilot study to investigate the concordance of serial ctDNA detection and dynamics with radiographic response in patients with advanced GU malignancies undergoing ICI-based treatment. Methods: Twenty patients with histologically confirmed advanced GU malignancies (renal, urothelial, and prostate) were enrolled in the prospective study. All eligible patients received ICI treatment for at least 12 weeks and were followed by serial collection of blood samples every 6-8 weeks until disease progression. Conventional scans were performed approximately every 12 weeks until disease progression. Overall response rate (ORR) by investigator was reported and associated with ctDNA detection. Results: ctDNA analysis was performed on 122 plasma samples obtained from 20 patients (N=15 renal cell carcinoma; N=4 urothelial carcinoma; N=1 prostate cancer). Prior therapies to ICI-based treatment included chemotherapy (10%), hormonal therapy (5%) and anti-VEGF (5%). After study enrollment, patients received anti-PD-1 (95%), anti-CTLA-4 (30%) or anti-PD-L1 (5%) with an ORR of 70% as best response. With a median follow-up of 19 months (range: 4-48), progressive disease was observed in 7 patients. Nineteen patients had longitudinal plasma samples available and ctDNA detection at any time point was 45% (9/20). The overall concordance between ctDNA dynamics and radiographic response at 12 weeks was observed in 89% (17/19) of patients. Of these 17 concordant patients, one patient showed transient ctDNA positivity followed by clearance at the last two timepoints on treatment. The two patients with discordant results included the ones with CNS-only metastasis (ctDNA negative). Of the 7 patients who progressed on ICI, ctDNA was detected in five (71%); the remaining two had CNS-only metastases. The last patient had a single time point available on treatment that showed ctDNA-positivity and passed away 7 weeks after molecular evidence of disease. Conclusions: In this study, serial collection of blood samples for ctDNA analysis to monitor response to ICI-based therapiesin patients with advanced GU tumors was feasible. There was a high concordance rate between radiological imaging and ctDNA data, especially in extra-CNS disease. Further studies are needed to validate ctDNA as a tool to aid disease monitoring in patients treated with ICI.

Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials.UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were abstracted from chart reviews by investigators at each site. The observed response rate (ORR) was investigator-assessed for patients with at least 1 post-baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy.The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression-free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06).In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate30 mL/min and significant comorbidities.Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer. This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations. Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real-world setting, and support the use of this drug in broader patient populations.

Simple Summary Genitourinary malignancies include cancers along the urinary tract and the male reproductive tract, encompassing the adrenal glands, kidneys, bladder, prostate, and testicles. Immunotherapy, which treats cancer by using the immune system to attack malignant cells, has historically been successful in treating some types of genitourinary cancers, especially of the bladder and kidney. In the past decade, a more precise method of immunotherapy, known as immune checkpoint inhibition, has gained popularity as it enhances the immune system’s ability to recognize and destroy tumor cells. Several immune checkpoint inhibitors have achieved success in patients with advanced genitourinary cancers. This review provides a brief overview of traditional immunotherapies, focuses on how immune checkpoint inhibitors have achieved success in patients with advanced cancers, and investigates the role for immunotherapy in genitourinary malignancies in the future. Abstract For decades, limited options existed to treat metastatic genitourinary cancers, including treatment options that could be classified as immunotherapy. Historically, immunotherapy centered on systemic cytokines for the treatment of metastatic kidney cancer, which had several adverse effects, as well as the Bacillus Calmette–Guérin vaccine for non-metastatic bladder cancer. Within the past decade, advances in immunotherapy have led to several approvals from the United States Food and Drug Administration, particularly in the field of immune checkpoint inhibition. Immune checkpoint inhibitors (ICIs) are now being used extensively to treat multiple solid tumors, including kidney and bladder cancers, and they are also being tested in many other cancers. Despite encouraging data from phase 2/3 clinical trials, less is known about biomarkers that may predict better response to ICIs. The effect of ICIs in genitourinary cancers is heterogeneous, with some tumor types having little clinical data available, or ICIs having limited activity in other tumors. In this review, we briefly discuss approved immunotherapy agents prior to the time of ICIs. Then, given the emergence of this class of agents, we summarize the several important ICIs and the clinical trials that led to their approval. Finally, we mention ongoing and future clinical trials.

