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We present here the second documented case of severe immune checkpoint inhibitor-induced myocarditis successfully treated with abatacept. The patient was started on pembrolizumab for stage IIIA malignant melanoma, and after the first dose was admitted for worsening shortness of breath and weakness. Her symptoms were refractory to high-dose steroids and she decompensated rapidly necessitating cardiopulmonary resuscitation and subsequent intubation and mechanical ventilation. Intravenous immunoglobulin and plasmapheresis did not invoke significant improvement, so abatacept was then initiated. She began to show improvement and was eventually discharged to a skilled nursing facility. This case highlights a severe adverse reaction to an immunomodulator class steadily growing in its application. Providers of all specialties should be aware of the side effects and treatment options. Our case demonstrates that continued investigation into the utilisation of CTLA-4 agonists in the treatment of severe adverse reactions like myocarditis caused by pembrolizumab is required.

BACKGROUND: National-level data of cancer patients’ readmissions after ST-segment elevation myocardial infarction (STEMI) are lacking. OBJECTIVES: The primary aim of this study was to compare the rates and causes of 30-day readmissions in patients with and without cancer. METHODS: Among patients admitted with STEMI in the United States National Readmission Database (NRD) from October 2015–December 2017, we identified patients with the diagnosis of active breast, colorectal, lung, or prostate cancer. The primary endpoint was the 30-day unplanned readmission rate. Secondary endpoints included in-hospital outcomes during the index admission and causes of readmissions. A propensity score model was used to compare the outcomes of patients with and without cancer. RESULTS: A total of 385,522 patients were included in the analysis: 5956 with cancer and 379,566 without cancer. After propensity score matching, 23,880 patients were compared (Cancer = 5949, No Cancer = 17,931). Patients with cancer had higher 30-day readmission rates (19% vs. 14%, p < 0.01). The most common causes for readmission among patients with cancer were cardiac (31%), infectious (21%), oncologic (17%), respiratory (4%), stroke (4%), and renal (3%). During the first readmission, patients with cancer had higher adjusted rates of in-hospital mortality (15% vs. 7%; p < 0.01) and bleeding complications (31% vs. 21%; p < 0.01), compared to the non-cancer group. In addition, cancer (OR 1.5, 95% CI 1.2–1.6, p < 0.01) was an independent predictor for 30-day readmission. CONCLUSIONS: About one in five cancer patients presenting with STEMI will be readmitted within 30 days. Cardiac causes predominated the reason for 30-day readmissions in patients with cancer.

Background Ibrutinib is a Bruton’s tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown. Objective This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD. Methods A single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. The predictors of atrial arrhythmia (namely atrial fibrillation) were assessed using logistic regression. A Cox-Proportional Hazard model was created for mortality. Results Patients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. There were no differences in risk of bleeding or discontinuation between the two cohorts. Conclusions Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

Introduction: The development of hepatocellular carcinoma (HCC) is associated with underlying chronic liver disease from viral hepatitis or nonviral etiologies, such as nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease. An area of current research interest is the relationship between etiology of chronic liver disease in HCC patients and the response to specific treatment modalities. The purpose of this study is to identify prognostic indicators and compare survival outcomes among HCC patients within an Appalachian patient population. Methods: A single-institution, retrospective chart review was conducted for all patients diagnosed with HCC between August 2009 and March 2017 at West Virginia University Hospital. Patient demographics, tumor characteristics, laboratory data and treatment information were obtained from the electronic medical record (EMR). Survival analyses were performed using Kaplan-Meier method and multivariable Cox regression analysis. Results: The study sample (n=100) had a mean age of 62 years and was comprised of 82% males and 18% females. Nonviral etiologies of chronic liver disease were predominant (55%) over chronic viral hepatitis (45%). Significant adverse prognostic indicators of overall survival (OS) were Child-Pugh class C and tumor size >5 cm at diagnosis (p Conclusions: Treatment with LDT or liver resection correlated with greater overall survival in this predominantly nonviral cohort of HCC patients. Post-treatment ALBI grade correlated with overall survival and may have prognostic value in guiding clinical management. Mode of initial treatment was a predictor of overall survival, but further studies are needed to compare tumor characteristics between groups. Research is ongoing to evaluate the relationship between chronic liver disease etiology and survival among HCC patients treated with LDT, immunotherapy or a combination of both. Citation Format: Michelle Hartzell, Gary Monroe, Jon Shakesprere, Sijin Wen, J. Wallis Marsh, Jacob Fuqua, Robert Grammer, Beau Toskich, Midhun Malla. Prognostic indicators and outcomes of hepatocellular carcinoma (HCC) in an Appalachian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6745.

