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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

HER2-positive breast cancer is an aggressive subtype of breast cancer with five-year survival rates of 30% for the advanced stage. The development of anti-HER2 treatments has led to a paradigm shift in the management and clinical outcomes of advanced HER2-positive breast cancer patients. The standard first-line treatment consists of taxane-based chemotherapy plus dual anti-HER2 therapies with trastuzumab and pertuzumab. The antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) has been a second-line therapeutic standard, but the second-line treatment approach is rapidly evolving. Given a substantial advantage of another ADC, Fam-trastuzumab deruxtecan (T-DXd), compared to T-DM1 in a recent randomized trial in the second-line setting, T-DXd is currently the preferred second-line option. Optimal third-line treatment strategies are still not established, and multiple approaches have been used including combinations based on capecitabine, trastuzumab, or both with oral anti-HER2 tyrosine kinase inhibitors. Tucatinib plus capecitabine and trastuzumab, lapatinib plus trastuzumab, neratinib or lapatinib plus capecitabine are some of the FDA approved combinations. Another newer agent approved for third- or later-line therapy in the metastatic setting is margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, in combination with chemotherapy. Other novel agents currently under clinical trials are the drugs that indirectly target HER2, including immune cell cycle inhibitors, PI3K/mTOR inhibitors, and immunotherapy agents.

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.

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.

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.

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.

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.

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.

Breast implant–associated anaplastic large T-cell lymphoma has recently been recognized as an entity, with few reports describing the two common subtypes: in situ (indolent) and infiltrative. Recently, the infiltrative subtypes have been shown to be more aggressive requiring adjuvant chemotherapy. We report a rare case of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) in a 65-year-old Caucasian female following silicone breast implantation and multiple capsulectomies. We discuss the rare presentation of this disease, histopathologic features of the indolent and infiltrative subtypes of ALCL, and their clinical significance. We also review the literature for up-to-date information on the diagnosis and clinical management. Treatment modalities including targeted therapy are also discussed. Although BIA-ALCL is rare, it should always be considered as part of the differential diagnosis especially in women with breast implants. Given the increasing rate of breast reconstruction and cosmetic surgeries, we anticipate a continuous rise in incidence rates of this rare disease; thus, caution must be taken to avoid misdiagnosis.

A number of important drugs used to treat cancer—many of which serve as the backbone of modern chemotherapy regimens—have outdated prescribing information in their drug labeling. The Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of knowledge the cancer community has accumulated with the use of these drugs over time. This article highlights a number of considerations for labeling updates, including selecting priorities for updating; data sources and evidentiary criteria; as well as the risks, challenges, and opportunities for iterative review to ensure prescribing information for oncology drugs remains relevant to current clinical practice., The U.S. Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for long‐standing oncology drugs. This article highlights a number of considerations for labeling updates.

Background and objectives Patients with T4 colon adenocarcinoma have an increased risk of locoregional and distant recurrence. This study defines the metastatic pattern, predictors of recurrence, and efficacy of adjuvant treatment in T4 colon cancer. Methods A retrospective review was performed of patients with T4 colon adenocarcinoma from May 2005 to November 2015 at a tertiary care hospital. Baseline factors, follow-up, recurrence, and survival were collected and analyzed. Results Locoregional recurrence (LR) rates for N0, N1, and N2 were 21/85 (24.7%), 14/50 (28%), and 21/46 (45.7%), respectively (P = .014). Multivariate analysis for distant recurrence was significant for positive nodes (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.1-9.9). Multivariate analysis for LR was significant for the following variables: perforation (HR, 2.7; 95% CI, 1.2-6.2), lymphovascular invasion (HR, 2.7; 95% CI, 1.1-6.7), positive nodes (HR, 2.8; 95% CI, 1.2-6.9), and positive margins (HR, 5.0; 95% CI, 2.1-12.1). Multivariate analysis for overall survival was significant for: signet ring histology (HR, 2.5; 95% CI, 1.2-5.8), positive nodes (HR, 2.3; 95% CI, 1.2-4.4), and positive margin (HR, 2.8; 95% CI, 1.4-5.8). Conclusion T4 colon adenocarcinoma has a high risk of LR and mortality. Clinical trials utilizing the aforementioned high-risk features may increase the ability to demonstrate beneficial intervention.

