Talimogene laherparepvec (T-VEC) and Emerging Intralesional Immunotherapies for Metastatic Melanoma: A Review.

Purpose Of Review: As the incidence of cutaneous melanoma continues to rise worldwide, its heterogeneous presentation proves challenging for managing and preventing relapse.

Recent Findings: While surgery remains a mainstay in staging and treatment of locoregional metastatic melanoma, intralesional therapies have emerged as a new tool to treat unresectable in-transit and nodal metastases and reduce the risk of relapse through immunomodulatory mechanisms. In this review, we will provide an overview of intralesional therapies for melanoma with a particular focus on talimogene laherparepvec (T-VEC) and its future uses.

Sex disparities in outcomes among hospitalizations for heart failure.

This study investigated sex differences in clinical characteristics and in-hospital outcomes of heart failure (HF) hospitalizations using the National Inpatient Sample data, 2016-2019. HF hospitalizations ≥ 41 years of age were included and stratified by sex. Study outcomes were in-hospital mortality, prolonged length of stay, mechanical ventilation, mechanical circulatory support, vasopressor use, and disposition other than home.

Prevalence and outcomes of atrial fibrillation in patients hospitalized with COVID-19.

Objective: Atrial fibrillation (AF) is a common arrhythmia in patients at high cardiovascular risk. COVID-19 patients with underlying cardiovascular disease are at increased risk of poor clinical outcomes. In this study, we aimed to determine hospital outcomes among patients admitted with AF and COVID-19 infection.

Association between high risk of obstructive sleep apnea and inflammatory markers in a population sample of young and middle-aged adults in the Miami Heart Study.

Study Objectives: There are limited data depicting the association between high risk of obstructive sleep apnea (OSA) and the levels of inflammatory markers in a population-based sample free from cardiovascular disease (CVD). In a large US cohort enriched with a Hispanic population and free of CVD, we aimed to assess the association between high risk of OSA and inflammatory markers.

Methods: We analyzed data for 2,359 clinical CVD-free participants from the Miami Heart Study, aged 40-65 years (May 2015-September 2018).

A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR).

Recurrent high-grade gliomas (rHGGs) have a dismal prognosis, where the maximum tolerated dose (MTD) of IV terameprocol (5 days/month), a transcriptional inhibitor of specificity protein 1 (Sp1)-regulated proteins, is 1,700 mg/day with median area under the plasma concentration-time curve (AUC) of 31.3 μg∗h/mL. Given potentially increased efficacy with sustained systemic exposure and challenging logistics of daily IV therapy, here we investigate oral terameprocol for rHGGs in a multicenter, phase 1 trial (GATOR).

Impact of tissue-agnostic approvals on management of primary brain tumors.

Novel tissue-agnostic therapeutics targeting driver mutations in tumor cells have been recently approved by FDA, driven by basket trials that have demonstrated their efficacy and safety across diverse tumor histology. However, the relative rarity of primary brain tumors (PBTs) has limited their representation in early trials of tissue-agnostic medications. Thus, consensus continues to evolve regarding utility of tissue-agnostic medications in routine practice for PBTs, a diverse group of neoplasms characterized by limited treatment options and unfavorable prognoses.

Measured Steps: Navigating the Path of Oligoprogressive Lung Cancer with Targeted and Immunotherapies.

Purpose Of Review: This review discusses the definitions, treatment modalities, management, future directions, and ongoing clinical trials of oligoprogressive disease in oncogene-driven and non-oncogene-driven NSCLC.

Recent Findings: During the last decades, diagnostic and treatment modalities for oligometastatic NSCLC have advanced significantly, leading to improved survival. Additionally, our understanding of the tumor biology of oligoprogressive disease has expanded.

Management of Brain Metastases: A Review of Novel Therapies.

Brain metastases (BMs) represent the most common intracranial tumors in adults, and most commonly originate from lung, followed by breast, melanoma, kidney, and colorectal cancer. Management of BM is individualized based on the size and number of brain metastases, the extent of extracranial disease, the primary tumor subtype, neurological symptoms, and prior lines of therapy. Until recently, treatment strategies were limited to local therapies, like surgical resection and radiotherapy, the latter in the form of whole-brain radiotherapy or stereotactic radiosurgery.

Bispecific Antibodies in Lung Cancer: A State-of-the-Art Review.