Background The outcomes of metastatic hormone-sensitive prostate cancer (mHSPC) have significantly improved through treatment intensification, yet Black representation in those studies is suboptimal. Methods A multi-institutional, retrospective analysis of Black men with mHSPC was conducted, focusing on baseline demographics, treatment patterns, genomic profiles, clinical outcomes including prostate-specific antigen response, time to castrate-resistant prostate cancer (CRPC), and subsequent treatments. Results A total of 107 patients, median age 64 years, 62% with de novo metastases at diagnosis and 64% with high-volume disease, were included. Twenty-nine patients (27%) were treated with androgen deprivation therapy (ADT) with and without first generation anti-androgens, while 20%, 38% and 5% received chemotherapy, abiraterone, and enzalutamide, respectively. At time of data cut-off, 57 (54%) patients had developed CRPC, with a median time to CRPC of 25.4 months (95% CI 20.3-30.4). The median time to CRPC was 46.3 months (18.9-73.7) and 23.4 months (18.6-28.2) for patients who received ADT with or without first-generation anti-androgens and treatment intensification, respectively. The 2-year survival rate was 93.3%, and estimated median overall survival of was 74.9 months (95% CI, 68.7-81.0). Most patients (90%) underwent germline testing; the most frequent known alterations were found within the DNA repair group of genes. Somatic testing revealed pathogenic alterations of interest, notably TP53 (24%) and CDK12 (12%). Conclusion In our cohort, Black men with mHSPC presented with a high proportion of de novo metastases and high-volume disease. Treatment outcomes were very favorable with ADT-based regimens. The genomic landscape suggests different molecular profile relative to White patients with potential therapeutic implications.

e18624 Background: Four in 10 people aged 60-69 have hearing loss in frequencies that mediate speech comprehension. Untreated losses undermine medication adherence, increase risk for accidental injury, and generate higher total healthcare expenditures. Genitourinary (GU) malignancies are most frequently diagnosed in people over 60, and these patients are commonly exposed to ototoxic treatments like platinum-based chemotherapy. We hypothesized that a significant number of GU patients would fail hearing screenings at levels reflecting clinically significant hearing loss. Methods: This is a prospective, two-cohort pilot study conducted at Tulane Medical Center. Consecutive patients with active GU malignancies who did not use hearing aids were enrolled in cohort A. The primary objective of cohort A (screening) was to determine the prevalence of hearing loss among GU patients. Cohort B (interventional) will investigate the efficacy of a non-custom amplifier in improving communication for patients with hearing loss. The hearing screening consisted of a 9-item Self-Assessment of Communication (SAC) and a 25 decibel (dB) pure tone hearing screening at 1 kHz, 2 kHz, 4 kHz via an Earscan3 portable audiometer with headphones in a quiet exam room. The primary endpoint was the proportion of patients who failed the hearing screening (missed ≥ 2/6 tones). The SAC generates a global handicap score (none, slight, mild-to-moderate, severe). Surveys identifying any amount of handicap were considered positive. Patients who failed screenings were offered referrals to audiology. Here, we present results from cohort A. Results: From 8/21 to 1/22, 66 patients were invited to participate. Nine patients screen-failed (n = 8 hearing aids; n = 1 uninterested). Cohort A enrolled 57 patients [median age 68 (33-86); 91% men; 60% prostate, 24% kidney and 14% bladder cancer]. Most patients (82%) had evidence of metastatic disease and 12%, 19%, 36%, 21% of patients were receiving chemotherapy, immunotherapy, hormonal therapy, and no active therapy, respectively. Twenty (35%) patients had prior exposure to neurotoxic chemotherapy. Forty patients (70%) met the primary endpoint. Compared to the pure tone screening, the SAC had a specificity of 94%, and a sensitivity of 40%. The SAC asks patients for a situation where they want to hear better; 61% of patients who volunteered a scenario (17/28) identified a complex listening environment like an outpatient encounter. A minority of patients (n = 3) accepted audiology referrals after failing screenings. Cohort B is actively enrolling. Conclusions: Clinically significant hearing loss was prevalent among patients with GU malignancies. Patients reported struggling in listening situations with auditory demands like outpatient encounters but were unable to self-identify losses and did not pursue audiology referrals after failed screenings. Interventional studies addressing this unmet need are warranted.

