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Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.

Recognition of the adverse events of inferior vena cava filters (VCFs) has prompted the Food and Drug Administration (FDA) to issue safety warnings (2010 and 2014), advocating for removal, once the risk of pulmonary embolism has abated. Despite an initial increase in retrieval rates, these remain low (25–30% at 1 year in 2014). We retrospectively investigated retrieval trends in adults with VCFs placed between 2015 and 2018 at a single institution. The rate of retrievable VCF removal accounting for the competing risk of death was the main outcome. There were 494 VCFs placed (305 retrievable). The cumulative incidence of retrieval remained low (21% at 1 year), even after the second FDA warning (2014). Patients who resumed anticoagulation (AC) at any time were more likely to have retrieval (hazard ratio [HR] = 3.6, p

Sickle trait (Hb SA) or sickle disease (Hb SS) carries increased risk of venous thromboembolism (VTE). Hb SS patients are young and lack common comorbid conditions that qualify them for VTE prophylaxis (VTEP).Retrospective, multicenter analysis of Hb SS/Hb SA adult patients between January 2013 and December 2018.There were 803 Hb SA (525 patients) and 1020 Hb SS admissions (262 patients). VTEP use was similar between Hb SA and controls (42% vs. 46%; p-value = .06) and Hb SS and controls (45% vs. 42%; p-value = .13). Hb SS/Hb SA patients more frequently received more than half of prescribed doses of VTEP. In multivariate analysis, increasing age and longer hospitalizations were positive predictors. Odds of VTEP use varied with treatment site for Hb SS patients, whereas comorbid conditions, admission hemoglobin and platelet count were not predictive. By contrast, in Hb SA patients, comorbid conditions, higher admission hemoglobin, and higher admission platelet counts raised the odds of VTEP being offered.VTEP is underused in Hb SS/Hb SA patients. There may be a trend toward offering more VTEP in Hb SS disease, but not in Hb SA patients, where VTEP prescribing is driven by comorbid conditions rather than genotype. Patient compliance does not appear to play a major role, but intercenter variability suggests provider education may improve VTEP use.

Abstract: Cardiotoxicity from chemotherapy regimens has been long reported. However, the understanding of cardiac side effects of biological therapies is rapidly evolving. With cancer patients achieving higher life expectancy due to the use of personalized medicine and novel targeted anticancer agents, the occurrence of cardiotoxicity is becoming more significant. Novel biological therapies include anti-HER2 antibodies, tyrosine kinase inhibitors, bruton kinase inhibitors, antivascular endothelial growth factors, proteasome inhibitors, immunomodulator drugs, and immune checkpoint inhibitors. Potential cardiovascular toxicities linked to these anticancer agents include hypertension, arrhythmias, QT prolongation, myocardial ischemia and infarction, left ventricular dysfunction, congestive heart failure, and thromboembolism. Cardiac biomarkers, electrocardiography, echocardiography and magnetic resonance imaging are common diagnostic modalities used for early detection of these complications and timely intervention. This review discusses the various types of cardiotoxicities caused by novel anticancer biologic agents, their molecular and pathophysiological mechanisms, risk factors, and diagnostic and management strategies that can be used to prevent, minimize, and treat them.

Background Hypercoagulability may contribute to COVID‐19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. Objectives We evaluated the impact on survival of different AC doses in COVID‐19 patients. Methods Retrospective, multi‐center cohort study of consecutive COVID‐19 patients hospitalized between March 13 and May 5, 2020. Results A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan‐Meier plot demonstrated different 25‐day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS–weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22‐0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05‐0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. Conclusions Higher doses of AC were associated with lower mortality in hospitalized COVID‐19 patients. Prospective evaluation of efficacy and risk of AC in COVID‐19 is warranted.

Heparin-induced thrombocytopenia (HIT) is a recognized clinical entity in patients receiving unfractionated heparin and low-molecular weight heparin. Currently, diagnosing HIT includes the combination of a physician's clinical suspicion based on a clinical scoring system and a series of laboratory tests. In the present article, we discuss challenges in suspecting and diagnosing HIT in consideration of the turnaround time of available tests and recent advances in techniques and methodologies of newer immunoassays and functional assays.

OBJECTIVES Cancer patients are using medical cannabis (MC) to address symptoms; however, little data exist to guide clinicians when counseling patients. We seek to define the patterns of MC use among cancer patients, as well as efficacy and safety of MC. MATERIALS AND METHODS Cancer patients attending oncology office visits at Beaumont Hospital, Michigan from July to December 2018 were anonymously surveyed. The survey included data regarding demographics, diagnosis, treatment, symptom burden, and MC use. Patients who reported MC use since their cancer diagnosis completed a section on patterns of use, efficacy, and safety. RESULTS The response rate was 188 of 327 (57.5%). MC use was reported by 46 of 188 (24.5%). A median composite baseline symptom score ranging from 8 (best) to 32 (worst) was higher in patients using MC versus nonusers; 17.5 versus 14.4 (P

Objectives: Although life-threatening emergencies for cancer patients are relatively rare, cancer patients often seek care in the emergency department. The use of emergency medical service (EMS) by...

