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Enfortumab Vedotin (EV) is approved for metastatic urothelial carcinoma (mUC) progressing post-platinum and PD1/L1 inhibitor therapy. Erdafitinib is approved for post-platinum mUC with activating somatic genomic alterations (GAs) in FGFR2/3. Information on the activity of EV in mUC with FGFR2/3 alterations will facilitate optimal clinical management. In this multi-center, retrospective analysis, we assessed the overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) to EV in mUC patients with and without FGFR2/3 GAs including mutations and fusions. Multivariable cox-regression and logistic regression analyses with 2-tailed p-values were used to evaluate the association of GAs with outcomes. A majority of the evaluable 60 patients were male (44/60, 78%), exhibited ECOG performance score 0–1 (53/60, 88.3%) and had a median age of 70.5 (range 48 – 88) years when starting EV. GAs in FGFR2/3 did not influence the ORR (p=0.32), OS (p=0.79) or PFS (p = 0.32) with EV. In conclusion, FGFR2/3 GAs did not appear to compromise major outcomes with EV in mUC. Larger studies are required to further evaluate the impact of FGFR2/3 GAs on the activity of EV and the optimal sequencing of EV and erdafitinib in mUC.

Leflunomide has not been previously associated with thrombotic thrombocytopenic purpura (TTP), a rare life-threatening clinical syndrome characterized by thrombotic microangiopathy (TMA) due to inability to cleave ADAMTS13. Here, we present the first case of leflunomide-induced TTP. Our patient developed encephalopathy, thrombocytopenia, anemia and hyperbilirubinemia 2 months after starting leflunomide. Schistocytes were noted on peripheral smear and ADAMTS13 activity was low (< 5%), consistent with acquired TTP. He received therapeutic plasma exchange, corticosteroids, rituximab and caplacizumab with normalization of hemolysis labs and ADAMTS13 activity. However, pancytopenia persisted, raising the suspicion for leflunomide toxicity. Oral cholestyramine treatment was empirically started before teriflunomide (a leflunomide metabolite) level was found to be elevated. Blood counts normalized after cholestyramine and have remained normal at last follow-up over a year later. This is the first reported case of TTP precipitated by leflunomide. Our case highlights the importance of recognizing drugs as an etiology of TMA and adds leflunomide to this list.

DNA mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC) is found in about 15% of early-stage diseases and 5% of metastatic diseases. We reviewed a large, single-institutional database after implementation of universal reflex dMMR/MSI-H testing in CRC to compare profiles of younger (≤50) and older (50) patients.Between 2009 and 2017, all patients diagnosed with CRC at the University of Florida underwent reflex somatic tumor testing for dMMR by immunohistochemistry (MLH1, PMS2, MSH2, MSH6), MSI by PCR, and Next-Generation Sequencing. Statistical analysis was conducted with 2-sample comparison tests and logistic regression models.There were 375 patients included in the final analysis. Patients were grouped as younger (ages ≤50 years-old; n = 80) or older (50 years-old; n = 295). Compared to tumors from older patients, tumors from younger patients were less likely to be dMMR/MSI-H (12.5% vs. 21.4%, P = .013) and less likely to have a BRAF mutation (1.5% vs. 16.1%, P = .002). BRAF mutation status was highly associated with MMR status; BRAF-mutated tumors were 29.7 times more likely than BRAF-WT tumors to be dMMR/MSI-H (P = .001, 95% CI 11.3-78.3).Tumors of younger patients were less likely than tumors of older patients to have a dMMR/MSI-H or BRAF mutation. Universal MMR/MSI testing in our dataset identified a relatively large population of older patients with sporadic CRC who were eligible for immunotherapy.

Background:Advance directives are legal documents that include living wills and durable health care power of attorney documents. They are critical components of care for seriously ill patients which are designed to be implemented when a patient is terminally ill and incapacitated. We sought to evaluate potential reasons for why advance directives were not appropriately implemented, by reviewing the electronic health record (EHR) in patients with terminal cancer.Methods:A retrospective analysis of the EHR of 500 cancer patients from 1/1/2013 to 12/31/2016 was performed. Data points were manually collected and entered in a central database.Results:Of the 500 patients, 160 (32%) had an advance directive (AD). The most common clinical terminology used by physicians indicating a terminal diagnosis was progressive (36.6%) and palliative (31%). The most common clinical terminology indicating incapacity was altered mental status (25.6%), and not oriented (14%). 34 (6.8%) patients met all criteria of having a terminal diagnosis, a documented AD, and were deemed incapacitated. Of these patients who met all of these data points, their ADs were implemented on average 1.7 days (SD: 4.4 days) after which they should have been. This resulted in a total of 58 days of additional care provided.Discussion:This study provided insight on to how ADs are managed in day to day practice in the hospital. From our analysis it appears that physicians are able to identify when a patient is terminal, however, it is typically later than it should have been recognized. Further studies should be performed focusing on harnessing the power of the EHR and providing physicians formative and evaluative feedback of practice patterns to ensure that ADs are honored when appropriate.

Enfortumab vedotin (EV) is an antibody-drug conjugate with humanized anti-Nectin-4 antibody linked with a microtubule-disrupting agent called monomethyl auristatin E. Nectin-4 is a cellular adhesion protein that is overexpressed in urothelial cancer. EV was approved in December 2019 for patients with locally advanced or metastatic urothelial cancer who previously received platinum-based chemotherapy and immune checkpoint inhibitors. Here, we reviewed the clinical efficacy and safety data that led to the accelerated approval of EV for treating patients with metastatic urothelial cancer. Emerging clinical data on EV-based combinational therapeutic trials for metastatic urothelial cancer were also reviewed.

The treatment of colon cancer has had numerous recent advances, in terms of surgical approach, adjuvant therapies, and more. In this review, the authors examine randomized clinical trials comparing open surgery to laparoscopic surgery (including total mesocolic excision), and also examine the role of robotic surgery. Novel surgical techniques including the no-touch technique, side-to-side anastomosis, suture technique, complete mesocolic excision (CME) with central vascular ligation (CVL), and natural orifice transluminal endoscopic surgery (NOTES) are outlined. The role of placing endoscopic self-expandable metal stents (SEMS) for colonic obstruction is compared and contrasted with the surgical approach, and the effect that the anti-VEGF inhibitor bevacizumab may have on this side effect profile is further explored. The role of the resection of the primary tumor in the setting of metastatic disease is examined with respect to survival benefit. Pathways of perioperative care which can accelerate post-surgical recovery, including enhanced recovery after surgery (ERAS) are examined. The role of adjuvant chemotherapy in patients with high-risk stage II and patients with stage III disease is examined, along with the role on circulating tumor DNA (ctDNA) as well as with the biologic targeted agents cetuximab and bevacizumab. Lastly, the authors detail the postoperative surveillance schedules after surgical resection with respect to survival outcomes.

