Genomic determinants in advanced endometrial cancer patients with sustained response to hormonal therapy- case series and review of literature.

The incidence of endometrial cancer is increasing, however treatment options for advanced disease are limited. Hormonal therapy has demonstrated positive outcomes for Stage IV EC. Next generation sequencing (NGS) has increased our understanding of molecular mechanisms driving EC. In this case series, we selected six patients at our institution with Stage IV, hormone receptor positive, endometrial cancer currently being treated with hormonal therapy. All patients achieved SD for at least ≥ 1.5 years. We studied NGS data on all six patients to assess for any common genomic marker which could predict the SD of at least 1.5 years achieved in this group. Institutional Review Board (IRB) approval was obtained from Staten Island University Hospital and Northwell Health, New York. PTEN, PIK3CA, PIK3R1, and ARID1A mutations were found in 83%, 67% 50%, and 67% of patients respectively. TP53 and FGFR2 were both found in 50% of patients. All patients were positive for estrogen and/or progesterone receptor (ER+ and/or PR+). We did not find any one common mutation that could have predicted the observed response (or SD of ≥1.5 years) to hormone therapy. However, our data reflects the prevalence of various mutations reported in literature: (1) Hormone Receptor status is a positive prognostic indicator (2) PTEN/PIK3CA mutations can occur concurrently in EC (3) ARID1A coexists with PTEN (4) FGFR and PTEN pathways may be interlinked. We suggest NGS be employed frequently in patients with endometrial cancer to identify targetable mutations. Additional larger studies are needed to characterize the interplay between mutations.

Synchronous thyroid cancer and malignant struma ovarii: concordant mutations and microRNA profile, discordant loss of heterozygosity loci.

BACKGROUND: Struma ovarii is an unusual ovarian teratoma containing predominantly thyroid tissue. Less than 10% of cases undergo malignant transformation in the thyroid tissue and are considered malignant struma ovarii (MSO). MSO have been reported with concurrent thyroid lesions, but molecular data is lacking. CASE PRESENTATION: A 42-year-old female developed MSO and synchronous multifocal subcentimeter papillary thyroid carcinoma (PTC). The patient underwent a salpingo-oophrectomy, thyroidectomy, and low-dose radioactive iodine ablation. Both the thyroid subcentimeter PTC and MSO were positive for BRAF V600E mutation, and microRNA expression profiles were similar across all tumor deposits. However, only the malignant component demonstrated extensive loss of heterozygosity (LOH) involving multiple tumor suppressor gene (TSG) chromosomal loci. CONCLUSIONS: We present the first reported case of MSO with synchronous multifocal subcentimeter PTC in the thyroid containing concordant BRAF V600E mutations and resulting with discordant LOH findings. This data suggests that loss of expression in tumor suppressor gene(s) may be an important contributor to phenotypic expression of malignancy.

Efficacy of PARP Inhibitors as Maintenance Therapy for Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials.

Background: PARP inhibitors have been recently approved by the FDA for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Their effectiveness is seen when used with androgen deprivation therapy in patients with or without deleterious germline and somatic genetic mutations. Objectives: To identify all the randomized controlled trials (RCTs) in which PARP inhibitors have been assessed in the treatment of mCRPC, and to compare the efficacy of PARP inhibitors in these patients with standard-of-care (S/nonhormonal therapies like abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in terms of progression-free survival (PFS) and overall survival (OS). Search strategy: A systemic review search was conducted using PubMed, Embase, and Central Cochrane Registry. Selection criteria: Randomized clinical trials with PARP inhibitors, with or without antihormonal therapy, as the intervention arm, with SOC as control. Data analysis: HRs were calculated for PFS and OS. For effect sizes, a confidence interval of 95% was used, and for statistical significance, a P value of less than .05 was used. Analysis was done using random effects and fixed models and both were reported. Heterogeneity was evaluated using I2 statistic. Results: Three RCTs were included in the analysis. PARP inhibitors showed a statistically significant improvement in OS when calculated using a fixed model (HR, 0.751; 95% CI, 0.582-0.968) but the improvement was not significant when calculated using a random model (HR, 0.758; 95% CI, 0.565-1.017; I2 = 23). Similarly, the improvement in PFS was statistically significant when calculated using a fixed model (HR, 0.626; 95% CI, 0.521-0.752), and no statistical significance was noted with a random model (HR, 0.674; 95% CI, 0.437-1.039; I2 = 80). Conclusions: PARP inhibitors contributed to significant increases in PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide. This efficacy was pronounced among the patients with deleterious germline or somatic homologous recombination repair gene mutations, although patients without these mutations also showed a better PFS and OS in comparison with SOC therapy.