Background: Male breast cancer is rare accounting for less than 0.5% of all cancer diagnoses in men. Previous epidemiological studies reported conflicting results regarding the prognosis of male breast cancer in comparison to female breast cancer. As treatment for breast cancer has improved significantly, we conducted this study to evaluate male breast cancer characteristics and mortality. Methods: All patients diagnosed with breast cancer between 2010 and 2015 from the population-based cancer registries of the Surveillance Epidemiology and End Results program (SEER) were analyzed. Descriptive statistics, Kaplan-Meier analysis and COX regression model were used to examine the data. Results: A total of 380,116 cases of breast cancer were found including 2,978 cases of male breast cancer. The age-adjusted incidence rate for male breast cancer during the study period was 1.2 per 100,000 individuals per year which is slightly higher than the rate during the 10 years period preceding our study date (1.1 per 100,000 per year). Out of all male breast cancer patients, 80.7% of them were white, 14.6% black and 4.7% from other races. The median age of diagnosis was 68. 34% of male breast cancer patients were diagnosed with stage I, 41.6% with stage II, 16.2% with stage III and 8.2% with stage IV. 97% of male breast cancer cases were ER/PR positive and 11.9% were HER2 positive. 5-year survival rate for male breast cancer patients was 90% for stage I, 86% for stage II, 78% for stage III and 28% for stage IV. Cox proportional-hazards model revealed a slight increase in mortality associated with male breast cancer in comparison to female breast cancer (adjusted hazard ratio, 1.15; 95% confidence interval, 1.06 to 1.24; P Conclusions: Male breast cancer represents less than 1% of breast cancer cases. Its age-adjusted incidence rate has slightly increased. It is mostly diagnosed as early stage with positive hormone receptors status. After controlling for other risk factors, male breast cancer patients have a worse survival outcome than female patients. Citation Format: John Khoury, Nwabundo Anusim, David Macari, Ishmael Jaiyesimi. Demographics and survival in male breast cancer: An updated analysis of SEER database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-07.

Background: Inflammatory breast cancer (IBC) is a rare and aggressive malignancy, distinguished by characteristic skin changes with/without breast mass. While new therapies have improved the survival of IBC, the prognosis of metastatic disease (stage IV) remains poorly described. The current analysis is aimed at investigating the demographics of metastatic IBC and the impact of chemotherapy use and tumor subtype on survival. Methods: Using ICD-O-3 histology code 8530/3 in the Surveillance Epidemiology and End Results database (SEER), demographics and survival data on metastatic IBC diagnosed between 2010 and 2015 were abstracted. JMP 14 statistical software was used for data analysis. The SEER database does not record specific age above 85 years and these cases were excluded. Results: Over five years, 378 patients were diagnosed with metastatic IBC. All were women and most were Caucasian (282, 75%). Mean age was 60±14 years. During the observation period 284 (75%) patients died and of which 218 deaths were attributable to IBC. Cancer subtype was unknown in 61 patients; for the rest, Luminal A was the most common (121, 38%), followed by triple negative (74, 23%), HER2 enriched (62, 20%) and luminal B (60, 19%). Median overall survival (OS) was 18 months (95% CI 14-20), with a survival rate of 39% at 24 months from diagnosis. In unadjusted analyses, patients receiving chemotherapy (n=191) had increased survival at every time point compared to those who did not (n=93), (median OS 22 (95% CI 18-26) vs 5 months (95% CI 2-11), p Conclusion: From our data, IBC is common in Caucasian women in their 7th decade of life. Luminal B was the least common cancer subtype and had the best overall survival. Chemotherapy appears to play an important part in increasing survival; but ethnicity and tumor subtype are also important predictors of mortality. Keywords: Inflammatory breast cancer, Metastatic, Survival, Demographics Citation Format: Nwabundo Anusim, Filip Ionescu, John Khoury, Anish Konde, Ishmael Jaiyesimi. Demographics and survival in metastatic inflammatory breast cancer. SEER data analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-15-05.

Nuclear carcinoma of the testis (NUT) midline carcinoma are rare, poorly differentiated tumors resulting from t(15; 19) rearrangement, clinically characterized by aggressive and rapid progression to death. No optimal treatment regimen has been established for this rare malignancy. Surgery, chemotherapy, and radiation have been used for treatment alone or in combination, depending on location and staging of the disease, and may confer short periods of remission; however, re-emergence of the disease inevitably occurs. Targeted therapies such as bromodomain and extra-terminal domain protein (BET) inhibitors are currently in early phases of clinical trials. Here we describe a 49-year-old-male with no comorbidities who presented with acute worsening of chronic cough, new onset hemoptysis and left sided chest pain for 2 weeks. Workup revealed stage IIIB NUT midline carcinoma (NMC) of the lung with next-generation sequencing confirming the presence of a NUTM1-BRD4 fusion. The tumor was unresectable, and he began concurrent chemoradiation with weekly carboplatin and paclitaxel for 5 weeks. The follow-up CT scan showed partial response, so maintenance was continued with durvalumab. Two months later, he presented with metastasis to the posterior muscle compartment of the left arm, which was treated with local radiotherapy. Four months later he developed progression of lung disease with multiple pulmonary nodules. Durvalumab was discontinued and he was prescribed the BET inhibitor molibresib, 120 mg daily. After nearly 3 months of treatment with molibresib, he presented with brain metastasis for which he had a craniotomy with tumor resection and gamma knife radiation to solitary metastatic lesions. He was then prescribed chemo-immunotherapy with carboplatin plus pemetrexed and pembrolizumab. After two cycles of treatment his disease progressed, and he succumbed to it. Total survival was 18 months. In conclusion, NUT midline lung carcinoma is a rare but aggressive malignancy and patients have limited treatment options especially in advanced stages. Few targeted therapies have shown promising results in early clinical trials but more treatment options are awaited.