Objective/background: Clinical predictors of delayed engraftment following autologous hematopoietic cell transplantation (AHCT) are poorly described in the literature. The purpose of this study was to identify pretransplant characteristics contributing to delayed engraftment (DE) following AHCT. Methods: A retrospective, single institution study of 1162 consecutive patients undergoing AHCT from January 1996 to August 2016 was studied for DE. DE was defined as platelet count ≤ 50,000/µl, hemoglobin ≤ 8 g/dL, or absolute neutrophil count ≤ 1000/mm3. Results: Of the 1162 AHCT recipients, 263 (22.6%) were identified as having DE at 30-days post-AHCT with 80.0% being solely due to delayed platelet engraftment. Patients with Non-Hodgkin lymphoma (NHL) represented 18% of the original cohort, but accounted for 45% of those with DE, whereas multiple myeloma patients represented 59% of the initial cohort, but only 29% of those that had DE. At 3 months post-AHCT, transfusion dependence (p = .0083) prior to AHCT, low-infused CD34+ cell dose

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States. Although immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, the benefit in CRC has thus far been limited to patients with microsatellite instability high (MSI-H):DNA mismatch repair–deficient (dMMR) tumors. Recent studies in the refractory CRC setting have led to US Food and Drug Administration approvals for pembrolizumab as well as nivolumab (with or without ipilimumab) for tumors harboring an MSI-H:dMMR molecular profile. Several randomized controlled trials are underway to move immunotherapy into the frontline for metastatic cancer (with or without chemotherapy) and the adjuvant setting. Awareness of these studies is critical given the relatively low incidence (approximately 3%–5%) of MSI-H:dMMR in advanced or metastatic CRC to support study completion, because the results could be potentially practice changing. The real challenge in this disease is related to demonstrating the benefit of immunotherapy for the vast majority of patients with CRC not harboring MSI-H:dMMR. Given the rapid pace of scientific changes, this article provides a narrative review regarding the current landscape of immunotherapy for CRC. Particular attention is paid to the currently available data that inform today’s clinical practice along with upcoming randomized controlled trials that may soon dramatically change the treatment landscape for CRC.

Background Dipeptidyl peptidase 4 (DPP4) is a cell surface protein that can act as a tumor suppressor or activator, depending upon the level of expression and interaction with the microenvironment and chemokines. DPP4 inhibitors are used to treat diabetes. Methods We conducted this Surveillance Epidemiology and Endpoint Research‐Medicare database study to evaluate the role of DPP4 inhibitors on the overall survival (OS) of diabetic patients diagnosed with colorectal (CRC) and lung cancers. Results Diabetic patients with CRC or lung cancer who were treated with DPP4 inhibitors exhibited a statistically significant survival advantage (hazard ratio [HR] of 0.89; CI: 0.82‐0.97, P = 0.007) that remained significant after controlling for all other confounders. When DPP4 inhibitors were used in combination of metformin which is known to suppress cancer, the survival advantage was even more pronounced (HR of 0.83; CI: 0.77‐0.90, P

Although quinine is an infrequently prescribed drug, with malaria treatment being its only FDA-approved indication, unwitting exposure via beverages (e.g., tonic water), over the counter herbal remedies and illegal recreation drugs still occur. We present a unique case of a female patient who denied any known prior history of quinine exposure, who after being prescribed quinine tablets for restless leg syndrome, developed an immune-related thrombotic microangiopathy with thrombocytopenia and subsequent multi-organ failure. It was later elucidated that her only known potential source of prior quinine exposure was a remote history of crack-cocaine use. The patient survived this rare and severe inflammatory response with recovery of renal function and was able to discontinue dialysis.

Background Cluster of differentiation 26/dipeptidyl peptidase-4 (DPP4) is a cell surface glycoprotein with multifaceted roles, including immune regulation, glucose metabolism, and tumorigenesis. Recent literature has identified DPP4 inhibitors to improve survival in diabetic patients with prostate cancer. DPP4 inhibitors have been proposed to play a role in prostate cancer, as DPP4 is found at higher levels in malignant prostate tissue compared to benign and correlates with PSA levels and cancer stage. In this multi-center retrospective study, we aim to define the effects of DPP4 inhibitors on progression-free survival (PFS) in diabetic patients with advanced-stage prostate cancer. Methodology We performed a retrospective analysis of 161 patients with diabetes and advanced-stage (III or IV) prostate cancer at the University of Florida Health Cancer Center and Moffitt Cancer Center. Our cohort included 120 patients on metformin (control group) and 41 on a DPP4 inhibitor (study group). Results No significant difference in progression of prostate cancer was identified between those on DPP4 inhibitors versus metformin (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.64-1.61; p = 0.955). Median time to progression was 3.5 years (range: 2.4-4.6 years). Conclusions Despite prior literature indicating survival benefit of DPP4 inhibitors in prostate cancer, our study did not identify a statistically significant improvement of PFS in diabetic patients with advanced prostate cancer. Additional analysis with larger sample sizes and prospective investigation with study of tumor microenvironment are needed to evaluate clinical impact and potential survival benefit of DPP4 inhibitors in prostate cancer.

