A Tale of Two NETs: A Pheochromocytoma Masquerading as a Pancreatic NET

Introduction: Neuroendocrine tumors (NETs) are rare endocrine neoplasms with myriad of clinical manifestations. We present a case of two different NETs in a patient to increase physician awareness and highlight the importance of prompt multidisciplinary approach to avoid catastrophic complications. Case Presentation: A 58-year-old female with history of hypertension, diabetes mellitus and gastroesophageal reflux was referred to an oncology office for systemic therapy regarding suspected metastatic pancreatic neuroendocrine tumor based on abdominal imaging demonstrating a 1.6 cm pancreatic lesion and a 1.2 cm hypervascular right adrenal nodule. Endoscopic ultrasound with fine needle aspiration/biopsy of the pancreatic lesion was consistent with well differentiated NET WHO grade 1. Ga-68 Dotetate scan showed focal radiotracer uptake in the pancreatic tail and the right adrenal gland compatible with metastatic disease. The patient endorsed flushing, headache, gastroesophageal reflux and cough in addition to recent worsening in glycemic control, but denied any diarrhea or rashes. Vital signs were notable for elevated blood pressure to 188/90 mm of Hg. Physical exam was unremarkable. Further investigations revealed Chromogranin A 205 ng/ml, Plasma free metanephrines 552 pg/ml, a.m. cortisol 1 ug/dl following dexamethasone suppression test. Non-suppressibility in plasma free metanephrines was demonstrated with clonidine suppression test, concerning for pheochromocytoma. Multidisciplinary approach was initiated, she was placed on Doxazosin with improvement in her blood pressure. Staged surgical resection of pheochromocytoma followed by pancreatic NET management is currently planned. Discussion: Pancreatic NETs, also known as islet cell tumors, arise in the endocrine tissues of the pancreas and may be non-functional or secrete a variety of hormones including insulin, glucagon, gastrin and vasoactive intestinal peptide. In general, these are rare neoplasms, representing one to two percent of all pancreatic tumors (Manuel-Vasquez et al., 2018). Most commonly pancreatic NETs arise sporadically, however they can be associated with genetic syndromes including multiple endocrine neoplasia type I (MEN1), von Hippel-Lindau syndrome, neurofibromatosis type I or tuberous sclerosis (Metz & Jensen, 2008). Pancreatic neuroendocrine tumors may be associated with pheochromocytomas as seen in the patient represented in our report as in patients with the above-mentioned genetic predispositions. Pheochromocytomas are rare catecholamine secreting tumor with malignant potential that arises from chromaffin cells of the adrenal medulla. The most common clinical sign of pheochromocytoma is sustained hypertension, occasionally accompanied by excessive sweating, headache & heart palpitations (Pacak et al., 2001). However, pheochromocytomas are incredible rare with the incidence being cited as 0.8 per 100,000 person years in one study (Beard et al., 1983). Biochemical confirmation of the diagnosis using total fractionated urine metadrenalines or plasma-free metadrenalines should be followed by radiological evaluation to locate the tumor (Davison et al., 2017). Treatment of pheochromocytomas involves resection of the pheochromocytoma following appropriate medical preparation with alpha-adrenoreceptor blockade, calcium channel antagonists or alpha-metyrosine (Naranjo et al., 2017). Prompt diagnosis and proper multidisciplinary management is important to avoid delay in management and potential catastrophic cardiovascular and neurologic complications. To our knowledge this is the first reported case of a pancreatic NET and pheochromocytoma in an adult patient. Discovering two different NETs dramatically changed treatment strategy and offered hope for curative resection.https://scholarlycommons.henryford.com/merf2020caserpt/1073/thumbnail.jp