PURPOSE To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric antigen receptor (CAR) T-cell therapy. METHODS A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021. RESULTS The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell–related toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell–associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell–associated neurotoxicity syndrome should be managed with corticosteroids and supportive care. Additional information is available at www.asco.org/supportive-care-guidelines .

PURPOSE To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitor (ICPi) therapy. METHODS A multidisciplinary panel of medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to update the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 through 2021. RESULTS A total of 175 studies met the eligibility criteria of the systematic review and were pertinent to the development of the recommendations. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS Recommendations for specific organ system–based toxicity diagnosis and management are presented. While management varies according to the organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, except for some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert ≤ grade 1. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids. Corticosteroids should be tapered over the course of at least 4-6 weeks. Some refractory cases may require other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, except for endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines .

Plasma cell leukemia is rare and could be life-threatening. Even rarer and equally life-threatening is cryoglobulinemia. Both of them occurring together paints a grim clinical picture. We present the case of a 63-year-old male with plasma cell leukemia complicated by cryoglobulinemia with skin lesions. The report briefly reviews the clinical and diagnostic characteristics of plasma cell leukemia and well as available treatment options. It also highlights the need to consider non-chemotherapy-based regimens and clinical trials in the care of plasma cell leukemia patients.

The advent of bone marrow transplant has opened doors to a different approach and offered a new treatment modality for various hematopoietic stem-cell-related disorders. Since the first bone marrow transplant in 1957, there has been significant progress in managing patients who undergo bone marrow transplants. Plasma-cell disorders, lymphoproliferative disorders, and myelodysplastic syndrome are the most common indications for hematopoietic stem-cell transplant. Despite the advances, invasive fungal infections remain a significant cause of morbidity and mortality in this high-risk population. The overall incidence of invasive fungal infection in patients with hematopoietic stem-cell transplant is around 4%, but the mortality in patients with allogeneic stem-cell transplant is as high as 13% in one study. Type of stem-cell transplant, conditioning regimen, and development of graft- versus-host disease are some of the risk factors that impact the risk and outcomes in patients with invasive fungal infections. Aspergillus and candida remain the two most common organisms causing invasive fungal infections. Molecular diagnostic methods have replaced some traditional methods due to their simplicity of use and rapid turnaround time. Primary prophylaxis has undoubtedly shown to improve outcomes even though breakthrough infection rates remain high. The directed treatment has seen a significant shift from amphotericin B to itraconazole, voriconazole, and echinocandins, which have shown better efficacy and fewer adverse effects. In this comprehensive review, we aim to detail epidemiology, risk factors, diagnosis, and management, including prophylaxis, empiric and directed management of invasive fungal infections in patients with hematopoietic stem-cell transplant.