This review provides a high level overview of several applications of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) patients. ctDNA has been shown to be a promising prognostic biomarker for detection of minimal residual disease, monitoring for early recurrence and response monitoring in metastatic disease. Prospective studies are ongoing to investigate the ability of ctDNA to inform clinical decision making. This article also reviews existing and emerging alterations in CRC and their respective therapeutic approaches.

5 Background: A growing body of evidence supports the utility of circulating tumor DNA (ctDNA) as a useful biomarker for detecting molecular residual disease (MRD) in colorectal cancer (CRC). Immediately after surgery or during adjuvant therapy, high levels of cell-free DNA (cfDNA) from normal tissue may limit the detection of tumor-derived ctDNA. The optimal timing of blood collection for reliable MRD detection after surgery or adjuvant therapy remains unclear. Methods: In this retrospective, U.S.-based, multi-institutional study, data from commercial ctDNA testing in 16,347 patients with stage I-III CRC were analyzed. Complete clinical data were available for 417 patients with 2,538 plasma samples collected between 6/2019 and 4/2022. The median follow-up for relapsed and non-relapsed patients was 730 and 615 days, respectively. A personalized, tumor-informed multiplex PCR-based next-generation sequencing assay (Signatera) was used to quantify ctDNA prior to surgery and postoperatively in a longitudinal manner. We analyzed the kinetics of total cfDNA and compared it with the ctDNA MRD positivity rates at various time points after surgery. Results: Among all patients, cfDNA levels were higher immediately after surgery (0-2 weeks) and gradually declined during the subsequent 2-8 weeks (p6 months post-operatively and subsequent to any adjuvant therapy) was significantly associated with worse recurrence-free survival as compared to ctDNA negative patients (MRD: HR 14.1, 95% CI: 5.8-34; p

797 Background: UGT1A1 gene polymorphisms are heterogeneously distributed among ethnicities and varying geographical regions. Patients with UGT1A1*6 and UGT1A1*28 polymorphisms have an increased risk of grade 3-4 neutropenia and diarrhea from irinotecan due to poor metabolism. This study evaluated the prevalence of UGT1A1 polymorphisms in the cancer patients in a large tertiary cancer center in the Appalachian region, in order to develop individualized institutional guidelines on the utility of UGT1A1 testing in chemotherapy dose management. Methods: This retrospective study evaluated all patients with gastrointestinal (GI) malignancies who underwent UGT1A1 testing prior to chemotherapy initiation between 1/1/2020 and 6/30/2022 at West Virginia University. All patients within this disease sub-specialty who were eligible for chemotherapy were tested for UGT1A1 *6 and UTG1A1*28 polymorphism via PCR based pharmacogenomic evaluation using OneOme RightMed comprehensive testing. Patients were excluded if they were tested for genetic alterations specifically due to previous treatment intolerances. Prevalence of the alterations along with demographic characteristics of patients are reported. Results: UGT1A1 genotyping was performed in 278 patients prior to initiating chemotherapy and 12 patients were excluded due to insufficient sample. A total of 266 patients met the inclusion criteria. The median age was 66 years (IQR: 26-92). Males constituted a higher proportion of the population compared to females (M: F = 147: 119). Colon (n-81; 30.5%) and pancreatic (n-80; 30%) cancers were the predominant GI malignancies. Fifty five percentage of patients (n-146) had metastatic disease. The distribution of the UGT1A1 variant genotype is showed in the table below. Conclusions: The prevalence of heterozygous and homozygous of UGT1A1*28 polymorphism in GI cancer patients in the Appalachian region is 51.5%, consistent with the reported literature. Homozygous and heterozygous UGT1A1 *28 alterations constituted 13.2 and 38.3% respectively. Data collection for pre-emptive chemotherapy dosage adjustments and adverse events is ongoing to integrate testing for UGT1A1 polymorphism routinely for all GI malignancies cancer patients starting irinotecan chemotherapy.[Table: see text]