Poster: "RANZCR-AOCR 2012 / R-0001 / The Correlation between Lymphoma Cell Size and PET-CT Metabolic Activity in Follicular Lymphomas" by: "C. Y. O. Wong, G. Brahmanday, M. M. Chisti, A. Muslimani, I. Jaiyesimi, P. Rigo, B.-T. Hung, P.-L. Khong, J. Huang"

Indolent lymphomas may transform into intermediate or high-grade lymphoma, a diagnosis that is usually made reached by tissue biopsy, with unfavorable prognosis. A retrospective study was performed of the clinical characteristics, treatment patterns and outcomes of 73 patients with histologic transformed lymphoma originating as follicular lymphoma (FL), chronic lymphocytic leukemia/small cell leukemia (CLL/SCL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), or low grade B cell lymphoma not otherwise specified (NOS). The median time to transformation was 55 months (range 1-258) and Diffuse Large B Cell Lymphoma (DLBCL) constituted the majority of HTL diagnosis diagnoses. There was a statistically significant longer time to the development of HTL in patients with CLL and LPL compared to other indolent lymphoma types (FL, MZL and low-grade B cell lymphoma NOS); however, overall survival (OS) at histologic transformation was similar regardless of the indolent lymphoma type preceding HTL. Treatment with Rituximab-containing regimens have increased overall survival in HTL compared with the pre-rituximab era. In the 63 treated cases of HTL, PET showed complete remission (CR) in the majority of patients (55%) with 15% achieving partial remission (PR) and 15% having progressive disease (PD). OS at two years was approximately 60%, and 41% of patients remained alive at 5 years. Univariate analysis identified that treatment with RCHOP conferred better OS when compared to regimens with less or greater intensity than RCHOP, p=0.001. Multivariate analysis confirmed that achievement of CR and LDH level within the normal range statistically predicted better OS. On-going clinical trials may suggest novel therapeutics and provide for more evidence-based management of HTL.

We aim to review the use of molecular markers for risk stratification and to describe the current standard and new targeted treatment options for the subgroup of patients with 17p deletion chronic lymphocytic leukemia (CLL) with an accompanying TP53 mutation, known as “double hit” CLL. Chromosome 17p deletion is seen in 5-9% of patients with newly diagnosed CLL; however, it represents the most common genetic aberration (≈50%) in patients with refractory/relapsed CLL. Identification of genomic and molecular markers allows risk stratification and has prognostic value. Chromosome 17p deletion has been strongly correlated with poor response to standard therapy as well as shorter overall survival. Accompanying TP53 mutation confers an even poorer response to standard therapy than 17p deletion alone. A review of current treatment options reveals the ongoing debate as to the appropriate timing of treatment initiation in this patient subpopulation. Moreover, standard treatment options still confer suboptimal benefit. Small molecule inhibitors targeting intracellular B-cell receptor signaling components such as Bruton’s tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), anti BCL-2 molecules, and more recently CD19-targeted CAR T-cell therapy, have shown significant progression-free survival and overall survival advantages in patients with 17p deletion and/or TP53 mutation, while allogeneic hematopoietic cell transplant has proven clinical benefit in selected patients.