5013 Background: Black men have been underrepresented in large-scale molecular prostate cancer (PC) surveys, despite having higher PC incidence and mortality. Since molecular profiling to guide the use of targeted agents is increasingly important in mCRPC, we compared precision medicine data and utilization in a cohort of black and white men with mCRPC. Methods: The PROMISE precision medicine database is an academic collaboration to compile clinical and genomic data from men with PC. All patients have had germline and/or somatic genetic testing performed. Eligibility criteria for this analysis included a diagnosis of mCRPC with available race and biomarker data. The primary outcome was the proportion of non-Hispanic black (NHB) and non-Hispanic white (NHW) men with actionable molecular data, defined as the presence of mismatch repair deficiency (MMRd/MSI-H), homologous recombination repair deficiency (HRRd), tumor mutational burden (TMB) ≥ 10 mut/MB, or AR-V7. Secondary outcomes included the proportion of NHB and NHW men with other alterations, the type and timing of genomic testing performed, and the use of targeted therapy. Results: A total of 962 mCRPC patients (21.2% NHB; 78.8% NHW) met inclusion criteria of 1619 in the overall database. Median age (NHB/NHW) was 61/63; 77.5/68.8% had Gleason 8-10; 52.5/56.7% presented with de novo metastatic disease (33.8/29.9% LN, 36.2/32.2% bone and 8.3/6.1% viscera). The median time from diagnosis to first molecular result was 56.3 mo for NHB v 58.7 mo for NHW (p = 0.45). Use of blood-based molecular testing was more common in NHB men (48.7% v 36.4%, p < 0.001). Overall, 32.8% of NHB men harbored actionable molecular data compared to 30.3% of NHW men (Table). MMRd/MSI-H was more common in NHB men (9.1 v 4.9%, p = 0.04). Other than PTEN (12.7/23.8% NHB/NHW, p = 0.0001), no significant differences were seen in the 15 most frequently mutated genes, including TP53, AR, CDK12, RB1, and PIK3CA. Tumor suppressor co-mutations (PTEN/TP53/RB1) were found in 13.1% of NHB and 18.0% NHW (p = 0.13). Delivery of targeted therapy was reported in 19.6% of NHB and 23.7% of NHW men (p = 0.25) after a median of 2 CRPC lines. Median OS from development of mCRPC was 41.5 mo (95% CI, 34.7-51.3) and 44.7 mo (95% CI, 41.1-51.5) for NHB and NHW men, respectively (p = 0.14). Conclusions: In a real-world mCRPC molecular profiling cohort, we found similar overall rates of actionable molecular alterations in NHB and NHW men, but higher rates of MMRd/MSI-H and lower frequency of PTEN alterations in NHB men. We did not find differences in delivery of targeted therapy. [Table: see text]