Background: There is controversy surrounding the benefit of adjuvant therapy for patients with pT2N0, stage IB gastric adenocarcinoma following surgical resection. Methods: Patients with T2N0 gastric adenocarcinoma (tumor invasion into the muscularis propria) who underwent surgical resection with pathological evaluation of at least 15 lymph nodes were identified from the Surveillance Epidemiology and End Results Registry (SEER) database. Demographics, adjuvant therapy, and survival data were collected and analyzed using SPSS statistical software. Results: A total of 452 cases were identified between 2004 and 2014. Median age at diagnosis was 69. 60.2% of the patients were white, 27.7% Asian, 10.8% black, and 1.3% from other races. Adjuvant therapy was administered to 30.5% of the patients, of which 44.2% received chemoradiation, 48% chemotherapy only, and 7.2% radiation therapy only. After a median follow up of 39 months, the median overall survival (OS) was not reached in the group of patients who received adjuvant therapy versus 100 months in the group that did not receive adjuvant therapy (P=.005). The 5-year OS rate (5-YOS) was 77% for the adjuvant therapy group versus 62% for those who did not receive adjuvant therapy. Univariate analysis revealed that the hazard ratio for death [adjuvant therapy vs observation] was 0.54; 95% CI, 0.35 to 0.83. Adjuvant therapy showed statistically significant survival benefit in patients younger than 60 years of age (5-YOS, 95% vs 79%) and failed to show survival benefit in patients older than 60 (5-YOS, 63% vs 58%). Multivariate analysis revealed that age was associated with mortality, whereas sex, race, grade, tumor size, and number of lymph nodes examined were not associated with increased mortality. Conclusions: Adjuvant therapy provided survival benefit for pT2N0, stage IB resected gastric adenocarcinoma. Our results suggest that patients younger than 60 year of age may benefit the most from this therapy.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. While patients with COVID-19 most frequently present with pneumonia, respiratory failure and acute respiratory distress syndrome, increasing cases of immune-mediated disorders such as autoimmune thrombocytopenia, haemolytic anaemia and antiphospholipid syndrome have been reported. In this article we describe a rare case of cold agglutinin syndrome (CAS) in a patient with COVID-19. The patient was a 77-year-old man with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency who presented with COVID-19 infection and acute respiratory failure. Initially he was started on intravenous steroids, antibiotics and hydroxychloroquine. Laboratory analysis revealed haemolytic anaemia with a positive direct anti-globulin test (DAT) and high titres of cold agglutinins. Hydroxychloroquine was stopped due to suspicion of haemolysis due to G6PD deficiency but the haemolysis persisted. Unfortunately, the respiratory failure progressed and the patient died. In summary, this article describes a rare case of CAS associated with COVID-19. CAS is a heterogenous group of cold autoimmune haemolytic anaemias occurring secondary to infections or malignancies. No definite treatment for CAS in COVID-19 patients has been approved so far. LEARNING POINTS Autoimmune haemolytic anaemia has been reported in COVID-19 patients. Cold agglutinin syndrome (CAS) can occur in patients with COVID-19. Efforts to determine the optimal management of CAS in COVID-19 patients must continue. Keywords: Coronavirus disease 2019, cold agglutinin syndrome, case report, autoimmune hemolytic anemia INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel enveloped RNA betacoronavirus that emerged in December 2019 in Wuhan, China and rapidly spread worldwide [1]. This virus is responsible for causing a multi-system disorder called coronavirus disease 2019 (COVID-19) syndrome. It has now been established that the hyperinflammatory response induced by SARS-CoV-2 causing fulminant and fatal cytokine release is a major cause of disease severity and death in infected patients [2,3]. While hypercoagulability [4], autoimmune cytopenias[5] and anti-phospholipid antibody syndrome[4] have emerged as the most common haematological disorders in COVID-19 patients, 14 cases of autoimmune haemolytic anaemiahave also been reported [6–12]. Individuals with autoimmune haemolytic anaemiaproduce warm, coldor mixed-reactive antibodiesthat are directed against antigens on the surface of red blood cells (RBCs) [13].Cold antibody autoimmune haemolytic anaemias can be further divided into cold agglutinin disease (CAD), which is primarily a low-grade clonal lymphoproliferative disorder, and cold agglutinin syndrome (CAS), which is a rare heterogenous group of cold immune haemolytic anaemias that occur secondary to infection or malignancy [14]. Here, we report a case of acute CAS associated with SARS-CoV-2.

Background: Lung cancer is one of the leading causes of cancer mortality in the US. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced non-small cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations while patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. Aims: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. Materials and methods: Published studies included in Medline (via PubMed) and National Comprehensive Cancer Network Guidelines were reviewed for data gathering. Conclusion: The use of next generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune check point inhibitors (ICI) leading to better survival rates and lesser toxicity.

PURPOSE To provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC) with driver alterations. A guideline update for systemic therapy for patients with stage IV NSCLC without driver alterations was published separately. METHODS The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel updated recommendations based on a systematic review of randomized controlled trials (RCTs) from December 2015 to January 2020 and meeting abstracts from ASCO 2020. RESULTS This guideline update reflects changes in evidence since the previous update. Twenty-seven RCTs, 26 observational studies, and one meta-analysis provide the evidence base (total 54). Outcomes of interest included efficacy and safety. Additional literature suggested by the Expert Panel is discussed. RECOMMENDATIONS All patients with nonsquamous NSCLC should have the results of testing for potentially targetable mutations (alterations) before implementing therapy for advanced lung cancer, regardless of smoking status recommendations, when possible, following other existing high-quality testing guidelines. Most patients should receive targeted therapy for these alterations: Targeted therapies against ROS-1 fusions, BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions should be offered to patients, either as initial or second-line therapy when not given in the first-line setting. New or revised recommendations include the following: Osimertinib is the optimal first-line treatment for patients with activating epidermal growth factor receptor mutations (exon 19 deletion, exon 21 L858R, and exon 20 T790M); alectinib or brigatinib is the optimal first-line treatment for patients with anaplastic lymphoma kinase fusions. For the first time, to our knowledge, the guideline includes recommendations regarding RET, MET, and NTRK alterations. Chemotherapy is still an option at most stages. Additional information is available at www.asco.org/thoracic-cancer-guidelines .

Background Lung cancer is one of the leading causes of cancer mortality in the United States. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced nonsmall cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations and patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. Aims The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. Materials and methods A literature search was conducted on Medline (via PubMed) and National Comprehensive Cancer Network Guidelines using the keywords "precision diagnosis," "advanced non-small cell lung cancer," "target therapies," and "immunotherapy." Conclusion The use of next-generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune checkpoint inhibitors (ICI) leading to better survival rates and lesser toxicity.