BackgroundIt is highly contested whether cytoreductive nephrectomy for treating advanced renal cell carcinoma (RCC) with sarcomatoid features (sRCC) benefits overall survival. Patients with sRCC are known to have a poor prognosis, and these tumors have a more aggressive biology than those without sarcomatoid features.MethodsPatients with clear cell RCC or non–clear cell RCC underwent cytoreductive nephrectomy in efforts to improve overall survival (OS). Patients were stratified by presence or absence of histologic sarcomatoid features within tumor samples.ResultsOf 167 patients who underwent cytoreductive nephrectomy, 127 had clear cell RCC, of whom 14 had sarcomatoid features, and 40 had non–clear cell RCC, of whom 13 had sarcomatoid features. Median age of the cohort was 62 years (range, 56.5–69 years). The cohort included 119 male (71.3%) and 48 (28.7%) female patients. Among all patients with advanced RCC, having sRCC had a significantly worse OS after cytoreductive nephrectomy (30 vs 8 months; hazard ratio [HR], 2.88; P P =0.00016). For patients with clear cell RCC, having sRCC conferred a significantly poorer survival (30 vs 9 months; HR, 2.82; P=0.0035). Patients with non–clear cell sRCC also had significantly worse outcomes compared to patients whose tumors did not have sarcomatoid features (30 vs 6.5 months; HR, 3; P =0.009). When patients with sRCC were stratified by whether there was >10% or ≤10% sarcomatoid features present within the sample, there was no significant difference in OS (8 vs 8.5 months; P =0.32).ConclusionsSarcomatoid features within tumor histology confer significantly poor prognosis. Patients with sRCC, regardless of clear cell vs non–clear cell histology, have significantly shorter OS. Even among patients with 10% or less sarcomatoid features, there was no OS benefit to cytoreductive nephrectomy. Based on our findings, there appears to be a limited to no role of cytoreductive nephrectomy if sRCC is identified on pretreatment biopsy. The role of radiomics and pre-operative biopsies may confer significant benefit in this patient population.

We hypothesized that concurrent angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) would improve outcomes in patients with metastatic urothelial carcinoma receiving PD1/L1 inhibitors by downregulating transforming growth factor β, a mechanism of resistance to PD1/L1 inhibitors. This retrospective study totaling 279 patients suggests potential additive or synergistic activity of ACEI/ARB with PD1/L1 inhibitors for metastatic urothelial carcinoma. BACKGROUND: The renin–angiotensin system is involved in the regulation of angiogenesis and cell proliferation. Angiotensin inhibition may improve drug delivery by enhancing tumor perfusion partly by downregulating transforming growth factor (TGF)-β. Because TGF-β is associated with resistance in patients with metastatic urothelial carcinoma (mUC) receiving programmed cell death protein 1/programmed cell death ligand 1 (PD1/L1) inhibitors, we hypothesized that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may enhance the outcomes of patients with mUC who receive PD1/L1 inhibitors. PATIENTS AND METHODS: Data from patients with mUC who received PD1/L1 inhibitors as monotherapy were obtained; patients from the Dana-Farber Cancer Institute constituted the discovery dataset, and data from Moffitt Cancer Center served as the validation dataset. A logistic regression investigated the impact of concurrent ACEI/ARB primarily on any regression of tumor (ART) after controlling for prognostic factors. RESULTS: Data were available for 178 patients from the discovery dataset, of whom 153 (86%) had received prior platinum and 33 (18.5%) concurrent ACEIs/ARBs. Multivariable logistic regression analysis revealed that ACEIs/ARBs were associated with greater probability of ART (odds ratio [OR] = 2.69; 95% confidence interval [CI], 1.15–6.30; P = .022). In the validation dataset, 101 patients were available, of whom 59 (58.4%) had received prior platinum and 22 (21.8%) concurrent ACEIs/ARBs. ACEI/ARB demonstrated a trend for association with ART (OR = 3.28; 95% CI, 0.98–10.99; P = .054) on multivariable analysis of the validation dataset. CONCLUSIONS: Concurrent angiotensin blockade was associated with a higher rate of tumor regression in patients with mUC receiving PD1/L1 inhibitors. Validation is warranted in a prospective trial, especially given the cost efficacy of ACEIs/ARBs.

OBJECTIVES To evaluate outcomes of patients achieving a post-treatment pathological stage of

BackgroundPenile squamous cell carcinoma (PSCC) is a rare malignancy, and those patients with metastatic disease have limited treatment options. Treatment is largely comprised of platinum-based chemotherapy; however, patients progressing after initial chemotherapy have a median overall survival (OS) of less than 6 months. Based on a high percentage of PD-L1 expression in patients with PSCC, and its biological similarities to other squamous cell carcinomas, we present two patient cases treated with pembrolizumab with extraordinary durable treatment response far beyond treatment with standard therapy.Main BodyThe first patient is a 64 year old male with PSCC who was treated with neoadjuvant chemotherapy, partial penectomy, and adjuvant radiation prior to developing metastatic disease. He had a high TMB (14 mutations/Mb) and was started on pembrolizumab with a complete response, which has been maintained for 38 months. The second patient is an 85 year old male with PSCC who was treated with partial penectomy and adjuvant chemotherapy and radiation prior to developing metastatic disease. He had positive PD-L1 expression CPS 130) and was started on pembrolizumab with a partial response, which has been maintained for 18 months after starting treatment.ConclusionsThese two cases of extreme durable response with pembrolizumab (with molecular data including TMB and PD-L1 status) represent a significant clinical benefit in this patient population. With limited treatment options that result in a median OS of less than 6 months, along with the toxicity profile of chemotherapy which may not be tolerated in elderly patients with comorbidities, this survival benefit with pembrolizumab, along with advances in tumor sequencing and clinical trials shows that there is a potentially significant benefit with novel therapies in this patient population.

Colorectal carcinoma is the second leading cause of cancer-related deaths in the United States, with rectal cancer accounting for approximately one third of newly diagnosed cases. Surgery remains the cornerstone of curative therapy, with total mesorectal excision being the standard of care. Although minimally invasive procedures might be appropriate for a subset of patients with early-stage, superficial tumors, the standard of care for medically operable patients with nonmetastatic rectal cancer includes a comprehensive multimodality approach of neoadjuvant chemoradiotherapy, surgery with total mesorectal excision, and systemic chemotherapy. However, the morbidity and mortality related to both local and distant organ relapse have remained challenging. In the present review, we have discussed the trial-level evidence that has shaped the current clinical practice patterns in the treatment of curable, nonmetastatic rectal cancer. In addition, we have discussed the anticipated results of ongoing clinical trials and outlined pragmatic opportunities for future investigation to optimize the current status quo and, hopefully, provide prospective validation of novel approaches in the treatment of rectal cancer.