Model-based reconstruction methods have emerged as a powerful alternative to classical Fourier-based MRI techniques, largely because of their ability to explicitly model (and therefore, potentially overcome) moderate field inhomogeneities, streamline reconstruction from non-Cartesian sampling, and even allow for the use of custom designed non-Fourier encoding methods. Their application in such scenarios, however, often comes with a substantial increase in computational cost, owing to the fact that the corresponding forward model in such settings no longer possesses a direct Fourier Transform based implementation. This paper introduces an algorithmic framework designed to reduce the computational burden associated with model-based MRI reconstruction tasks. The key innovation is the strategic sparsification of the corresponding forward operators for these models, giving rise to approximations of the forward models (and their adjoints) that admit low computational complexity application. This enables overall a reduced computational complexity application of popular iterative first-order reconstruction methods for these reconstruction tasks. Computational results obtained on both synthetic and experimental data illustrate the viability and efficiency of the approach.

Purpose Prostate cancer is a heterogeneous disease with variable clinical outcomes. Despite numerous recent approvals of novel therapies, castration-resistant prostate cancer remains lethal. A “real-world” clinical-genomic database is urgently needed to enhance our characterization of advanced prostate cancer and further enable precision oncology. Methods The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) is a consortium whose aims are to establish a repository of de-identified clinical and genomic patient data that are linked to patient outcomes. The consortium structure includes a (1) bio-informatics committee to standardize genomic data and provide quality control, (2) biostatistics committee to independently perform statistical analyses, (3) executive committee to review and select proposals of relevant questions for the consortium to address, (4) diversity/inclusion committee to address important clinical questions pertaining to racial disparities, and (5) patient advocacy committee to understand patient perspectives to improve patients’ quality of care. Results The PROMISE consortium was formed by 16 academic institutions in early 2020 and a secure RedCap database was created. The first patient record was entered into the database in April 2020 and over 1000 records have been entered as of early 2021. Data entry is proceeding as planned with the goal to have over 2500 patient records by the end of 2021. Conclusions The PROMISE consortium provides a powerful clinical-genomic platform to interrogate and address data gaps that have arisen with increased genomic testing in the clinical management of prostate cancer. The dataset incorporates data from patient populations that are often underrepresented in clinical trials, generates new hypotheses to direct further research, and addresses important clinical questions that are otherwise difficult to investigate in prospective studies.

Primary adrenal lymphoma (PAL) and primary renal lymphoma (PRL) are rare extranodal lymphomas, predominantly of diffuse large B-cell lymphoma subtype. Primary adrenal and renal lymphomas (PARL) exhibit a high predilection for the central nervous system (CNS). Therefore, current guidelines support the use of CNS prophylaxis in PARL, particularly in cases of high-risk Central Nervous System International Prognostic Index (CNS-IPI). However, the route of administration (i.e. systemic vs. intrathecal chemotherapy) has not been clearly elucidated. With this in mind, we initiated an international collaboration and literature review to analyze 50 patient cases, 20 of which received CNS prophylaxis. Based on our analysis, we conclude that PARL may indicate a need for CNS chemo-prophylaxis in the form of systemic high-dose methotrexate (HD-MTX) over intrathecal methotrexate (IT-MTX), although IT-MTX may still have utility in certain cases.

BACKGROUND Brain metastases (BMs) from metastatic prostate cancer (mPCa) are rare so little is known about clinical, genetic, and anatomic risk factors (RFs) for developing BMs. This single-center review of mPCa patients evaluates RFs for BM development. METHODS We reviewed records of mPCa patients at Tulane from 1991 – 2020 to evaluate disease, treatment, cell free DNA, and germline mutations between men with mPCa without confirmed BMs (smPCa) and men with mPCa and confirmed BMs (mPCaBMs). RESULTS We reviewed 580 patients with mPCa, of whom 11 had BMs (1.9%). Median age of stage 4 disease was 60.9 and 67.6 for men with mPCaBMs and smPCa respectively. Most mPCaBMs patients had Gleason 8 disease (81.8%) and higher median initial PSA (32 ng/mL) compared to 52.5% and 22.5 ng/mL for patients with smPCa. The development of castrate resistant disease (p=0.30) and overall survival (p=0.53) did not differ between the two populations. There were no differences in frequency of pathogenic mutations for the 68.9% (mPCaBMs) and 72.7% (smPCa) of patients with available genetic testing. Among the 11 mPCaBMs patients, 81.8% had supratentorial and 45.5% had infratentorial involvement (36.4% both). Forty-five percent had adjacent bony metastasis. Median time from SMs to BMs was 65 months (5.28 – 163.63 months), and median survival after diagnosis of BMs was 6.23 (0.49 – 70.82) months after treatment with WBRT, SRS, or GK. CONCLUSIONS The higher incidence of BMs likely reflects Tulane’s aggressive mPCa population. Interestingly 45% of BMs occurred from direct bony extension. Although 45% had infratentorial disease reflecting posterior fossa predilection, 82% of patients with BMs had supratentorial metastases. Our data suggest that men with mPCaBMs have aggressive disease and younger age at diagnosis. Due to sample size, no clinical or genetic statistically significant RFs for BMs were identified.