245 Background: Mesothelin (MSLN) is highly expressed in several malignancies including colorectal cancer (CRC) compared to normal tissue and is associated with tumor cell proliferation and worse patient survival. MSLN could be a potential target for antigen-specific therapy. Here, we characterized the MSLN expression in CRC and its association with molecular and immune-related markers. Methods: 15,673 CRC samples were tested by NGS (592, NextSeq; WES, NovaSeq), WTS (NovaSeq) (Caris Life Sciences, Phoenix, AZ). Microsatellite-instability (MSI) was tested by fragment analysis, IHC, and NGS. Tumor mutational burden (TMB) totaled somatic mutations per tumor (high>10 mt/MB). Tumors with MSLN-high(H) and MSLN-low(L) expression were classified by top and bottom quartile, respectively. Real world overall survival (OS) was extracted from insurance claims and calculated using Kaplan-Meier estimates for molecularly defined cohorts from tissue collection to last contact. Statistical significance was determined using chi-square and Mann-Whitney U test with p-values adjusted for multiple comparisons (q

OPINION STATEMENT Data supporting the use of immunotherapy in the treatment of gastroesophageal cancer continues to evolve. The promising results from adjuvant immunotherapy and trials combining immunotherapy plus chemotherapy in the 1L setting have led to broad US FDA approvals. Among the PD-L1 negative subgroups, the magnitude of benefit is diminished; effective therapy for this population remains an unmet need. A detailed biologic understanding of the PD-L1 negative (and low) population represents a barrier to developing effective combination therapies, although combination angiogenesis inhibitors and immunotherapy look encouraging. Early phase clinical trials, particularly with pembrolizumab plus lenvatinib (EPOC 1706), demonstrated a clear signal independent of PD-L1, and a confirmatory phase III trial of pembrolizumab plus lenvatinib is planned. Conceptually, it is important to think of immune checkpoint inhibitor therapy as targeted therapy, most active in clearly defined biomarker-selected populations. Pre-planned analyses have reliably shown a clear trend toward a greater magnitude of benefit in patients with higher PD-L1 expression, particularly CPS ≥ 5 and ≥ 10. Whether there is a linear relationship at higher cutoffs is not well known, though it likely represents smaller and smaller populations. Although beyond the scope of this clinically oriented review, recognition of the spatial and temporal heterogeneity in PD-L1 expression is important and repeat testing from progression samples across lines of therapy should be considered. Questions about additional predictive biomarkers, particularly plasma-derived, remain. Responses by tumor histology and location also differ, and special attention to these factors as well as MSI-H, HER2, and EBV subgroups in future trials is warranted. Questions regarding the incorporation of immunotherapy after progression on 1L immunotherapy plus chemotherapy combinations will arise as these combinations are used more frequently, and this represents a key area of future investigation. Overall, the role of immunotherapy continues to expand in GEA, and we welcome any additional tools for this difficult-to-treat group of cancers.

We present a case of a 58-year-old female who presented initially to an outside institution with abdominal pain and was diagnosed on liver biopsy with a well-differentiated neuroendocrine tumor of an unknown primary source. She was referred to our academic institution for a second opinion after disease progression on the initial chemotherapy regimen. Through additional evaluation, diagnostics, and multi-disciplinary tumor board discussion she was diagnosed with metastases from a well-differentiated neuroendocrine neoplasm of the breast (NENB). Consequently, her treatment plan was modified leading to significant clinical and radiological improvement.

Background: Ibrutinib is a Bruton’s tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown. Objective: This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD. Methods: A single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. Results: Patients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06–3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. Conclusions: Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

PURPOSE OF REVIEW: Cancer and heart disease are the leading causes of mortality in the USA. Advances in cancer therapies, namely, the development and use of chemotherapeutic agents alone or in combination, are becoming increasingly prevalent. RECENT FINDINGS: Many chemotherapeutic agents have been associated with adverse cardiovascular manifestations. The mechanisms of these sequelae remain incompletely understood. In particular, microtubule inhibitor (MTI) agents have been related to the development of heart failure, myocardial ischemia, and conduction abnormalities. At present, there are no guidelines for patients undergoing MTI therapy as it pertains to both preventative and mitigatory strategies for cardiovascular complications. We conducted a literature review focusing on content related to the use of MTIs and their effect on the cardiovascular system. SUMMARY: MTIs have been associated with various forms of cardiotoxicity, and fatal cardiotoxicities are rare. The most well-described cardiotoxicities are brady- and tachyarrhythmias. The co-administration of anthracycline-based agents with MTIs can increase the risk of cardiotoxicity.