Background Sickle cell disease (SCD) is an inherited disorder of red blood cell (RBC) caused by a mutation in the beta-globin gene resulting in abnormal hemoglobin known as hemoglobin S (HbS) or the sickle hemoglobin. Several clinical variants of SCD have been elucidated, all driven by two fundamental pathophysiologic processes: RBC hemolysis and intermittent vaso-occlusive vasculopathy resulting in tissue ischemia/infarction. These two processes underscore the many complications and eventual multi-organ damage that may develop in patients with the most severe types of SCD. Cardiopulmonary complications including heart failure, pulmonary hypertension and acute chest syndrome (ACS) are major drivers of morbidity and mortality among patients with SCD. With regards to ACS, patients often present with fever, cough and shortness of breath caused by vaso-occlusive crisis affecting the lungs. This is particular concerning in view of its similar features to symptomatic COVID-19 infection. Methods We retrospectively identified SCD patients with COVID-19 infection admitted to Beaumont hospitals in Michigan between March 1st 2020 and July 1st 2020. Data was abstracted using the ICD 10 code of U07. 1 for COVID-19, ICD 9 and 10 codes of 282.60 and D57 for sickle cell disease. We excluded patients with sickle cell trait. Data regarding the demographics, presentation, management and outcomes were abstracted. Results A total of eleven patients with sickle cell disease were identified as having a positive SARS-Cov19 polymerase chain reaction test (Table I). All were African American and predominantly female (64%) with a mean age of 44 (22-60) years and mean BMI of 30.2 kg/m2. Genotypes identified were HbSS in 5 (45%) patients, HbSC in 4 (36%), HbS/beta-thalassemia in 1 (9%) and HbS/alpha-thalassemia in 1 (9%). All of the patients had seen a haematologist since their diagnosis but none of the patients were on hydroxyurea, voxeloter, L-glutamine or crizanlizumab at admission. The predominant clinical presentation was fever, chest pain, chills, exertional shortness of breath and cough but this was not consistent across all patients. All the patients were managed with intravenous hydration, pain management as well as hydroxychloroquine/azithromycin per institutional guideline at that time. Three patients (cases 1-3) had recurrent visits to the hospital for similar symptoms and new bone pain crises. Case 1 had a pulmonary embolus which was evident on re-admission. Two patients (cases 3 and 10) succumbed to COVID-19. Two patients (cases 5 and 7) presented with bone pain crisis and no respiratory symptoms, but chest imaging was suggestive of COVID-19 infection necessitating treatment with antibiotics, possibly indicating that the virus can trigger vaso-occlusive crises without respiratory symptoms. Case 8 had a high Charlson comorbidity index and age over 60, had the lengthiest hospital stay complicated by renal failure and polyneuropathy, and was discharged to a long-term acute care facility: an outcome which is consistent with current data showing that the elderly and unfit patients are more likely to have a higher morbidity and mortality with COVID-19. Conclusion To date, there no compelling evidence to provide guidelines for the management of SCD patients with COVID-19. However, following existing recommendations in managing acute chest syndrome and those for COVID-19 symptomatic infection, is a good place to start. We continue to seek to improve management of these patients as new evidence of successful treatment emerges, and also encourage patients to participate in clinical trials. Disclosures No relevant conflicts of interest to declare.

Currently world is fighting with global pandemic of coronavirus disease 2019 (COVID-19). At this time of uncertainty, oncologists are struggling to provide appropriate care to cancer patients. They have to weigh risk and benefit of giving cancer treatment vs chances of getting them infected with COVID-19. As cancer patients are immunocompromised and there are high chances of exposure during hospital visits and if they get infected, outcome can be fatal. So through the column of this article, we would like to provide basic guideline in management of cancer patients during COVID-19 pandemic.

PURPOSE The aim of this work is to provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC) without driver alterations. A guideline update for patients with stage IV NSCLC with driver alterations will be published separately. METHODS The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel made updated recommendations based on a systematic review of randomized controlled trials from December 2015 to 2019. RESULTS This guideline update reflects changes in evidence since the previous guideline update. Five randomized controlled trials provide the evidence base. Additional literature suggested by the Expert Panel is discussed. RECOMMENDATIONS Recommendations apply to patients without driver alterations in epidermal growth factor receptor or ALK. For patients with high programmed death ligand 1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%) and non–squamous cell carcinoma (non-SCC), the Expert Panel recommends single-agent pembrolizumab. Additional treatment options include pembrolizumab/carboplatin/pemetrexed, atezolizumab/carboplatin/paclitaxel/bevacizumab, or atezolizumab/carboplatin/nab-paclitaxel. For most patients with non-SCC and either negative (0%) or low positive (1% to 49%) PD-L1, the Expert Panel recommends pembrolizumab/carboplatin/pemetrexed. Additional options are atezolizumab/carboplatin/nab-paclitaxel, atezolizumab/carboplatin/paclitaxel/bevacizumab, platinum-based two-drug combination chemotherapy, or non–platinum-based two-drug therapy. Single-agent pembrolizumab is an option for low positive PD-L1. For patients with high PD-L1 expression (TPS ≥ 50%) and SCC, the Expert Panel recommends single-agent pembrolizumab. An additional treatment option is pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel). For most patients with SCC and either negative (0%) or low positive PD-L1 (TPS 1% to 49%), the Expert Panel recommends pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel) or chemotherapy. Single-agent pembrolizumab is an option in select cases of low positive PD-L1. Recommendations are conditional on the basis of histology, PD-L1 status, and/or the presence or absence of contraindications. Additional information is available at www.asco.org/lung-cancer-guidelines .