Bispecific antibodies have emerged as a promising class of therapeutics in the field of oncology, offering an innovative approach to target cancer cells while sparing healthy tissues. These antibodies are designed to bind two different antigens, enabling them to bridge immune cells with cancer cells, resulting in enhanced tumor cell killing and improved treatment responses. This review article summarizes the current landscape of bispecific antibodies in lung cancer, including their mechanisms of action, clinical development, and potential applications in other solid tumor malignancies.

Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients.

Purpose: Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently.

Endoglin inhibitor TRC105 with or without bevacizumab for bevacizumab-refractory glioblastoma (ENDOT): a multicenter phase II trial.

Background: Glioblastoma (GBM), the most lethal primary brain tumor, has limited treatment options upon recurrence after chemoradiation and bevacizumab. TRC105 (carotuximab), a chimeric anti-endoglin (CD105) antibody, inhibits angiogenesis and potentiates activity of VEGF inhibitor bevacizumab in preclinical models. This study sought to assess safety, pharmacokinetics, and efficacy of TRC105 for bevacizumab-refractory GBM.

Atherosclerotic plaque in individuals without known cardiovascular disease but with established obstructive sleep apnea and at high risk of obstructive sleep apnea.

Objectives: In a large U.S. cohort free of CVD evaluated by coronary computed CT angiography, we aimed to assess the association between established / high risk of Obstructive Sleep Apnea (OSA) and coronary plaque.

The Utility of Bronchoscopy in Hydralazine-Induced ANCA-Associated Vasculitis.

Hydralazine is a vasodilator used for the management of hypertension, heart failure, and hypertensive emergencies in pregnancy. It has been implicated in the causation of drug-induced lupus erythematosus (DLE) and rarely with ANCA-associated vasculitis (AAV), which may present as a pulmonary-renal syndrome and be rapidly fatal. Herein, we describe a case of hydralazine-associated AAV presenting as acute kidney injury with the use of early bronchoalveolar lavage (BAL) with serial aliquots to aid with diagnosis.

DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets.

Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I-IV (now 1-4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as histone methylation, DNA methylation, and histone acetylation, which are increasingly being used for the classification of low-grade gliomas. This review describes the current understanding of the role of DNA methylation, demethylation, and histone modification in pathogenesis, clinical behavior, and outcomes of brain tumors, in particular of low-grade gliomas.

Key Clinical Principles in the Management of Glioblastoma.

Glioblastoma is the most common and aggressive primary brain tumor in the adult population and leads to considerable morbidity and mortality. It has a dismal prognosis with average survival of 15-18 months, and the current standard-of-care treatment paradigm includes maximal surgical resection and postoperative concurrent chemoradiotherapy and maintenance chemotherapy, with consideration of Tumor Treating Fields. There is a major emphasis to enroll patients onto ongoing clinical trials to further improve treatment outcomes, given the aggressive nature of the disease course and poor patient survival.

Novel Therapeutic Approaches in Neoplastic Meningitis.

Central nervous system (CNS) metastasis from systemic cancers can involve the brain parenchyma, leptomeninges, or the dura. Neoplastic meningitis (NM), also known by different terms, including leptomeningeal carcinomatosis and carcinomatous meningitis, occurs due to solid tumors and hematologic malignancies and is associated with a poor prognosis. The current management paradigm entails a multimodal approach focused on palliation with surgery, radiation, and chemotherapy, which may be administered systemically or directly into the cerebrospinal fluid (CSF).

Outcomes and Trends of Endoscopic Bariatric Therapies (EBT) Among Minority Populations.

Introduction: Endoscopic bariatric therapies (EBT) have emerged as effective options for weight loss. While the benefits of EBT have been documented, data regarding such therapies among minority populations remains scant. We aim to investigate EBT trends and outcomes in minority populations.

Update on the Management of Brain Metastasis.

Brain metastases occur in almost one-third of adult patients with solid tumor malignancies and lead to considerable patient morbidity and mortality. The rising incidence of brain metastases has been ascribed to the development of better imaging and screening techniques and the formulation of better systemic therapies. Until recently, the multimodal management of brain metastases focused primarily on the utilization of neurosurgical techniques, with varying combinations of whole-brain radiation therapy and stereotactic radio-surgical procedures.

Prior Tonsillectomy and the Risk of Breast Cancer in Females: A Systematic Review and Meta-analysis.

Background: Exposure to recurrent infections in childhood was linked to an increased risk of cancer in adulthood. There is also evidence that a history of tonsillectomy, a procedure often performed in children with recurrent infections, is linked to an increased risk of leukemia and Hodgkin lymphoma. Tonsillectomy could be directly associated with cancer risk, or it could be a proxy for another risk factor such as recurrent infections and chronic inflammation.