Introduction: National-level data of cancer patients’ readmissions after a ST-segment elevation myocardial infarction (STEMI) are lacking. Objectives: The primary aim of this study was to describe rates and causes of 30-day readmissions in this population. Methods: Among patients who were admitted with STEMI in the United States National Readmission Database (NRD) from October 2015-December 2017, we identified patients with the diagnosis of active breast, colorectal, lung or prostate cancer. The primary endpoint was 30-day unplanned readmission rate. Secondary endpoints included in-hospital outcomes during the index admission and causes of readmissions. A propensity score model was used to compare the outcomes of cancer and no cancer patients. Results: A total of 385,522 patients were included in the current analysis (Cancer= 5,956, No Cancer=379,566). After propensity score matching, 23,880 patients were compared (Cancer=5,949, No Cancer=17,931). Cancer patients had higher 30-day readmission (19% vs 14%, p Conclusions: About one in five cancer patients presenting with STEMI will be readmitted within 30 days. Cancer patients’ 30-day readmissions are still predominantly cardiac-related but with a higher proportion of admissions for infectious, cancer-related and bleeding and than those without cancer.

517 Background: Pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death, with a recurrence rate of 85% after curative surgery and a 5-year survival rate of 10%. Serum biomarkers like CA 19-9 lack sensitivity and specificity (10% of patients fail to produce CA 19-9), and are poor indicators of molecular residual disease (MRD). Circulating tumor DNA (ctDNA) detection allows for MRD identification months ahead of radiological findings, and may assess molecular response and patient outcomes. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA in a prospective clinical cohort of patients. Serial time points were collected for unresectable, borderline resectable, and resectable subsets of patients to monitor ctDNA levels in response to treatment (see Table). Results: 93 patients were included, with a median age of 67.3 yrs and 45% female. 285 timepoints were analyzed for ctDNA presence, with each patient having between 1 and 7 timepoints (median 3 timepoints per patient). 46 patients had one or more samples positive for ctDNA, resulting in an anytime ctDNA positivity rate of 49.5%. Anytime positivity correlated with the stage of disease (p

4103 Background: Hepatocellular carcinoma (HCC) and biliary tract cancers [BTC - including cholangiocarcinoma (CCA) and gall bladder cancers (GBC)] represent a heterogeneous group of diseases. Glycoprotein-based tumor markers like alpha-fetoprotein (AFP) or carbohydrate antigen 19-9 (CA-19-9) though part of standard-of-care (SOC), lack sensitivity, and specificity. A fair proportion of these cancers do not produce these glycoproteins. Circulating tumor DNA (ctDNA) testing can fill this void and be used for the assessment of molecular residual disease (MRD), as well as for surveillance purposes in patients with HCC or BTC. Prospective evaluation of this methodology in clinical practice has been limited to date. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA. Serial time points were collected on a subset of patients to monitor their ctDNA levels in response to treatment. Results: Here we analyzed 200 plasma samples from a total of 90 patients with HCC (n=27) and BTC (n=63), comprising 46 patients with CCA and 17 patients with GBC. Sample-level ctDNA positivity rates, determined using a tumor-informed assay are presented in table. ctDNA detection was significantly associated with the stage of disease (Wilcoxon rank-sum test, p

tudy Objective To describe three cases of pericarditis probably related to azacitidine administration in a span of 3 years at our center. Design Case series. Setting Comprehensive cancer center within a large, academic medical center. Patients Three patients with high-grade myelodysplastic syndrome or acute myeloid leukemia who received azacitidine. Intervention None. Measurements None. Main Results Patient 1 presented with pericarditis after cycle 2 of azacitidine, patient 3 presented 3 weeks after completing cycle 5, and patient 2 presented during cycle 1. All patients were treated symptomatically and responded to corticosteroids. None of the patients were re-challenged with hypomethylating agents. Use of the Naranjo adverse drug reaction probability scale indicated a probable adverse drug reaction (score of 6) for patients 1 and 3 and a possible adverse drug reaction (score of 3) for patient 2. Conclusion With the exclusion of other common causes of pericarditis, we believe it is likely that azacitidine was responsible for the findings in our patients. Providers caring for patients receiving hypomethylating agents should consider this potential adverse drug reaction in the setting of unexplained chest pain or other clinical signs consistent with cardiotoxicity.