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Recently multiple new therapeutic options have been introduced which was able to improve overall survival but ultimately patient become refractory specifically in patients with poor cytogenetics. Therefore, novel therapeutic options like immunotherapy are needed to improve outcomes. Chimeric antigen receptor (CAR) T-cell therapy is immunotherapy in which T cell are genetically engineered against a tumor-specific antigen and transfused back to the patient to mount major histocompatibility complex-independent cancer-specific immune response. The success of CAR T-cell therapy in lymphoid malignancies encouraged its development in MM. Most of the clinical studies target B-cell maturation antigen in relapsed refractory MM and relapse is the major issue. In this article, we will present the basics of CAR T-cell therapy, the most recent clinical and preclinical data, and we will discuss the future therapeutic realm of CAR T cells in MM.

Historically, patients with locally advanced or metastatic melanoma have an extremely poor prognosis. In recent years, major breakthroughs in cutaneous melanoma treatment have led to remarkable improvements in patient outcomes. However, there are limited published data on the efficacy of these novel therapies in the treatment of mucosal melanoma due to rarity of the disease. We report a case of successful neoadjuvant targeted therapy with BRAF and MEK inhibitors followed by radical surgical excision in a patient with advanced malignant melanoma of the gallbladder.

Acute myeloid leukemia (AML) is a heterogeneous malignancy with diverse genetic abnormalities, clinical presentations, and outcomes. Known predictive and prognostic factors in AML include age, performance status, comorbidities, cytogenetics, and molecular mutations. Identifying prognostic and predictive factors can inform the choice of induction therapy and outcomes prediction.A retrospective review was performed of 137 adult AML patients from 2010 to 2015. Predictors of complete remission (CR) and overall survival (OS) were determined for patients treated with 3+7 (3 days of anthracycline and 7 days of cytarabine) or hypomethylating agent. Variables associated with CR or OS were assessed using univariate Cox regression and a multivariate Cox model.The average age was 65 years and 91 patients (66%), sample size is 137 patients had primary AML. Patients in the 3+7 induction group were younger, had a higher bone marrow blast percentage, and more de novo AML compared with those in the hypomethylating agent group (P .001, P .001, P = .005, respectively). Univariate logistic regression for CR showed a significant association between age (P .001), choice of induction (P .001), and monosomy (P = .015), although only induction with 3+7 (P .001) and absence of monosomy (P = .042) remained significant in multivariate analysis. Univariate Cox regression indicated that age (P = .003), AML status (de novo or secondary; P = .0277), choice of induction (P = .030), and monosomy (P = .010) had a significant association with OS. Only younger age (P = .018) and absence of monosomy (P = .022) were predictive of OS in multivariate Cox analysis.Positive predictors of CR in adult AML include absence of monosomy and induction treatment with 3+7; whereas positive predictors of OS are younger age and absence of monosomy.

Background: Studies using the 21-gene recurrence score (RS) have shown early-stage, low-risk pathologic and genomic breast cancers do not benefit from systemic chemotherapy (CTx) whereas early stage, high-risk breast cancers have improved outcomes when treated with CTx. Data is lacking for patients with discordant risk factors and which feature, genomic or clinical, plays more of a role in determining outcomes. Methods: A retrospective analysis was conducted to identify early-stage breast cancer patients with discordant features, defined as low-risk genomic/high-risk pathologic factors (LG/HP) or high-risk genomic/low-risk pathologic factors (HG/LP), from August 2011–December 2016. LG/HP breast cancer was defined as a RS Results: There were 469 patients with low-risk RS identified of whom 118 (25%) met discordant high-risk pathologic criteria and 62 patients with high-risk RS of whom 14 (23%) met discordant low-risk pathologic criteria. Thirty patients in the LG/HP group received CTx despite a low RS. Of the 118 LG/HP patients, there were 22 (19%) breast cancer recurrences; 21 with locoregional and one with metastatic disease. Of the locoregional recurrences, 10 were contralateral breast whereas 11 were in-breast recurrence despite breast conservation therapy. Of the 14 HG/LP discordant patients, of whom 12 received CTx, 3 (21%) had breast cancer recurrence; one with metastatic disease to the lung and the other two with contralateral breast cancer. Majority of all recurrences occurred >5 years after initial diagnosis. Staging and management depicted below. Management (Mgt) of Discordant Risk Cancers LG/HP initial diagnosis (n=118)LG/HP recurrence (n=22)HG/LP initial diagnosis (n=14)HG/LP recurrence (n=3)Stage 004001A1411142IB14100IIA56500IIB25000IIIA2000IV0101Surgical Mgt Partial mastectomy737102Simple mastectomy431440LN Mgt Sentinel LN biopsy8510132Axillary LN dissection25310Unknown/Not Applicable6800Radiation Mgt Yes816103*No/Unknown351500Hormonal Therapy Yes9417143No/Unknown24500Systemic CTx Neoadjuvant6100Adjuvant242122No/Refused881921*metastatic pt with SBRT to lung Conclusions: Using traditional low-risk RS of 18, we observed more than expected recurrences in our LG/HP discordant patients. Thus suggesting, in patients with discordant results, clinicians must consider both pathologic and genomic factors to optimize patient-specific treatment. Further studies are needed to improve the outcomes of this unique patient population. Citation Format: Blankenship LM, Ezekwudo D, Jaiyesimi I, Stender M, Alassi O, Kresge C, Gaikazian S. Discordant breast cancer: Genomic verse clinicopathologic [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-17.