3593 Background: Doublet chemotherapy FOLFOX and FOLFIRI are standard for first‐line treatment of metastatic colorectal cancer (mCRC). Recently, use of triplet chemotherapy FOLFOXIRI has shown an increased anti-cancer activity but still there is uncertainty regarding first line backbone chemotherapy. Therefore, we conducted this metanalysis to determine the efficacy, safety and outcome of triplet vs doublet chemotherapy. Methods: The study protocol was published at PROSPERO (CRD42020166745) and prepared as per PRISMA guidelines. Total 10 studies were included, with sample size of 1536 participants in triplet arm and 1535 participants in doublet arm. The primary outcome is Response rate (RR) and secondary outcomes are Progression-free survival (PFS), Overall survival (OS), post chemotherapy radical (R0) surgical resection rate of metastases. Quantitative synthesis was performed using “R” statistical package. Dichotomous outcomes were summarized using odds ratio (OR) and time to event data was summarized using hazard ratio (HR). Results: A total of 678 articles were retrieved. The Medline article search gave a result of 271 article, Embase 296, the Cochrane Library 100 and Clinical tral.gov 11, when searched through April 2020. Total 10 studies were included. All the studies were randomized, open-label, multicenter study. Out of the 10 trials 5 each were phase II and phase III studies. The pooled odds ratio for RR was 1.66 (95% CI 1.42 to 1.93) and PFS was (HR, 0.70; 95% CI, 0.63–0.78) in favor of triplet chemotherapy. There was significant improvement in radical resection (R0) of metastases (OR 1.59; 95% CI, 1.27–1.98) in triplet arm. Triplet arm was also associated with increased toxicity especially neurological events 2.51(0.88-7.16), diarrhea 2.40(1.74-3.31), neutropenia, 2.23(1.71-2.90) and thrombocytopenia 1.94(1.05-3.59). Conclusions: Findings in this meta-analysis showed that FOLFOXIRI significantly improves the PFS, RR, OS, and R0 resection rate of overall metastases over the doublet chemotherapy. The incidence of fatal adverse events was found to be more in triplet chemotherapy compared to doublet therapy. Therefore, we concluded that with moderate evidence FOLFOXIRI provide clinically meaningful efficacy benefit at cost of increased toxicity.[Table: see text]

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from the fusion of the BCR-ABL genes, forming the Philadelphia chromosome. The diagnosis is often suspected when there is leukocytosis with left shift and basophilia. Confirmation of the diagnosis requires a demonstration of BCR-ABL by polymerase chain reaction. Using data from the William Beaumont laboratory data registry, we conducted a retrospective review of all the orders for BCR-ABL tests sent to the clinical pathology laboratory between March 11, 2014 and September 12, 2014. We concluded that the presence of concurrent neutrophilia and basophilia has a sensitivity of 100% (95% CI, 69.15% to 100%) and specificity of 100% (95% CI, 93.15% to 100%) in the initial diagnosis of CML. Our results suggest that the presence of both neutrophilia and basophilia should be used as a threshold for the placement of orders for BCR-ABL in the initial diagnosis of CML in patients with leukocytosis with left shift and provide a basis for a reduction in health care spending. Restricting BCR-ABL tests to this population would save approximately $198 million annually in national health care spending.

e17101 Background: Renal cell carcinoma (RCC) with sarcomatoid differentiation is a highly aggressive form of RCC. The presence of even a small component of sRCC was shown to independently predict poor survival compared to RCC without sarcomatoid features. We studied the epidemiology and survival outcome of sRCC compared to ccRCC by reviewing the SEER data. Methods: Patients (pts) with histologically confirmed sRCC and ccRCC between 2012-2015 were reviewed in SEER database. Variables included age, gender, ethnicity, histologic grade, stage at diagnosis, and nephrectomy. Primary outcome was 5 year Disease Specific Survival (DSS). Data was analyzed using Kaplan Meier curves and Cox proportional hazards model. Results: A total of 31, 293 pts with RCC were identified in SEER database between 2012 to 2015. 611 pts had sRCC while 30, 682 had ccRCC. The two groups had almost similar demographic features, including mean age (63 ±12 for sRCC vs 61±12 years for ccRCC), male: female ratio (vs 2.3:1 vs 1.7:1) and Caucasian ethnicity (82% vs 85%). More than half of sRCC patients (62%) were metastatic at diagnosis compared to only 11% of ccRCC, which presented most commonly as stage I disease (63%). The histologic grade was higher in sRCC patients (43% grade 4 vs 45% grade 2 in ccRCC subjects). Nephrectomy rates were almost similar for stages I-III in the two groups (94% in sRCC vs 93% in ccRCC) while lower in stage IV sRCC (44% vs 54%). Across all stages and at every time point, sRCC was associated with increased mortality in the univariate analysis. In the multivariate regression analysis (table), advanced stage was the strongest independent predictor of mortality (HR 11.9), followed by high histologic grade (HR 3.6) and sarcomatoid histology (HR 2.9). Nephrectomy was protective (HR 0.3). Age was associated with worse outcomes (HR 1.016 per unit change). Conclusions: sRCC are more aggressive and tend to present as metastatic disease. sRCC has worse outcomes across all stages compared to ccRCC even after adjusting for potential confounders. Advanced stage and histologic grade remain the two strongest predictors of disease-specific mortality, sarcomatoid histology demonstrated a significant impact on outcome. [Table: see text]