e16076 Background: Median overall survival (mOS) of patients (pt) with metastatic colorectal cancer (mCRC) has improved steadily over the past two decades. However, epidemiological data suggest that cancer outcomes for rural compared to urban dwelling pts are worse. In this study, we retrospectively compared progression free survival (PFS) and OS among mCRC pts residing in urban versus rural areas enrolled in N9741 (1997-2004) and CALGB 80405 (2005-2012) clinical trials. Methods: Zip code data from the Centers for Disease Control (CDC) were used to classify pts into rural or urban dwellers. Chi-square and Kruskal Wallis analyses were used to compare the groups. Survival outcomes were evaluated using Kaplan-Meier estimates, compared by stratified log rank and cox proportional hazards models. Results: In N9741 and 80405 respectively, 217 (35%) and 521 (21%) pts resided in rural areas. Median age of mCRC pts at diagnosis was 60.5 yrs. (rural) compared to 58.6 yrs. (urban) in 80405 (P < 0.01) and 59.6 yrs. to 60.2 yrs. in N9741 (P = 0.4). In 80405, pts in rural areas were less likely to be female (35% vs 43%, P < 0.01) black (6.6% vs 15.1%, P < 0.01), unmarried (51% vs 62%, P < 0.01), and to have private insurance (PI) (45% vs 50%, P = 0.03) when compared to pts in urban areas. In N9741, gender (P = 0.8) and PI (P = 0.3) distribution was similar; pts in rural areas were less likely to be black (1.4% vs 9.1%, P < 0.01). Rural vs urban pt PFS was no different in either trial. MOS was worse in pts in rural areas when compared to urban dwellers in 80405 (Table). OS outcomes stratified based on the use of cetuximab based regimen in 80405 showed worse outcomes for pts in rural compared to urban dwellers (21.9 vs 26.3 mo. HR: 1.22 (1.03-1.44), P = 0.02). Conclusions: MCRC pts from rural areas had a significantly worse mOS when compared to pts in urban areas in 80405. Furthermore, mOS with cetuximab based regimens was 4.4 months shorter in rural pts. The observed rural vs urban dweller mOS disparities in 80405 pts justifies additional research searching for causal factors and the necessity to identify actionable approaches in order to improve pt outcomes in rural areas. Support: U10CA180821, U10CA180882, U10CA180888, UG1CA180830; Pfizer, Sanofi, BMS, Genentech, https://acknowledgments.alliancefound.org . ClinicalTrials.gov Identifier: NCT00003594, NCT00265850. [Table: see text]

176 Background: CRC patients with PM have a significantly worse median overall survival (OS) when compared to those with liver and lung metastases. We studied MSLN protein expression using immunohistochemistry (IHC) on primary resected CRC (PRC), its correlation with future development of PM and its effect on OS. Our hypothesis is that PRC tumors from patients who later developed PM will have an increased proportion of positive MSLN scores based on IHC. Methods: We performed a retrospective case control study of all localized CRC (Stage I, II, III) patients who underwent curative resection from 2000- 2017 at the University of Oklahoma. The target population consisted of PRC patients who had distant recurrence during surveillance. Control group comprised of patients who never recurred after a minimum of 5 years of surveillance. MSLN score was calculated by the sum of staining percentage and intensity scores on each MSLN stained slide. Kaplan-Meier method was used to estimate OS and differences in survival were estimated using log-rank test. Results: Among 100 patients with recurrent CRC, 19 patients had PM, 51 had solid organ only metastases (SOM) and 66 are in the control group. MSLN staining results by IHC were satisfactory in 87 patients (Table). 91%, 46% and 21% of the patients in PM, SOM, and control groups had a positive MSLN score on PRC respectively. A significant association between MSLN score and future development of PM was observed (p [Table: see text]