Background: Dipeptidyl peptidase-4 (DPP4), a cell surface protein, exhibits a crucial role in tumor biology and regulation of the immune system. We aim to study the impact of DPP4 inhibitors (DPP4i) in patients with prostate cancer (PRC), pancreatic cancer (PC) and breast cancer (BC). Methods: Using the SEER and Medicare linked database, we identified patients with PRC or PC or BC with coexisting type II diabetes mellitus between 2007 and 2015. Patients were classified into four groups: (1) not on either DPP4i or metformin (reference group), this group included patient that were on anti-diabetic agents other than metformin or DPP4i (2) metformin only, (3) DPP4i only, and (4) DPP4i along with metformin (combination group). Overall survival (OS) analyses were performed using SAS®, version 9.4. Results: We identified 15,330 patients with PRC, 5,359 patients with PC and 16,085 patients with BC. In PRC cohort, patients on DPP4i had significant survival advantage with HR 0.77 (95% CI: 0.64–0.93), P = 0.005 when compared to the reference group. Patients taking metformin also had significant OS benefit with HR 0.87 (95% CI: 0.81–0.93), P < 0.0001 when compared to the reference group. However, in BC cohort, OS did not favor the patients taking DPP4i with HR 1.07 (95% CI: 0.93–1.25, P = 0.33). Similarly, in PC cohort, OS was indifferent for the patients on DPP4i with HR 1.07 (95% CI: 0.93–1.24, P = 0.68). Upon subgroup analyses of PRC patients, the survival favored the group taking DPP4i, irrespective of stage, use of chemotherapy, androgen-deprivation therapy, and prostatectomy or radiation therapy. Conclusions: DPP4i seems to improve survival in PRC patients; however, not in PC or BC patients. While the exact mechanism involved remains to be elucidated, a prospective clinical trial would help to confirm these findings.

Background Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following transplant (solid organ or allogeneic) due to the proliferation of lymphoid cells in the immunosuppressed state. The incidence of PTLD follows a bimodal distribution, with high incidence immediately after transplant (early-onset PTLD), followed by a decline and then a high-incidence again five years after transplantation (late-onset PTLD). This study exclusively aims to identify prognostic factors for the subgroup of PTLD, described as very late-onset PTLD, occurring after 10 years of transplant. Methods This study was conducted at the University of Florida, with the requisite study population identified through the cancer registry. Data were collected by individual chart review and analyzed. Survival estimates and univariate and multivariate analyses were performed to measure the effects of each variable on overall survival. Results A total of 33 patients were identified, with a median age at transplant of 42.3 years, while the median age at PTLD diagnosis was 54.7 years. Median time from transplant to PTLD diagnosis was 13.3 years. Kidney (30.3%), liver (27.3%), and heart (24.2%) transplants were the most common allografts associated with very late PTLD development. The most common pathology was diffuse large B-cell lymphoma (DLBCL) in 45.5% of patients. CHOP+/-R (cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), prednisone, rituximab) was the most common chemo regimen used as the initial choice in 36.4% of patients. Median survival was 5.4 years. Univariate analysis showed that age at diagnosis over 65, male gender, bone marrow involvement, past medical history (PMH) of malignancy, immunosuppression regimen at PTLD diagnosis, and initial and final best response to treatment were statistically significant (p

e16546 Background: Radium-223 (Xofigo) has been shown to increase overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) via the phase 3 ALSYMPCA study. The side effect of persistent pancytopenia was noted in 2% of the patients, however, the incidence seen in our institutional clinical practice is higher than reported in the literature. This analysis serves to identify predictive factors and thereby help impact future therapy directions in this patient population. Methods: A retrospective analysis was performed analyzing patients with mCRPC who received xofigo at UFHealth in a 3 year span (from January 2014 to January 2017). Data collected included CBC, ECOG functional status, kidney and liver function, evidence of bony disease on imaging, prior chemotherapy regimens, total radiation dose, and PSA. This study was IRB approved. Results: 52 patients with mCRPC were identified, 27 of which received xofigo. 23 patients received treatment at UF, and one was lost to follow-up. 16 patients (73%) completed the full course (6 doses) of xofigo, while 6 did not. 10 patients (45%) developed pancytopenia, with 2 recovering counts within eight months while the other 8 had persistent cytopenias (6 of which were transfusion-dependent). Older age (74.0 ± 8.8 vs 68.7 ± 10.2) and higher ECOG score (1.6 ± 0.7 vs 1.2 ± 0.6) correlated with increased risk of pancytopenia. In addition, a higher percentage of patients who received prior radiation therapy were more likely to develop pancytopenia (90% vs 75%). All patients studied had bony disease and received prior chemotherapy. Conclusions: Albeit with a limited sample size, we found a higher rate of xofigo-induced pancytopenia in our patient population than the 2% reported in the literature. This may influence clinical decision making in the treatment of mCRPC, as pancytopenia may preclude patients from other survival-prolonging therapies. Factors such as age, functional status, and prior radiation therapy are important to keep under consideration prior to xofigo treatment. Additional larger studies are necessary to further quantify this effect.

485 Background: The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. Angiotensin pathway inhibitors are postulated to favorably reprogram the stroma in part by inhibition of transforming growth factor-β, a major mechanism of resistance, and have been previously reported to be associated with improved outcomes in the setting of immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (Jain R, Clin Genitourin Cancer 2021). In this analysis, we examined the association of angiotensin inhibitors in the setting of NAC for MIBC preceding radical cystectomy (RC). Methods: Pts with MIBC who received NAC preceding radical cystectomy were assembled from 3 institutions: Dana-Farber Cancer Institute (DFCI), Moffitt Cancer Center (MCC) and McGill University Health Center (MUHC). Pts were retrospectively assessed for the association of concurrent ACEi/angiotensin receptor blockers (ARB) use at initiation of NAC on pathologic complete response (pCR), defined as pT0N0, and overall survival (OS). Pathologic features, performance status (PS), clinical stage, type/number of cycles of NAC, and toxicities were collected. The Kaplan-Meier method was used to estimate OS. Logistic and Cox regression were used to explore factors potentially prognostic for pCR and OS respectively. Results: 302 MIBC pts who received NAC preceding RC were available from 3 institutions: DFCI (n = 187), MCC (n = 50) and MUHC (n = 65). Overall, 141 pts (46.7%) received Cisplatin/Gemcitabine, 130 (43.1%) received dose dense MVAC and the remaining received other regimens. The overall pCR rate was 26.2%. The 5-year OS was 62%. 63 (20.9%) pts were receiving an ACEi and 41 (13.6%) were receiving an ARB. ACEi prior to NAC approached significance for association with pCR (odds ratio = 1.71 (95% CI = 0.94-3.11) p = 0.077). Pts with cT3/4N0-N1 disease receiving ACEi had higher pCR rates (30.8% (8/26) vs 17.7% (14/98), p = 0.056) than those not on ACEi; no difference was observed for pts with cT2N0 tumors (31.1% vs 31.3%, p = 0.99). pCR, ECOG-PS and clinical stage were significantly associated with improved OS. ARB intake was not associated with pCR or OS. Conclusions: ACEi intake appeared potentially associated with increased pCR in pts with MIBC receiving NAC, which was more pronounced in those with higher clinical stages cT3/4N0-1. Given the association of pCR with OS, our data suggest the potential relevance of angiotensin as a therapeutic target in aggressive MIBC. Future prospective validation is warranted to repurpose angiotensin inhibitors in this setting, given their excellent toxicity profile and low costs.