Simple Summary In recent years, the development of sequencing techniques to reveal the genomic information of prostate cancer tumors has allowed for the emergence of targeted therapies. Genomic aberrations in tumor cells have become popular due to the successful development of PARP inhibitors, which are particularly active in those tumors harboring DNA repair genomic defects. This review focuses on PARP inhibitors, two of which were approved for use by the US Food and Drug Administration in 2020 in metastatic castration-resistant prostate cancer. The article highlights the development of PARP inhibitors in the preclinical setting, summarizes the impactful clinical trials in the field, and discusses the need for continued research for further success in treating men with advanced prostate cancer. Abstract Metastatic castration-resistant prostate cancer (mCRPC) is an incurable malignancy with a poor prognosis. Up to 30% of patients with mCRPC have mutations in homologous recombination repair (HRR) genes. Poly (ADP-ribose) polymerase (PARP) inhibitors take advantage of HRR deficiency to kill tumor cells based on the concept of synthetic lethality. Several PARP inhibitors (PARPis) have been successful in various malignancies with HRR gene mutations including BRCA1/2, especially in breast cancer and ovarian cancer. More recently, olaparib and rucaparib were approved for mCRPC refractory to novel hormonal therapies, and other PARPis will likely follow. This article highlights the mechanism of action of PARPis at the cellular level, the preclinical data regarding a proposed mechanism of action and the effectiveness of PARPis in cancer cell lines and animal models. The article expands on the clinical development of PARPis in mCRPC, discusses potential biomarkers that may predict successful tumor control, and summarizes present and future clinical research on PARPis in the metastatic disease landscape.

Purpose: Delusions of pregnancy are associated with functional impairment and psychological distress. Previous works have focused on characterizing their etiology and identifying contributory social and cultural factors. The purpose of this review is to give an overview of the literature on medical or surgical comorbidities associated with delusions of pregnancy.Methods: We searched Google Scholar, PubMed, and PsycInfo using the terms "pregnancy delusion," "delusional pregnancy," "pseudocyesis", and "false/pseudo/phantom/spurious pregnancy" to identify all published cases of delusional pregnancies. We included cases in which medical or surgical factors might have contributed to the delusion. We extracted the following information from selected case reports: patient age, psychiatric diagnoses, medications, medical comorbidities, somatic complaints, treatment, and outcome.Results: We found that 23 of 140 cases (16.4%) were potentially influenced by concomitant medical or surgical conditions including gallstones, abdominal tumors, hyperprolactinemia, constipation, a tubal cyst, and esophageal achalasia. Medical or surgical treatment was pursued in 15 of these 23 cases, followed by mitigation of the delusion in ten cases.Conclusions: We emphasize the importance of a thorough workup including physical and gynecological examinations in patients presenting with a delusion of pregnancy. Clinicians should recognize and overcome potential barriers to undertaking comprehensive assessments in order to prevent delays in management and treatment of underlying medical or surgical conditions.