1537 Background: Heterozygous germline ATM mutation carriers have an increased risk of developing breast, pancreas, and other cancers. The clinical and pathologic characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing (MGPT) between 2013-2019 and identified to harbor ATM mutations were included in the study. We evaluated demographics, pathology, and surgical management of our ATM mutation carriers with breast cancer. Results: At total of 319 individuals were identified to have variants in ATM, of which 114 were pathogenic/likely pathogenic. The majority of patients were female (82%) and Caucasian (88%). A total of 56 patients (49%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 39). Nine individuals had more than one primary malignancy. The mean age at breast cancer diagnosis was 52, with a range of 25-82. The majority of patients had invasive ductal carcinoma (74%), grade 2 or 3 (90%), and ER and /or PR positive (87%). Of those with known HER2 status, 24% were positive. Thirty-nine percent of patients were lymph node positive, and 42% had lymphovascular invasion. The most common stage at diagnosis was 2 (53%). Of the 39 mutation carriers with breast cancer, 16 (42%) received radiation therapy, and 16 underwent bilateral mastectomy. Of 114 ATM positive patients, there were 55 distinct variants. Sixteen (14%) individuals had a mutation in additional cancer predisposition genes. One variant, c.5015delG, was identified in ten patients in a large, consanguineous Iraqi family with an extensive history of pancreatic and other cancers. Eight individuals were identified to have the known high-penetrance variant, c.7271T > G. Conclusions: Our study describes the clinical and pathological characteristics of ATM mutations carriers with breast cancer. The majority of patients had intermediate to high grade disease, hormone receptor positive, with a suggestion of a higher rate of HER2 positivity and lymph node involvement. Additional studies are needed to elucidate the unique characteristics of ATM-associated breast cancer, which may have implications for personalized management.

e21509 Background: Patients with epidermal growth factor receptor (EGFR) mutated lung cancer have an excellent prognosis compared to other non-small cell lung cancer (NSCLC) with no driver mutation, however, there is a wide range of survival between even a cohort with an EGFR driver mutation. Given that many patients with EGFR mutations are never smokers, it is possible that those with a smoking history have tumors with other oncogenic mutations and therefore as their tumors are less dependent on the EGFR driver, they may derive less benefit from targeted therapy. Methods: Pathology specimens of NSCLC sent for EGFR testing between January 1 2012 and December 31 2016 at Beaumont Hospital, Michigan were reviewed. If a tumor harbored a targetable EGFR mutation, the chart was queried. Inclusion criteria were EGFR exon 19 or 21 mutations, stage IV disease, at least 2 time points of follow up. Exclusion criteria included small cell histology, negative EGFR test, or inadequate information in the chart. The primary endpoint of the study was median survival. Results: Out of 329 cases identified, 40 were positive for EGFR exon 19 or 21 mutations. Of the 40 positive cases, 26 fit all inclusion criteria. Median duration of follow up was 14 months (range 0-80). Smokers represented 13/26 (50%) of cases. Death occurred in 9/13 (69%) of smokers vs 7/13 (54%) in non-smokers. Median survival was 8 mo (0-26) vs 20 mo (1-80) respectively for smokers vs non-smokers. Conclusions: This data suggests there may be a clinically relevant difference in the survival between smokers and nonsmokers who have NSCLC with an EGFR driver mutation. This may be due to the relatively low burden of alternative driver oncogene mutations in the nonsmoker’s tumors resulting in a lower likelihood of an escape mechanism for the tumor to survive. Further analysis of larger datasets with complete molecular analysis of the tumors would be informative in exploring this hypothesis. This would aid in risk stratifying patients more effectively for future clinical trials targeting the EGFR mutation and refining the prognosis in this otherwise good prognosis group.

Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care’s update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development. Recommendations New or revised recommendations include the following. Regarding first-line treatment for patients with non–squamous cell carcinoma or squamous cell carcinoma (without positive markers, eg, EGFR/ALK /ROS1), if the patient has high programmed death ligand 1 (PD-L1) expression, pembrolizumab should be used alone; if the patient has low PD-L1 expression, clinicians should offer standard chemotherapy. All other clinical scenarios follow 2015 recommendations. Regarding second-line treatment in patients who received first-line chemotherapy, without prior immune checkpoint therapy, if NSCLC tumor is positive for PD-L1 expression, clinicians should use single-agent nivolumab, pembrolizumab, or atezolizumab; if tumor has negative or unknown PD-L1 expression, clinicians should use nivolumab or atezolizumab. All immune checkpoint therapy is recommended alone plus in the absence of contraindications. For patients who received a prior first-line immune checkpoint inhibitor, clinicians should offer standard chemotherapy. For patients who cannot receive immune checkpoint inhibitor after chemotherapy, docetaxel is recommended; in patients with nonsquamous NSCLC, pemetrexed is recommended. In patients with a sensitizing EGFR mutation, disease progression after first-line epidermal growth factor receptor tyrosine kinase inhibitor therapy, and T790M mutation, osimertinib is recommended; if NSCLC lacks the T790M mutation, then chemotherapy is recommended. Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib, or if they previously received crizotinib, they may be offered chemotherapy.

During induction treatment, acute myeloid leukemia patients may develop pulmonary infiltrates due to infectious or noninfectious etiologies. The risk association and the clinical outcome of such pulmonary infiltrates are poorly characterized in the literature.We retrospectively reviewed 363 cases of acute myeloid leukemia patients who received induction therapy as inpatients over a period of 11 years at William Beaumont Health System. Of these 363 patients, 120 developed pulmonary infiltrates during induction therapy, those patients were divided into 2 groups based on distribution of the infiltrate presenting as localized or diffuse in nature. Data on patients characteristics, leukemia subtype, cytogenetic risk, microorganism type, white blood cell count at diagnosis, neutrophil count at the time the infiltrate was reported, response to antibiotic and/or antifungal therapy, using respiratory support, and mortality rate were retrieved through chart review.Thirty-three percent of patients developed pulmonary infiltrates during their induction therapy. Sixty-three patients (52.5%) had a localized infiltrates and 57 patients (47.5%) had diffuse infiltrates. Of the 120 patients with pulmonary infiltrates, 48 (40%) had at least 1 pathogenic microorganism identified, and 58 (48.7%) required intubation and ventilatory support. Patients with localized pulmonary infiltrates were more likely to have positive pathogenic microorganisms (68.3% vs. 8.8%, P0.001), to be neutropenic (96.8% vs. 21%, P0.001), and tended to have potentially reversible infiltrates after treatment (87.3% vs. 21%, P0.001). Whereas patients with diffuse infiltrates were more like to require intubation (78.9% vs. 21%, P0.001), to have leukocytosis (white blood cell100 billions/L) at diagnosis (54.4% vs. 0%, P0.001), and had a higher mortality rate (70.2% vs. 9.5%, P0.001).The radiologic patterns of pulmonary infiltrates showed specific etiological and prognostic associations. Diffuse infiltrates are an unfavorable characteristic with overall dismal outcome.