Pancreatic cancer is often diagnosed at late stages, where disease is either locally advanced unresectable or metastatic. Despite advances, long-term survival is relatively non-existent. This review article discusses clinical factors commonly encountered in practice that should be incorporated into the decision-making process to optimize patient outcomes, including performance status, nutrition and cachexia, pain, psychological distress, medical comorbidities, advanced age, and treatment selection. Identification and optimization of these clinical factors could make a meaningful impact on the patient’s quality of life.

Background Post-transplant lymphoproliferative disorder is a well-recognized but rare complication of hematopoietic stem cell and solid organ transplant. Due to rarity of this disease, retrospective studies from major transplant centers has been the main source to provide treatment guidelines, which are still in evolution. The sample size of this study is among one of the largest study on PTLD till date reported throughout the world. Methods This study was performed at University of Florida which is one of the largest transplant center in South East United States. We performed treatment and survival analysis along with univariate and multivariate analysis to identify prognostic factors. Results We reviewed 141 patients diagnosed with PTLD over last 22 years with median follow-up of 2.4 years. The estimated median overall survival of the entire group was 15.0 years. Sub group analysis showed that 5-year overall survival rates of pediatric population were 88% (median not reached). For adults, median OS was 5.35 years while for elderly patients it was 1.32 years. The estimated median OS of patients with monomorphic PTLD was 9.0 years while in polymorphic PTLD was 19.3 years. Univariate analysis identified gender, age at transplant and PTLD diagnosis, performance status, IPI score, allograft type, recipient EBV status, multiple acute rejections prior to PTLD diagnosis, PTLD sub-type, extra-nodal site involvement, immunosuppressive drug regimen at diagnosis, initial treatment best response were statistically significant prognostic factors (p

Introduction Absolute lymphocyte count (ALC) recovery following autologous stem cell transplant(ASCT) has been shown to be an important factor for overall and progression free survival. This is thought to be mediated by improved immune reconstitution resulting in decreased adverse events. Objectives Our primary aim was to investigate the role of ALC recovery at day 30 (D30) following ASCT in the overall survival(OS) and progression free survival(PFS) in patients treated for multiple myeloma(MM). Our secondary aim was to evaluate the correlation between infused CD3 content and ALC D30. Methods Two hundred forty-six patients were identified from our center's CIBMTR database who underwent ASCT between 2000-2010 for MM. Following manual chart review one hundred twenty-five met criteria for inclusion in analysis. ALC D30 was defined as the closest ALC to D30 post ASCT +/- 7 days. Patients who did not have D30 ALC data (n= 87) or underwent tandem ASCT (n=25) were excluded. Descriptive data is available in Table 1. The cohort was split into two groups with ALC ≥ 500 cells x10^6/cu mm or ALC Results ALC D30 failed to show an association with either PFS or OS in the univariable and multivariable analyses. The Median PFS time in ALC ≥500 group was 23.7 months (95%CI: 18.4 - 29.7) compared to 30.1 months (95% CI: 15.5 – 70.5) in the ALC Conclusions Our study failed to show an association between ALC D30 recovery and OS or PFS in patients with MM undergoing ASCT. Previously identified factors such as age also did not show an association with OS and PFS in our study. Data on induction regimens was not collected for this study and maintenance therapy was not administered or data was unavailable for a large portion of our dataset which may contribute to the discrepancy with previously reported studies. CD3+ dose of cells infused showed a weak but statistically significant correlation with ALC D30.

Introduction PTLD is the most frequent malignancy following SOT in children and the second most common SOT complication in adults. However, factors determining outcomes in children are poorly understood due to its relative rarity. Methods This study was performed at the University of Florida. Univariate and multivariate analyses were used to identify prognostic factors in pediatric patients diagnosed with PTLD. Results We reviewed records of 54 pediatric (younger than 18 years old at diagnosis) patients diagnosed with PTLD from 1994 to 2017. The median follow-up was 28.8 months. The estimated 5-year survival rate was 87.6% (95% CI 74.3-94.2%). Univariate analysis showed that organ transplanted (specifically heart transplant), poor response to initial treatment, allograft rejection, and low Karnofsky score were statistically significant for negative prognostic factors in determining survival. Multivariate analysis determined progression in response to initial treatment and presence of allograft rejection as statistically significant prognostic factors affecting overall survival. We found no statistically significant impact of EBV serological status on PTLD prognosis. Conclusions Disease progression and allograft rejection were strong negative prognostic indicators in our study cohort. Close attention to graft status and development of therapies that protect the graft from rejection while bolstering anti-EBV immunity will be essential to further improving PTLD outcomes in children.

Introduction Multiple primary malignancies (MPMs) are seen in ~5% of all tumors. The aim of this study was to determine the quantitative impact on overall survival (OS) and treatment choices in patients with MPMs. Methods A retrospective analysis to determine patients with MPMs was conducted over a six-year period. Patients were defined as simultaneous MPMs if the second malignancy was discovered within 60 days of the first, and as sequential MPMs if discovered after 60 days of the first. Results Fifty-six patients with MPMs as defined above were identified, 38 (68%) simultaneous and 18 (32%) sequential. Development of second malignancy did not affect treatment in 47 (84%) of patients. Median OS after diagnosis of first malignancy was 13.0 months (95% confidence interval (CI) 10.3-15.8 months), compared to 10.6 months (95% CI 7.1-13.9 months) after the diagnosis of second malignancy. Median OS for the simultaneous MPM group was 13.5 months (95% CI 7.1-19.9 months), compared to 3.2 months (95% CI 0.0-9.8 months) for the sequential MPM group. Conclusions The development of a second malignancy impacts OS and treatment decisions. Patients who developed sequential MPM performed poorer than those who developed simultaneous MPM. This was likely in part due to effects of existing treatment on performance status as well as treatment preferences when second MPM is diagnosed (as many patients opted for supportive care after second MPM). Further analysis with larger patient cohorts is necessary to ascertain the aforementioned effects of OS and treatment options with respect to tumor pathology, stage, and performance status.