Acute MI After First Sipuleucel-T Infusion for Prostate Cancer

Introduction: Advances in cancer therapy have improved patient survival statistics; however, treatment related adverse events can lead to significant morbidity and may be life threatening. Sipuleucel-T is the first FDA approved therapeutic cancer vaccine based on improved overall survival in patients with metastatic castration resistant prostate cancer. We describe a case of acute ST segment elevation myocardial infarction (STEMI) in a patient during the first sipuleucel-T infusion. Our aim is to increase physician awareness of this potential complication in order to avoid catastrophic outcome. Case presentation: A 59 year old gentleman with metastatic castration resistant prostate cancer, hypertension, diabetes and no prior cardiac disease (normal pharmacologic stress test and CT coronography within the last year) was undergoing his first sipuleucel-T infusion when he developed sudden chills. No signs or symptoms of anaphylaxis were reported. Patient’s presentation was attributed to infusion reaction. Diphenhydramine 50 mg was given with resolution of the symptoms. Within 20 minutes he developed substernal chest tightness with left arm radiation, along with dyspnea and diaphoresis. Vital signs were notable for BP 90/40, HR 94, and oxygen saturation 96% on room air. Physical exam revealed a diaphoretic male, with normal cardiac, chest, abdominal and extremity examination. EKG showed ST elevation in III, AVF with reciprocal depressions in anterolateral leads. Emergent left heart catheterization (LHC) revealed the culprit lesion at mid RCA (99% obstruction) and a Synergy drug-eluting stent (DES) was placed. In the recovery room, the patient had recurrent chest pain. Repeat emergent LHC revealed acute in-stent thrombus and likely plaque protrusion in the proximal end of previously placed stent with distal embolization. The lesion was ballooned requiring additional DES placement proximally overlying the initial stent and ultimate intraaortic balloon pump for coronary perfusion. He was discharged home in satisfactory condition with appropriate goal directed therapy. Discussion: Sipuleucel-T is an active cellular immunotherapy consisting of autologous peripheral-blood mononuclear cells that have been activated ex vivo with a recombinant fusion protein (PA2024). It has shown to improve survival in a phase III trial. Despite its approval over a decade ago, there remains a paucity of literature describing safety data in the post-marketing period. Summary of US reports submitted to FAERS (surveillance system designed to report AEs associated with drugs) revealed 38 cases of myocardial infarctions, all of which occurred after 2nd or 3rd doses. Most patients had cardiac risk factors. To our knowledge, this is the first case report describing STEMI in a patient during the first sipuleucel-T infusion. Increased awareness of this potential adverse event is important for involved physicians to avoid significant morbidity and mortality of affected patients.https://scholarlycommons.henryford.com/merf2020caserpt/1018/thumbnail.jp

A Case of Chronic Eosinophilic Leukemia in a Patient With Recurrent Cough, Dyspnea, and Eosinophilia

We report the case of a 40-year-old man with no significant past medical history who had been hospitalized multiple times over the course of one year with recurring cough, dyspnea, pruritic rash, and variable degrees of eosinophilia. He was variably diagnosed with asthma and pneumonia. After his last hospitalization with severe symptoms, the patient was referred for pulmonary evaluation where hypereosinophilia (HE) led to a hematologic workup. Fluorescence in situ hybridization revealed the FIP1L1-PDGFRA gene fusion and bone marrow analysis confirmed a diagnosis of chronic eosinophilic leukemia. The patient was treated with daily imatinib and prednisone and he was symptom-free at a four-week follow-up examination

The Effects of Drug User Registration Laws on People's Rights and Health: Key Findings From Russia, Georgia, and Ukraine

Synthesizes research on how drug user registration leads to unfair restrictions on users' human rights and access to drug treatment. Recommends educating law enforcement and others on regulations, prosecuting rights violations, and system reform

1317P Renal toxicity in black patients with non-squamous non-small cell lung cancer treated with combination platinum-pemetrexed-pembrolizumab therapy

Background: In Keynote 189, an increased incidence of renal toxicity was observed with combination platinum-pemetrexed-pembrolizumab (PPP) therapy compared to chemotherapy alone. Studies have shown that compared to White Americans, Black Americans are at higher risk of morbidity and mortality associated with chronic kidney disease (CKD). We conducted a retrospective analysis of patients treated with PPP to assess the rate of renal toxicity in Black and White patients. Methods: Data of self-identified non-hispanic (NH) Black and NH White patients with advanced NS-NSCLC who were treated with PPP between January 1, 2017, and November 1, 2020, at the Henry Ford Health System was analyzed. Serum creatinine (Cr) and calculated glomerular filtration rate (GFR) before the first cycle of PPP and over the duration of PPP therapy were assessed. Acute kidney injury (AKI) was defined as an increase in Cr 1.5 times the baseline value. Reduction in GFR of ≥ 30% was considered significant. Multiple variables and outcomes were analyzed by two-group comparisons, univariate analysis, and Cox regression. Results: A total of 134 patients were included in the analysis. The mean age was 66.5 (SD 8.6) years, and 65 (48.5%) patients were men. A total of 33 (24%) patients were NH Black and 101 (75.4%) were NH White. There were 10 (8.1%) patients who developed AKI, and the median time to development of AKI was 4.5 months. No significant association of Black (3) or White (7) ethnicity with AKI was observed (p =.57). The odds of developing AKI was not increased in patients with a history of hypertension (p =.67), diabetes mellitus (p =.33), cardiovascular disease (p =.68), or CKD (p =.33). A total of 17 out of 127 (13.4%) patients had significantly reduced GFR, and patients with CKD were more likely to have reduced GFR (OR 4.8, p =.02). At the median follow-up of 24.5 months, the median survival was 15.2 months (95% CI, 12.7-22.2). Black ethnicity (HR 1.21, p =.46) and development of AKI (HR 1.13; 95% CI, 0.45–2.86) were not associated with increased mortality. Conclusions: Black patients with NS-NSCLC treated with PPP are not at higher risk of AKI or death than White patients. Development of AKI after PPP therapy was not associated with increased mortality

Impact of COVID-19 Infection on 24 Patients with Sickle Cell Disease One Center Urban Experience, Detroit, MI, USA