Malignant melanoma is responsible for the majority of skin cancer deaths and is increasing in prevalence. Bone marrow (BM) involvement by melanoma is rare in the absence of widespread visceral disease. Here, we report the case of a 30-year-old female who presented to the hospital with back pain, low-grade fever, and easy bruising. She was found to be bicytopenic and in disseminated intravascular coagulopathy (DIC). Surprisingly, BM biopsy showed extensive involvement by metastatic malignant melanoma in the absence of visceral or brain metastasis. The unique presentation of this case and the challenge of management of a potentially treatable cancer in a critically ill patient are discussed, alongside a review of published cases of metastatic melanoma in the BM and an exploration of currently available treatment options. The excellent response of our patient to combined immune checkpoint inhibitors has yet to be paralleled in the available literature.

Introduction: The presence of hetero- (sickle trait) or homozygous (sickle disease) hemoglobin S gene is associated with increased risk of venous thromboembolism (VTE). However, sickle disease patients in particular are relatively young, lack common comorbid conditions that would qualify them for inpatient VTE prophylaxis (VTEP) and there are limited published data on trends of VTEP use in these populations. Methods: This was a retrospective analysis of all hospitalizations of sickle trait or disease adult medical patients occurring between January 2013 and December 2018 at three hospitals in Southeast Michigan, USA. Admissions for bleeding or thrombosis, requirement of intensive care stay or surgery, those occurring within 45 days of orthopedic surgery, as well as all patients already on anticoagulation or with known hypercoagulable states were excluded. Hospitalized controls were matched for race, age, sex and length of stay. Trends of VTEP use and predictive patient factors over multiple admissions were modeled using generalized estimating equations. Results: There were 803 sickle trait (525 patients; mean age 43 ± 19; 85% female) and 1020 sickle disease admissions (262 patients; mean age 34 ± 13; 57% female); all patients were Black. The percentage of hospitalizations in which subjects were offered any VTEP was similar to that of controls in both groups of interest (Figure); however, there were more encounters in which patients received greater than 50% of expected VTEP doses in the sickle trait (80% vs 51%; p Conclusions: VTEP is underused in sickle trait and disease patients. There may be a trend towards offering more VTEP in sickle disease, but not in sickle trait, where the decision is driven by comorbid conditions rather than hemoglobin genotype. Patient refusal does not appear to play a major role, but the finding of significant inter-center variability suggests provider education may result in improved use as hemoglobin genotype is currently not part of risk stratification tools that help clinicians decide on inpatient VTEP. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Hypercoagulability may contribute to COVID-19 pathogenicity. Evidence comparing clinical outcomes among patients with COVID-19 receiving therapeutic compared to prophylactic dose anticoagulation is limited. We evaluated whether therapeutic anticoagulation (tAC) is associated with improved survival compared to prophylactic (pAC) and no anticoagulation (AC) in hospitalized COVID-19 patients. Methods: This was a retrospective, multi-center cohort study of consecutive COVID-19 patients admitted between March 13th, 2020 and May 5th, 2020 to eight hospitals within a large academic system in Southeast Michigan, USA. Participants were assigned to three groups based on whether they received no AC, pAC throughout most of their hospitalization, or at least 3 days of tAC. Major bleeding was defined as transfusion of five or more units of packed red blood cells within 48 hours regardless of hemoglobin level, hemoglobin < 7g/dL and any red blood cell transfusion or a diagnosis code for major bleeding during the hospitalization or radiological evidence of intracranial hemorrhage Results: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n=642) were treated in the intensive care unit (ICU). 60.9% received pAC (n=2121), 28.7% received at least 3 days of tAC (n=998), and 10.4% (n=361) did not receive AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated a statistical difference in the 25-day survival probability in the tAC group compared to the pAC group (57.5% vs 50.7%, Figure). In a PS weighted multivariate proportional hazards model adjusting for age, body mass index and ICU status, AC was associated with a reduced risk of death at both prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently among tAC patients (81 [8.1%]) compared to those who received no AC (20 [5.5%]) or pAC (46 [2.2%]). Conclusions : Higher doses of AC are associated with lower mortality in hospitalized COVID-19 patients. The lowest hazard ratio was observed in ICU patients, but risk was also significantly lower in non-ICU hospitalized patients. Bleeding occurred more frequently with higher doses of anticoagulation. Ongoing randomized trials are warranted to prospectively evaluate efficacy and risk of tAC in patients with COVID-19. Figure Disclosures No relevant conflicts of interest to declare.