Background. Obesity is a major epidemic affecting all age groups in the USA. It has been associated with venous thromboembolism (VTE), which requires prolonged anticoagulation. Classic options (vitamin K antagonists, heparins) are increasingly replaced by direct oral anticoagulants (DOACs), which have not been well studied in patients with body mass index (BMI) > 40kg/m2 or weight above 120 kg. Despite limited safety and efficacy data, patients and their caregivers often opted for this medication owing to its ease of administration, lack of requirement for frequent laboratory testing and for dietary restrictions. Methods. This is a retrospective study of all morbidly obese patients (BMI > 40kg/m2) diagnosed with acute VTE managed with DOACs at Beaumont hospital between January of 2018 and December of 2018. Data regarding demographics, specific DOAC, major bleeding (hemoglobin decrease by 2 g/dL) and new or progressive thrombosis were recorded during a sixty-day follow up. Data was analyzed using JMP statistical software. Results A total of 42 patients diagnosed with acute VTE received DOACs during the study period. Most were female (76%); the median BMI was 44 (IQR 42-60) and mean age was 57. Most patients had a BMI of 40-50 kg/m2 (n=34, 81%) compared to BMI 50-60 kg/m2 (n=6, 14%) and BMI >60kg/m2 (n=6, 14%). Apixaban was the most frequently used DOAC (n=27, 65%). No clinically significant bleeding occurred during the study period. There were 2 thrombotic episodes (5% of patients) within 60 days of starting a DOAC; both occurred in patients receiving rivaroxaban. One event was present in the BMI 40-50kg/m2 group and one in the >60kg/m2 group. Conclusions DOACs appear to be safe and efficacious for the management of VTE in the morbidly obese population. Future studies may focus on the comparative efficacy of apixaban and rivaroxaban in the morbidly obese population. Disclosures No relevant conflicts of interest to declare.

Background: Heparin-induced thrombocytopenia (HIT) occurs as a result of autoantibodies to the platelet factor 4 (PF4)-heparin complex, which activate the coagulation cascade with subsequent thrombosis. HIT can be fatal if not diagnosed and treated promptly with replacement of all heparin with non-heparin anticoagulants. Classic options are parenteral direct anti-thrombin agents which require intravenous administration and can prolong hospital stay. Direct oral anticoagulants (DOACs) address these inconveniences and are an interesting alternative. However, data regarding their efficacy and safety in HIT is limited. Methods: We retrospectively identified patients with HIT using ICD code 9: 289.84 and ICD code 10: D75.82 at Beaumont Hospital (Royal Oak) between December 2013 and December 2018. Only patients with HIT confirmed by positive serotonin release assay and managed with DOACs were included. Data regarding diagnostic tests, bleeding and thrombosis during the 30-day follow-up were recorded. Results: A total of 229 patients were identified using the ICD codes; only 8 patients had confirmed diagnosis of HIT and were treated with DOACs. The average age was 70 years (51-92 years); most were male (5, 62.5%) and Caucasian (6, 75%). The median optical density of PF4-heparin antibody was 1.97 (0.85-3.108). Six patients (75%) had confirmed HIT-associated thrombosis; one had negative Doppler ultrasonography of the lower extremities (upper extremities were not assessed) and one patient was not assessed for thrombosis. Seven patients (87.5%) received apixaban and one patient received rivaroxaban. The lowest platelet count prior to initiating DOAC was 40,000/microL, while three patients started DOACs when their platelet count was above 150,000/microL. Within the follow-up period, none of the patients on apixaban had bleeding episodes or clot progression. The only patient treated with rivaroxaban was re-admitted within one week of discharge for right upper extremity deep vein thrombosis. Unfortunately, this was the one patient who was not evaluated for thrombosis at the time of HIT diagnosis. Conclusion: In the 30 days following HIT diagnosis, treatment with apixaban resulted in adequate anticoagulation and was not associated with increased bleeding events despite relative thrombocytopenia. Disclosures No relevant conflicts of interest to declare.