The city of Detroit has a large population of individuals with sickle cell disease, and hospitals in Detroit have seen some of the highest numbers of cases of coronavirus disease-19 (COVID-19) in 2020. The purpose of this study was to examine the pathophysiological characteristics of COVID-19 in patients with sickle cell disease or trait to determine whether these patients have unique manifestations that might require special consideration. This retrospective analysis included 24 patients with confirmed COVID-19 and sickle cell disease or trait who were seen at the Henry Ford Hospital, Detroit, MI, USA, between March 1 and April 15 2020. Of the 24 patients, 18 (75.0%) had heterozygous sickle cell trait, one (4.0%) was a double heterozygote for Hb S (HBB: c.20A\u3eT)/β(+)-thalassemia (β(+)-thal), four had sickle cell anemia (β(S)/β(S)) and one (4.0%) had Hb S/Hb C (HBB: c.19G\u3eA) disease. A total of 13 (54.0%) patients required hospitalization. All four patients with sickle cell anemia, developed acute pain crisis. We observed one patient who developed acute pulmonary embolism and no patients developed other sickle cell associated complications. Additionally, three (13.0%) patients required packed red blood cell transfusion without the need of exchange transfusion, and one patient required admission to the intensive care unit (ICU), mechanical ventilation and subsequently died. Patients with sickle cell disease or trait and laboratory-confirmed COVID-19 had a generally mild, or unremarkable, course of disease, with lower chances of intubation, ICU admission and death, but with a slightly longer hospitalization

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors

COVID-19 Severity and Cardiovascular Outcomes in SARS-CoV-2-Infected Patients With Cancer and Cardiovascular Disease

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all CONCLUSIONS: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)

Hematology/Oncology Fellowship Emergency Restructuring in Response to the COVID-19 Pandemic—Henry Ford Hospital, Michigan

The COVID-19 pandemic has wreaked havoc and created challenges in various subspecialty training programs, including hematology/oncology fellowship programs. The challenge of social distancing, providing care for those infected by COVID-19, continuing appropriate treatment of time-sensitive diseases, and the looming threat of health care worker infections required swift planning and restructuring of training programs. The Accreditation Council for Graduate Medical Education provided leeway to tackle the challenges faced by institutions and training programs in the setting of the COVID-19 pandemic. Currently, there is no established guideline specific to hematology and oncology fellowship programs. While understanding that there is no one-size-fits-all, shared experiences can assist training programs to incorporate best practices and customize their programs to provide an active educational environment that balances patient care needs, didactics, scholarly activities, and wellbeing during the process of rapid changes and adaptation. We share our hematology/oncology fellowship program\u27s restructuring approach in response to the COVID-19 pandemic

1632P At home androgen deprivation therapy for patients with prostate cancer during the COVID-19 pandemic. One center experience

Background: COVID-19 pandemic created major challenges in cancer care. Studies have shown increased risk for COVID-19 infectivity, severe disease and death in patients with cancer. Cancer centers worldwide adapted by modifying and often delaying treatment to minimize contact with patients. Methods: To provide safe and uninterrupted care for patients, a home care program was created for patients with prostate cancer at Acad. F. Todua Medical center. Men with locally advanced or metastatic prostate cancer (MPC) receiving androgen deprivation therapy (ADT) were enrolled. Patients and their caretakers were instructed on gonadotropin-releasing hormone (GnRH) subcutaneous injections (SQ) for home administration. Monthly at home laboratory testing and virtual consultations with medical oncologists every 1-3 months were arranged. Results: A total of 52 patients were enrolled during the period of March 2020 – March 2021. All men were White and had ECOG 0/1. The mean age was 71 [±6.3 y] years. Sixteen (31%) patients had stage IIIB PC and 36 (69%) patients had stage IV disease. Stage IIIB patients were receiving adjuvant ADT with SQ Goserelin Acetate 10,8mg every 8 weeks and bicalutamide 50mg daily for two weeks after definitive local treatment. Thirty-one (86%) patients had hormone sensitive metastatic PC and were receiving SQ Goserelin Acetate 10.8mg (28) every 8 weeks or SQ Leuprolide Acetate 22,5mg every 8 weeks (3) with 2 weeks of Bicalutamide 50mg daily. Five (14%) patients had castration resistant (CR) PC and were receiving SQ Goserelin Acetate 10,8mg every 8 weeks with Enzalutamide 160mg daily. Thirty-three (63%) patients had Gleason’s score of 8/9. All patients were compliant with home injections, laboratory tests and virtual physician visits. Thirty-nine (75%) patients administered injections by themselves. Forty-two (80%) patients had PSA reduction \u3e50%. Ten (20%) patients had disease progression and required clinic visits for investigations. Median time to progression was 12 months. Only 1 (2%) patient acquired COVID-19 infection, was hospitalized and died of respiratory failure. Conclusions: At home ADT with appropriate patient/caregiver education and close follow up may be safe for patients with PC during the COVID-19 pandemic