Introduction COVID-19 in patients with hematologic malignancies are poorly characterized. Theoretically, it is believed that patients with malignancies having a significant chance of succumbing to COVID-19 due to the immunosuppression from the disease and myelosuppression from the cancer therapy compared to their counterparts without malignancies. However, there is scant evidence to support this claim. Here we analyze the outcomes of patients with hematologic malignancies and COVID-19. Methods This is a retrospective review of all patients with hematologic malignancies with confirmed COVID-19 admitted to any one of the Beaumont hospitals in Michigan between March 1st,2020 and July 1st ,2020. Data regarding the demographics, cancer diagnosis and management, covid-19 management and outcomes were abstracted. Results A total of 32 patients with hematologic malignancies were identified. Of these 32 patients, five patients also had solid malignancies. Median age was 70.5 years (22-91 years) with patients being predominantly female 18 (56 %) and Caucasians 16 (50%). Median BMI was 26.5 kg/m2 (15-79 kg/m2). The most prevalent hematologic malignancies were Chronic/Small Lymphocytic lymphoma 7(25%) and Multiple Myeloma 6(19%). The median length of stay in the hospital was 9 days (2-61days). Twelve patients were on active therapy prior to COVID-19 diagnosis. Therapies administered include radiation, surgery, anti-CD30 antibody drug conjugate, immunomodulatory agents, proteasome inhibitors, Bruton tyrosine kinase inhibitors, steroids and chemotherapy. These agents were held at the time of diagnosis of COVID-19 Twenty two patients (69%) patients received a combination of hydroxychloroquine and azithromycin which were standard of care at that time. A total of 31 (97%) patients were on anticoagulation of which 14 (45%) were on therapeutic doses while 17 (55%) were on prophylactic dose. Four (13%) of the patients were admitted in the ICU. A total of 6 deaths were reported and the median age was 83 years (66-91 years). Four deaths were attributed to COVID-19. Two non-COVID-19 deaths were as a result of aspiration pneumonia and hospital acquired pneumonia. Only one patient with COVID-19 received treatment for malignancy (surgical cytoreduction) but succumbed to COVID-19 four days later. All patients who died received a combination of hydroxychloroquine and azithromycin. Conclusion Our study, though limited by sample size, shows that about a third of patients received treatment for their hematologic malignancies around the time of COVID-19 diagnosis and only one death was reported. Patients are currently being advised to participate in clinical trials to better evaluate outcomes while on treatment for hematologic malignancies. Disclosures No relevant conflicts of interest to declare.

Background Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening condition caused by the binding of platelet-activating antibodies (IgG) to multimolecular platelet factor 4 (PF4)/heparin complexes because of heparin exposure. The by-product of this interaction is thrombin formation which substantially increases the risk of venous and/or arterial thromboembolism. Currently, only one anticoagulant, argatroban, is United States Food and Drug Administration-approved for management of HIT; however, this agent is expensive and can only be given by intravenous infusion. Recently, several retrospective case-series, case reports, and one prospective study suggest that direct oral anticoagulants (DOACs) are also efficacious for treating HIT. We further review the literature regarding current diagnosis and clinical management of HIT. Case presentation A 66-year-old male patient developed HIT beginning on day 5 post-cardiovascular surgery; the platelet count nadir on day 10 measured 16 × 109/L. Both the PF4-dependent ELISA and Serotonin-release assay were strongly positive. Despite initial anticoagulation with argatroban (day 6), the patient developed symptomatic Doppler ultrasound-documented bilateral lower extremity deep vein thrombosis on day 14 post-surgery. The patient was transitioned to the DOAC, apixaban, while still thrombocytopenic (platelet count 108) and discharged to home, with platelet count recovery and no further thrombosis at 3-month follow-up. Conclusions We report a patient with serologically confirmed HIT who developed symptomatic bilateral lower limb deep vein thrombosis despite anticoagulation with argatroban. The patient was switched to oral apixaban and made a complete recovery. Our patient case adds to the emerging literature suggesting that DOAC therapy is safe and efficacious for management of proven HIT.

We report a case of primary diffuse large B-cell lymphoma of the prostate in a 54-year-old Caucasian male who presented with urinary retention and benign prostatic hyperplasia. We discuss the rare presentation of this disease and its clinicopathologic features and review the literature for up-to-date information on the diagnosis and clinical management. Despite the low incidence of lymphoma involving the prostate gland, it should always be considered as part of the differential diagnosis in cases of prostate gland enlargement with urinary tract obstructive symptoms resistant to medical therapy. Treatment modalities for this rare disease are also discussed.

Purpose Successful immuno-oncology research over the past few decades has driven the widespread clinical application of immune checkpoint inhibition, the activation of the bodies’ immune system to combat malignant tumor cells, in the management of various cancers. The utilization of the checkpoint inhibition mechanism in the treatment of advanced non-small cell lung cancer (NSCLC) became the standard second-line therapy in 2015 with the FDA approval of Nivolumab and Pembrolizumab. Design This review provides a synopsis of the existing knowledge of the role of the immune system in the pathogenesis of malignant tumors and examines the mechanism of action of immune therapies, as well as discussing the data from the clinical studies responsible for the approval of immune checkpoint inhibition in the treatment of advanced NSCLC. Results Three recently-approved drugs: Nivolumab, Pembrolizumab and Atezolizumab, and Durvalumab, currently under FDA review, have shown favorable overall survival, overall response rate, duration of response and/or toxicity/safety profiles in a number of single agent and combination therapy clinical trials compared to standard of care platinum-based doublet chemotherapies for advanced NSCLC patients who have metastatic disease, have failed standard-of-care therapy, or are treatment-naive. Conclusion Current and future research will focus on novel immunotherapeutic agents and additional drug combination trials, as well as investigating tumor-specific biomarkers, including PD-L1 expression and other immune signatures, to predict which patients may best benefit from the new checkpoint inhibition drug regimens. In the near future, clinicians will have more choices of potential first line treatment regimens for NSCLC patients, and eventually targeted therapies and immunotherapy may prove more efficacious and safer than current platinum-based chemotherapy.