e16558 Background: Cyclooxygenase (COX) inhibition is postulated to restore the immune environment and synergizes with immune checkpoint inhibitors (ICI). The concurrent use of COX inhibitors (COXi) and ICI was associated with longer disease control in metastatic melanoma and non-small cell lung cancer. However, its role in mRCC remains unclear. Methods: We retrospectively reviewed 194 patients with mRCC treated with ICI (PD-(L)1 inhibitors +/- CTLA-4 inhibitors or TKIs) at Moffitt Cancer Center between 6/2014-7/2019. Concurrent use of COXi (aspirin [ASA] or NSAIDs) was defined as at least 3 weeks of COXi use during the first ICI course. Clinical characteristics of both arms were compared using Chi-squared or Kruskal-Wallis Rank Sum test. Time to progression (TTP) and Overall survival (OS) were compared using Kaplan Meier’s estimates. Univariate and multivariate Cox proportional hazards model was performed to evaluate the association between clinical factors, TTP, and OS. Results: Of 194 patients, 126 patients (64.9%) took COXi. Median age was 59.7 years and 80.4% were male. COXi arm had fewer patients with < 1 year from diagnosis to systemic treatment (45.9% vs 69.5%, p = 0.006) and more advanced age (median: 66 years vs 60 years, p = 0.01). IDMC risk group, number of prior therapies, neutrophil to lymphocytes ratio were similar between both arms. Median TTP was 8 months (m) for COXi arm and 12m for ICI only (HR 1.38; 95% CI [0.98, 1.94]). Median OS was 27m for COXi arm and 33m for ICI only (HR 1.05, 95% CI [0.69, 1.59]). Early mortality rate (within 3m of ICI treatments) were similar between both arms. Conclusions: In contrast to melanoma and lung cancer, concurrent use of COXi and ICI did not improve TTP and OS in patients with mRCC. The dual blockade showed a trend for shorter TTP. Further validation studies with larger cohorts are needed to confirm this finding.[Table: see text]

472 Background: Enfortumab Vedotin (EV), an antibody-drug conjugate that targets nectin-4, is approved for metastatic urothelial carcinoma (mUC) progressing post-platinum and PD1/L1 inhibitor therapy. Erdafitinib is approved in patients for post-platinum mUC with activating genomic alterations in FGFR2/3, but the activity of EV in this subset is unclear. We investigated the activity of EV in patients (pts) with mUC based on FGFR2/3 genotype to inform management. Methods: In this multi-center, retrospective analysis, we assessed the objective response rate (ORR) to EV in mUC pts with and without FGFR2/3 genomic alterations detected by targeted panel next-generation sequencing. Activating gene fusions and known hotspots mutations in the two genes were considered. Descriptive analysis of ORR and patient characteristics was performed. Fisher’s exact test and binomial test with two-tailed p-value were used. Results: 40 pts were available from 4 institutions. Most pts were male (31/40, 78%) and the median age at start of EV was 74.1 (range 49 – 90) years. Ten patients (25%) had upper tract urothelial carcinoma (UTUC), and 33 (82%) had baseline ECOG performance status of 0-1. 31 of 39 patients had received both platinum-based chemotherapy and PD1/L1 inhibitors. Seven patients had confirmed activating hotspot FGFR3 mutations (p.S249C or p.Y373C). One pt had FGFR2 high-level amplification (HA), and one had FGFR3 HA. Of 36 patients evaluable for ORR, 18 had partial response (PR), 12 had stable disease (SD) and 6 had progressive disease (PD). Patients with FGFR2/3 activating mutations exhibited an ORR that was not statistically different compared to patients without no mutations: 2/7 (29%; 90% CI: 5 – 66%) vs. 16/29 (55%; 90% CI: 38 – 71%) respectively ( p-value = 0.4). 3/7 patients with FGFR3 hotspot mutations received an FGFR2/3 inhibitor and none responded; one of them had a sequential response to EV. Conclusions: In this multi-center retrospective cohort, FGFR2/3 activating genomic alterations did not appear to compromise response to EV in mUC. Larger studies are required to confirm our findings and optimal sequencing of EV and erdafitinib in mUC pts with FGFR2/3 genomic alterations requires further assessment.

453 Background: The renin-angiotensin system (RAS) is involved in regulation of angiogenesis and cell proliferation. Preclinical data also indicate that angiotensin inhibition may improve drug delivery by enhancing tumor perfusion partly by downregulating transforming growth factor (TGF)-β. Since (TGF)-β appears to be associated with resistance in patients (pts) with metastatic urothelial carcinoma (mUC) receiving PD1/L1 inhibitors, we hypothesized that angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) may enhance the outcomes of mUC pts receiving PD1/L1 inhibitors. Methods: Data from mUC pts who received PD1/L1 inhibitors as monotherapy were obtained: pts from the Dana-Farber Cancer Institute (DFCI) served as the discovery dataset, while data from Moffitt Cancer Center (MCC) served as the validation dataset. Data for ACEI and ARB administration was collected with concurrent administration defined as ongoing therapy from the time of starting PD1/L1 inhibitor treatment. A logistic regression was used to investigate the impact of concurrent ACEI/ARB on any regression of tumor (ART, any decrease in size of tumor on scan) as the primary endpoint defined as any tumor regression after controlling for known prognostic factors (performance status, sites of metastasis, neutrophil/lymphocyte ratio, platelet count, hemoglobin). Overall survival (OS), the secondary endpoint, was analyzed using Cox proportional hazards regression. Results: Data was available for 178 pts from DFCI (discovery dataset) with mUC who received a PD1/L1 inhibitor of whom 153 (86%) had received prior platinum and 33 pts (18.5%) received concurrent AECI/ARBs. Multivariable analysis controlling for known prognostic factors revealed that patients who received ACEIs or ARBs had greater ART (HR 3.0 [95% CI 1.25-7.17], p = 0.014) and improved OS, (HR 0.49 [95% CI 0.28-0.88] p = 0.016). In the MCC validation dataset, 101 pts were available of whom 59 (58.4%) had received prior platinum and 22 pts (21.8%) received concurrent ACEI/ARBs. Univariate analysis showed that those patients who were treated with ACEI/ARB had an improved ART (OR 3.32 [95% CI 1.22-9.06] p = 0.019). On multivariable analysis, there was a borderline significant association of ACEI/ARB with ART (OR = 3.03, p = 0.075), but no association was observed with OS. Conclusions: In this hypothesis-generating study, concurrent angiotensin inhibitors including ACEI or ARBs were associated with tumor regression in mUC pts receiving PD-1/L1 inhibitors. The inconsistent association with OS may be partly due to modest sample size and comorbidities associated with the need for ACEI/ARBs. These results require validation in a prospective study.