Hemophagocytic Lymphohistiocytosis Associated with Respiratory Syncytial Virus Infection in an Immunocompetent Elderly Patient.

Hemophagocytic lymphohistiocytosis is a serious and potentially fatal disorder characterized by excessive immune system activation. The disorder is diagnosed mainly based on laboratory, clinical, and pathologic criteria. The spectrum comprises hereditary or "primary" HLH that comprises genetically heterogeneous conditions, occurring during childhood. The secondary form presents later in life and is associated with several conditions mainly malignancy, autoimmune diseases, viral or bacterial infections, and hematological diseases. We present the case of an 80-year-old female patient who initially presented with an acute viral syndrome secondary to respiratory syncytial virus. The hospital course was complicated by disseminated intravascular coagulation and shock with multiorgan failure. Extensive workup revealed that several of the criteria for hemophagocytic lymphohistiocytosis were met. A review of literature fails to identify cases of hemophagocytic lymphohistiocytosis associated with respiratory syncytial virus in immunocompetent adults. This case report provides further insight on RSV as a possible etiologic agent associated with HLH and the importance of early recognition of this fatal disorder in RSV-positive patients who show unpredictable clinical decompensation.

Primary plasma cell leukemia: A case report and review of the literature.

Due to the rarity and fulminant nature of the condition, there are limited data driving dialogue for optimal treatment strategies for plasma cell leukemia (PCL). Additionally, the current diagnostic definition of PCL has not been prospectively studied which may result in delays to initiating early aggressive treatment due to underdiagnosis.

Successful Treatment of Hepatitis C Virus by Ledipasvir/Sofosbuvir in a Cirrhotic Patient with Sickle Cell Disease and Thalassemia Minor.

Around 8% of patients diagnosed with sickle cell disease (SCD) are hepatitis C virus (HCV) carriers. Previously, HCV treatment was seldom considered in SCD patients, as the ribavirin-induced hemolysis and interferon-induced cytopenias could lead to more profound anemia. Nowadays, several oral direct-acting antiviral drugs have been developed and approved by the FDA for hepatitis C treatment. While direct-acting antivirals mitigate many of these risks, their safety and efficacy in SCD patients remains insufficiently explored. Here, we report on successfully treating HCV with ledipasvir/sofosbuvir in a compensated cirrhotic patient with SCD and thalassemia minor.

Emerging role of immunotherapy in precursor B-cell acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia that carries poor prognosis in adults especially in the setting of high risk cytogenetics and relapsed/refractory (R/R) disease. Advancements in immunotherapy have led to the development of several monoclonal antibodies (MoAbs) and chimeric antigen receptor (CAR) T cells that are capable of targeting certain surface antigens on leukemic cells, resulting in their destruction. Areas covered: This article reviews the mechanism of action, outcomes of various trials, and adverse effects of MoAbs and CAR-T cells used in the treatment of precursor B-cell ALL. Expert commentary: Some of the immunotherapeutic agents that have been approved for the treatment of R/R precursor B-cell ALL have shown superior efficacy and safety profile compared to chemotherapy in advanced disease. Several trials are now being conducted to evaluate the role of certain MoAbs in combination with chemotherapy in the treatment of B-cell ALL. Additionally, their use in the frontline setting with more favorable host characteristics may also result in superior outcomes compared to the current standard of care.

Eosinophilia as the presenting sign in pancreatic cancer: an extremely rare occurrence.

A case of pancreatic adenocarcinoma diagnosed following work up for eosinophilia is reported. A 68-year-old female was referred to our Hematology clinic for an absolute eosinophil count of 1869 per microliter. No allergic signs or symptoms were reported. Laboratory studies for parasitic infestations autoimmune disease and collagen vascular disease were negative. Computed tomography of the abdomen revealed a mass in the neck of the pancreas with fine needle aspiration biopsy consistent with adenocarcinoma. The patient received one cycle of modified FOLFIRINOX with complete resolution of the eosinophilia. There are rare case reports of tumor-associated blood eosinophilia in solid malignancies. The finding may be indicative of rapid disease progression and poor prognosis. Our case is the third in published English literature with eosinophilia being the initial finding in pancreatic cancer.

Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

The treatment landscape for multiple myeloma (MM) is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy with other treatment modalities in MM therapy. As our discovery of these emerging therapies progresses, so too does our need to reshape our knowledge on knowing how to apply them. This review highlights some of the recent landmark changes in MM management with specific emphasis on salvage drugs available for relapsed and refractory MM and also discusses some of the upcoming cutting-edge therapies that are currently in various stages of clinical development.