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is a rare microvascular occlusive disorder characterized by systemic intravascular aggregation of platelets, thrombocytopenia, and mechanical injury to red blood cells. We report a rare case of pernicious anemia presenting as TTP in a Jehovah's Witness. CASE REPORT A 46-year-old Jehovah's Witness female presented with epigastric pain, vomiting, and diarrhea for 2 days and fatigue and paresthesias for 4 weeks. Initial laboratory evaluation showed severe anemia and thrombocytopenia with elevated total bilirubin and lactate dehydrogenase. Peripheral blood smear showed schistocytes, macroovalocytes, and hypersegmented neutrophils. TTP was suspected and plasmapheresis was offered. The patient refused it due to her religious beliefs. Due to the presence of macroovalocytes and hypersegmented neutrophils, vitamin B12 level was checked and found to be extremely low. Anti-intrinsic factor antibodies and anti-parietal cell antibodies were also positive; hence a diagnosis of pernicious anemia was established. Treatment with intramuscular vitamin B12 was initiated, which resulted in dramatic neurologic and hematologic improvement. DISCUSSION Vitamin B12 deficiency can lead to elevated levels of homocysteine in the blood. Homocysteine can cause endothelial dysfunction, which can lead to formation of microvascular thrombi. Due to this phenomenon, vitamin B12 deficiency can rarely present with schistocytes and thrombocytopenia, which combined with other stigmata of vitamin B12 deficiency, can be misdiagnosed as TTP.

Objective: Leptomeningeal carcinomatosis (LMS) is defined as the diffuse infiltration of the leptomeninges and subarachnoid space by malignant cells metastasizing from systemic cancer. Patients usually have a known underlying malignancy, but primary presentation can be with symptoms of meningeal involvement. We describe a rare case of Krukenberg tumor with LMS initially presented as bilateral progressive sensorineural hearing loss, which was misdiagnosed as acoustic neuroma. Patient: A 50 year old man with a history of cervical cancer was referred to the Ear Nose and Throat (ENT) clinic because of progressive hearing loss, tinnitus, dizziness and blurred vision for 5 months. Results: A CT scan of the abdomen and pelvis showed a right adnexal mass, suspicious for an ovarian neoplasm. The patient underwent surgical resection of her pelvic mass. Surgical pathology revealed poorly differentiated adenocarcinoma with scattered signet ring cells, favorable with metastatic gastric adenocarcinoma. Magnetic resonance imaging revealed abnormal leptomeningeal enhancement. A lumbar puncture was performed, the CSF analysis showed elevated protein and positive for signet malignant cells. Conclusion: Our case highlights the importance of the development of new diagnostic tools and treatment regimens for LMC.

e22519 Background: RCS are rare soft tissue sarcomas and account for 0.8-2.7% of malignant kidney tumors. Level 1 evidence guiding optimal patient management is lacking due to the rarity of this disease. Utilizing the NCDB, we analyzed prognostic factors, the current treatment patterns and outcomes in patients with RCS in the United States. Methods: The NCDB was queried from 2004- 2015 for patients diagnosed with MRCS. Baseline patient characteristics were summarized using descriptive statistics. Impact of baseline demographic, Clinicopathologic variables and treatment on overall survival (OS) was evaluated using univariate (UV) and multivariable (MV) cox proportional hazards analysis. Results: 454 patients diagnosed with MRCS between 2004- 2015 were included in this analysis. Median age at diagnosis was 63. Males (62%) had higher incidence of RCS compared with females. 86% (n = 389) were Caucasian, while only 9.5% (n = 43) were African American. Right and left kidneys were equally affected. Spindle cell sarcoma was the most common histology (n = 276). 37.5% (n = 170) underwent CN. 49% of patients received chemotherapy (n = 216) and 24% received radiation therapy (n = 109). Overall, 48% (n = 82) of patients who underwent nephrectomy had chemotherapy. Median OS was 4.5 months (3.8-5.2 mos.). On UV analysis age ≥ 55 years (HR: 1.92, p < 0.001), no systemic treatment (HR: 1.91, P < 0.01), and no CN (HR: 2.1, p < .001) had worse OS. On MV analysis, patients who did not undergo CN had significantly worsened OS compared to CN (7.56 vs 3.35 mos., HR-1.91, CI: 1.52- 2.41 p < 0.001). Patients who received chemotherapy after CN had a better OS (13.3 vs 3.7 mos., p < 0.001). Conclusions: MRCS is an aggressive malignancy with a median OS of less than 5 months. Age at diagnosis, CN and systemic therapy had a statistically significant impact on OS. Given the rarity of the tumor and inadequacy of guidelines, these results can be considered in making management decisions. We understand the limitations of a registry-based study and hence, prospective multi-national clinical trials are essential to further guide us on management of this rare tumor. [Table: see text]