109 Background: Dipeptidyl peptidase IV (DPP4), also known as Cluster of differentiation 26 (CD26) is a commonly expressed cell surface protein found in many cell types that can function as a tumor suppressor or activator, depending on the cancer type its interactions with the tumor microenvironment. DPP4 has been studied as a tumor biomarker due to its expression in various primary tumors and metastases. Recent literature established benefits of DPP4 inhibitors on progression free survival (PFS) of diabetic patients with advanced colorectal and airway cancers. In this study, we examine the effect of DPP4 inhibitors on PFS in diabetic patients (pts) with advanced-stage prostate cancer. Methods: We performed a multi-center retrospective analysis at Moffitt Cancer Center and the University of Florida of diabetic pts with advanced stage (III or IV) prostate cancer. All pts were on anti-hyperglycemic therapy and received either surgery, radiation therapy, or both for their prostate cancer. The control group included pts on metformin and a sulfonylurea, and the study group included pts on a DPP4 inhibitor and metformin. PFS was calculated for both groups, and Cox proportional hazards regression was used to determine statistical significance. Kaplan-Meier survival analysis was done to predict the effect of DPP4 inhibition and radiation therapy on PFS. Results: Our study population consisted of 161 pts, with 120 pts in the control group and 41 in the study group. No significant difference in progression of prostate cancer was found between those on DPP4 inhibitor vs. Metformin. Specifically, 24 of 41 (59%) of patients on DPP4 inhibitors progressed, while 73 of 120 (61%) of patients on Metformin had progression of prostate cancer (HR 1.01, 95% CI 0.64 to 1.61, p= 0.955). Median time to progression was 3.3 years in the DPP4 group versus 3.5 years in the Metformin group. However, radiation therapy was associated with improved PFS (HR 0.56, 95% CI 0.37 to 0.84, p= 0.0006). Conclusions: Contrary to what has been shown in pts with diabetes and advanced colorectal or airway cancers, exposure to DPP4 inhibitors did not lead to statistically significant improvement in PFS in pts with advanced stage prostate cancer. Recent data suggests that DPP4 may act as a tumor suppressor gene to the androgen receptor (AR) pathway, and that DPP4 inhibition can result in emergence of resistance to androgen deprivation therapy (ADT). Further analysis with larger sample sizes is necessary to elucidate if this is applicable to prostate cancer as a whole, or if this effect is specific to castrate-sensitive prostate cancer (CSPC) vs. castrate-resistant prostate cancer (CRPC).

Primary care physicians and cardiologists rely on risk scoring systems, which consist of a number of clinical variables used together, to predict stroke risk in patients with atrial fibrillation (AF). Ultimately, this helps in determining the need for anticoagulation. Left atrial size is not used in any stroke risk scoring system to stratify patients at risk for cardioembolic stroke. Throughout the literature, there is much debate surrounding the use of left atrial size as an additional risk factor for stroke in patients with and without AF. This review summarizes the stroke risk scoring systems in the currently available literature and the increasing risk of stroke associated with left atrial size. In conclusion, the authors propose the consideration of a tool to incorporate both the best available stroke risk scoring systems and the left atrial size, for a better risk assessment and management of AF.

Introduction. Ibrutinib is commonly used for the treatment of patients with CLL in either first-line or relapsed/refractory settings. Case Presentation. We present the case of a 74-year-old Caucasian man with CLL who presented with penile gangrene upon initiation of ibrutinib treatment. Our case is the first showing the complication of penile gangrene associated with ibrutinib use. The gangrene was self-limited upon discontinuing ibrutinib. Conclusion. Our finding describes a very rare yet important adverse event associated with ibrutinib use.

Sporothrix schenckii is a pathogen with a predilection for dissemination in immunocompromised individuals, often with HIV. We report a case of disseminated sporotrichosis in an unfortunate 25 year old male (without HIV) who was originally treated for presumed pneumonia. The patient continued to worsen clinically and further work-up eventually revealed Sporothrix schenckii species with involvement of multiple organs including the skin, heart, lungs and bone marrow. Despite treatment with multiple antibacterials and antifungals, he ultimately passed away. This case illustrates the aggressive nature of this disease along with the importance of early/proper diagnosis and treatment.

e24011 Background: Advanced care planning and living wills are critical components of caring for patients at the end of their lives. Advance directives are designed to be implemented when a patient meets the legal definition of terminal and is deemed incapacitated. By reviewing the electronic health record (EHR) in patients with terminal cancer, we sought to evaluate whether advance directives were appropriately implemented. Methods: A retrospective analysis of the EHR of 500 cancer patients from 1/1/2013 to 12/31/2016 was performed. Data points were manually collected and entered in a central database, and data analysis was completed using SAS. Results: Of the 500 patients, 160 (32%) had an advance directive (AD). The most common clinical terminology used by physicians indicating a terminal diagnosis was “progressive” (36.6%) and “palliative” (31%). The most common clinical terminology indicating incapacity was “altered mental status” (25.6%), and “not oriented” (14%). 34 patients (6.8%) met all criteria of having a terminal diagnosis, a documented AD, and deemed incapacitated. Of these patients who met all of these data points, their ADs were implemented on average 1.7 days (SD: 4.4 days) after which they should have been. This resulted in a total of 58 days of additional care provided to these patients. Conclusions: End-of-life care is a challenging albeit vital part of the practice of medicine. This study provided insight on to how ADs are managed in day to day practice in a hospital. From our analysis, it is clear that physicians are able to identify when a patient is terminal; however, it is typically later than it should have been recognized (and thereby, leading to delays in the implementation of the patient’s AD). Further studies should be performed focusing on harnessing the power of the EHR and providing physicians formative and evaluative feedback of practice patterns to ensure that ADs are honored when appropriate.