559 Background: RLS is an extremely rare neoplasm with only few case reports documented in the literature. Due to the rarity of this disease, level 1 evidence guiding optimal patient management is lacking. Utilizing the NCDB, we analyzed the current treatment patterns and outcomes in patients with RLS in the United States. Methods: The NCDB was queried from 2004- 2015 for patients diagnosed with T1-4N0-1M0 RLS. Baseline patient characteristics were summarized using descriptive statistics. Impact of baseline demographic, clinicopathologic variables and treatment on overall survival (OS) was evaluated using univariate (UV) and multivariable (MV) cox proportional hazards analysis. Results: 136 patients diagnosed with non-metastatic RLS between 2004- 2015 were included in this analysis. Median age at diagnosis was 64.7 years. Males and females had equal preponderance (50% each). 89% (n = 121) were Caucasian, while only 6% were African American. T staging was based on AJCC 8th edition. 20% of patients had T1 disease, 17% had T2, while T3 and T4 stage was present in 26% and 37% of cases respectively. Only 7% (n = 10) had lymph node (LN) involvement. Dedifferentiated RLS was the most common histology (44%). 59% (n = 80) had radical nephrectomy, 12% (n = 17) had partial nephrectomy, and 17% had nephrectomy NOS. Adjuvant radiation and chemotherapy were used in 15% (n = 20) and 3.6% (n = 5) of patients respectively. Median OS was 41 months (20-76 mos). On UV analysis age ≤ 70 years and sex had a statistically significant effect on OS (HR: 0.387 and 0.549, p < 0.001 and 0.04 respectively). On MV analysis adjusting for age and sex, female patients had a significantly improved OS compared to males (47 vs 36.7mos, HR-0.45, CI: 0.250-0.804 p < 0.05). Conclusions: RLS is a rare and aggressive malignancy with poor outcomes even at localized stage. Age at diagnosis and sex had a statistically significant impact on OS. Given the lack of prospective data, our study provides insights into the prognosis of this rare disease. Additional studies are needed to better guide the optimal management of this rare disease.

Primary adult bladder sarcoma and sarcomatoid carcinoma (formerly carcinosarcoma) are both rare types of malignancy occurring in the urinary bladder. Bladder sarcoma fits into the broad category of soft tissue sarcoma, a term used to describe a heterogeneous group of malignancies derived from cells of mesenchymal origin. Sarcomatoid carcinoma of the bladder is a group of rare biphasic tumors that contains an epithelial component adjacent to a mesenchymal component. Although these tumors are widely considered to have a poor prognosis, the body of literature is limited to case reports and small, single institutional series. Because of their rarity, there is no consensus on the optimal management of these tumors. In this review, we aim to provide an overview of the epidemiology, clinical features, treatment, and prognostic significance of primary adult sarcoma and sarcomatoid tumors of the urinary bladder.

e24058Background: We aim to investigate role of circulating tumor cells (CTC) as supplementary marker to imaging to predict response to therapy in non-small cell lung cancer (NSCLC) patients (pt). ...

Thrombotic thrombocytopenic purpura (TTP) is a rare microvascular occlusive disorder characterized by systemic intravascular aggregation of platelets, thrombocytopenia, and mechanical injury to red blood cells. We report a rare case of pernicious anemia presenting as TTP in a Jehovah's Witness.A 46-year-old Jehovah's Witness female presented with epigastric pain, vomiting, and diarrhea for 2 days and fatigue and paresthesias for 4 weeks. Initial laboratory evaluation showed severe anemia and thrombocytopenia with elevated total bilirubin and lactate dehydrogenase. Peripheral blood smear showed schistocytes, macroovalocytes, and hypersegmented neutrophils. TTP was suspected and plasmapheresis was offered. The patient refused it due to her religious beliefs. Due to the presence of macroovalocytes and hypersegmented neutrophils, vitamin B12 level was checked and found to be extremely low. Anti-intrinsic factor antibodies and anti-parietal cell antibodies were also positive; hence a diagnosis of pernicious anemia was established. Treatment with intramuscular vitamin B12 was initiated, which resulted in dramatic neurologic and hematologic improvement.Vitamin B12 deficiency can lead to elevated levels of homocysteine in the blood. Homocysteine can cause endothelial dysfunction, which can lead to formation of microvascular thrombi. Due to this phenomenon, vitamin B12 deficiency can rarely present with schistocytes and thrombocytopenia, which combined with other stigmata of vitamin B12 deficiency, can be misdiagnosed as TTP.

e15532 Background: Sarcomatoid bladder carcinoma (SRBC) is a rare variant of urothelial cancer. Current data is limited on clinical features, appropriate management and outcomes. Methods: A retrosp...