5043 Background: Pathologic complete response (pCR) after NAC for MIBC is strongly correlated with long-term overall survival. However, there are sparse data on the risk of recurrence based on depth of pathologic response (pT0, pTa, pTis, pT1), and the differential impact of clinicopathologic factors and NAC regimen on recurrence. Methods: Baseline data on all pts with cT2-4N0-1 MIBC receiving NAC and who achieved < ypT2N0 disease at radical cystectomy (RC) from 9 international centers were obtained. The key outcome was time to recurrence (TTR) – defined as the time to any recurrence in the urinary tract or regional/distant metastasis, with death (in the absence of recurrence) considered a competing risk. Cox regression analysis was used to analyze the impact of clinical factors on recurrence. Results: A total of 506 pts were available. Median age was 66 years (range 33-86) and 78% (n = 396) were male; median follow-up after RC was 2.6 years. The majority of patients had pure urothelial histology (n = 371, 73%), and baseline stage was cT2N0 (n = 368, 73%), cT3-4N0 (n = 95, 19%) and TanyN1 (n = 43, 9%). NAC regimens were gemcitabine-cisplatin (GC, n = 296, 59%), dose-dense methotrexate-vinblastine-doxorubicin-cisplatin (ddMVAC, n = 141, 28%), split-dose GC (n = 29, 6%), MVAC (n = 29, 6%) and non-cisplatin based regimens (n = 11, 2%). At RC, 304 patients (60%) had ypT0N0 disease, 32 (6%) had ypTaN0, 107 (21%) had ypTisN0 and 63 (13%) had ypT1N0. Overall, 43 patients (8%) recurred with a median TTR of 56 weeks (range 7-251); 5-year freedom from recurrence was 87% (95% CI 83-91). The majority (n = 38) recurred outside the urinary tract. On multivariable analysis, ypTa (HR = 3.36 [1.24-9.11]) and ypT1 (HR = 2.88 [1.33-6.22], p = 0.013) disease at RC were predictors of shorter TTR, while female sex was associated with longer TTR (HR = 0.52 [0.27-0.98], p = 0.043). The type of NAC was not predictive of TTR (GC vs. other, HR = 1.49 [0.75-2.97], p = 0.26). Conclusions: To our knowledge, this is the largest study to quantify the risk of recurrence in pts achieving pathologic response after NAC and RC for MIBC. 8% of patients undergoing NAC and achieving < ypT2N0 at RC recurred. Residual ypTa and ypT1 disease conferred a significantly higher risk of recurrence, while ypTis did not; female sex was associated with a lower risk of recurrence. Importantly, the type of cisplatin-based NAC regimen used was not an independent predictor of recurrence.

Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase IV (DPP4), is a cell surface protein with exopeptidase activity and is expressed by most cell types. CD26/DPP4 is a multifunctional molecule with diverse biological effects, including regulatory effects on tumor growth, invasion and metastasis, and is a potential novel therapeutic target for selected cancers. In this study, we retrospectively analyzed diabetic patients with concurrent advanced airway or colorectal cancer to examine the effect of DPP4-inhibitors on progression-free survival (PFS). We performed a multi-center retrospective review of patients with advanced colorectal or airway (lung, head and neck) cancer and a concurrent diagnosis of diabetes. The control group included patients on metformin and a sulfonylurea, and the study group included patients on metformin and a DPP4 inhibitor. Ninety-six patients were eligible for the study. The cancers progressed in 23.7% of patients treated with DPP4 inhibitors compared to 50.9% of patients in the control group with an odds ratio of 0.303 [95% confidence interval (CI): 0.106-0.809] and P=0.010. There was a statistically significant improvement in PFS in the study group as compared to the control group, hazard ratio=0.42 (95% CI: 0.21-0.84) and P=0.014. There was a trend toward improvement in overall survival, although this effect was not statistically significant (P=0.11). Exposure to DPP4 inhibitors in the study group led to higher PFS in patients with advanced colorectal and airway cancers. Additional investigations with larger patient cohorts are needed to validate the relationship between DPP4 inhibition and the clinical outcome of selected malignancies.

A 52-year-old man presented to our hospital for further workup of fever of unknown origin after an extensive workup at an outside hospital had failed to reveal a diagnosis. At the outside hospital, he underwent excisional biopsy of the left supraclavicular lymph node, which showed non-necrotising granulomatous changes, and a bone marrow biopsy which showed a normocellular marrow. He was discharged without a diagnosis with recommendations to present to a tertiary hospital. During his admission, his hospital course was complicated by new direct hyperbilirubinaemia and eosinophilia, prompting liver and skin biopsies which showed CD30+ and CD3+ cells. He subsequently underwent left axillary lymph node biopsy, which was reported as ‘classic Hodgkin’s lymphoma’. With worsening lab values and T cells noted on liver and skin biopsies, excisional lymph node biopsy was sent to the National Institute of Health, where it was confirmed patient had peripheral T cell lymphoma.

Racial disparities in transcatheter aortic valve replacement (TAVR) implantation results from several factors, including socioeconomic disparities, inherent biases in healthcare provision, fewer referrals to specialists and language barriers in some minority populations. In this review article, we discuss the current data on the racial disparities in TAVR, explore the prevalence of aortic stenosis in different demographics in the United States and we proffer practical solutions to these problems.

Coronary artery disease (CAD) is a major cause of cardiovascular death worldwide. Prevalence of CAD is highly variable among different races. Asian Indians have been noted to have the highest CAD rates and the conventional risk factors fail to explain this difference completely. Asian Indians constitute a fifth of the global population, and the higher rates of CAD in this population constitute a major health challenge. There have been studies in the early 2000s that investigate the risk factors in this population; however, very few studies have been done since then that explore the higher CAD rates in Asian Indians. This is a comprehensive and current review of the known risk factors for CAD in Asian Indians and strategies physicians should consider relieving this burden.

Extra gonadal germ cell tumors have variable clinical presentations and locations. We report a case of an extra-gonadal germ cell tumor in a 26-year-old male who presented with chest pain. Imaging revealed a large pericardial effusion with underlying mass invading the pericardium. Pericardial effusion is an extremely rare initial site of diagnosis or site of metastasis for malignancy. This case illustrates the importance of a thorough history and physical examination, broad differential diagnosis, and to keep in mind serious complications from rare presentations of disease.