Pulmonary blastoma: a comprehensive overview of a rare entity

Introduction: Pulmonary blastoma is a rare malignancy, accounting for less than 0.5% of primary lung tumors. It belongs to the group of pulmonary sarcomatoid carcinomas, and it is typically characterized by a biphasic pattern of an epithelial and a mesenchymal component. Only a few hundred cases have been reported worldwide. The aim of this study is to review and critically assess the literature regarding pulmonary blastoma.Material and methods: A narrative literature review of PubMed database from the inception of the database up to January 2021, limited to the English language, was conducted, using combinations of the following keywords: “pulmonary blastoma”, “biphasic pulmonary blastoma”, “sarcomatoid carcinoma”.Results: Pulmonary blastoma is composed of an epithelial and a mesenchymal malignant component. Regarding pathogenesis, the origin of the biphasic cell population remains elusive. Characteristic immunohistochemical stains are supportive of diagnosis.Clinically, the symptomatology is non-specific, while 40% of the cases are asymptomatic. It is diagnosed at a younger agecompared to other types of lung cancer, and it is often non-metastatic at diagnosis allowing for surgical treatment. Data on management and survival are scarce and mainly come from isolated cases. Advances on targeted therapy may provide novel treatment options. Given the rarity of the cases, multicenter collaboration is needed in order to establish therapeutic guidelines

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist

Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options

The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated the success story of targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy in patients with NSCLC with sensitizing EGFR mutations, as second-line therapy in patients who present the resistance-associated mutation T790M after treatment with previous EGFR-TKIs, and as adjuvant therapy for patients with early stage resected NSCLC, harboring EGFR mutations. Despite durable responses in patients with advanced NSCLC, resistance to osimertinib, similar to other targeted therapies, inevitably develops. Understanding the mechanisms of resistance, including both EGFR-dependent and -independent molecular pathways, as well as their therapeutic potential, represents an unmet need in thoracic oncology. Interestingly, differential resistance mechanisms develop when osimertinib is administered in a first-line versus second-line setting, indicating the importance of selection pressure and clonal evolution of tumor cells. Standard therapeutic approaches after progression to osimertinib include other targeted therapies, when a targetable genetic alteration is detected, and cytotoxic chemotherapy with or without antiangiogenic and immunotherapeutic agents. Deciphering the when and how to use immunotherapeutic agents in EGFR-positive NSCLC is a current challenge in clinical lung cancer research. Emerging treatment options after progression to osimertinib involve combinations of different therapeutic approaches and novel EGFR-TKI inhibitors. Research should also be focused on the standardization of liquid biopsies in order to facilitate the monitoring of molecular alterations after progression to osimertinib

Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options

The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated the success story of targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy in patients with NSCLC with sensitizing EGFR mutations, as second-line therapy in patients who present the resistance-associated mutation T790M after treatment with previous EGFR-TKIs, and as adjuvant therapy for patients with early stage resected NSCLC, harboring EGFR mutations. Despite durable responses in patients with advanced NSCLC, resistance to osimertinib, similar to other targeted therapies, inevitably develops. Understanding the mechanisms of resistance, including both EGFR-dependent and -independent molecular pathways, as well as their therapeutic potential, represents an unmet need in thoracic oncology. Interestingly, differential resistance mechanisms develop when osimertinib is administered in a first-line versus second-line setting, indicating the importance of selection pressure and clonal evolution of tumor cells. Standard therapeutic approaches after progression to osimertinib include other targeted therapies, when a targetable genetic alteration is detected, and cytotoxic chemotherapy with or without antiangiogenic and immunotherapeutic agents. Deciphering the when and how to use immunotherapeutic agents in EGFR-positive NSCLC is a current challenge in clinical lung cancer research. Emerging treatment options after progression to osimertinib involve combinations of different therapeutic approaches and novel EGFR-TKI inhibitors. Research should also be focused on the standardization of liquid biopsies in order to facilitate the monitoring of molecular alterations after progression to osimertinib

Immunotherapy for pancreatic cancer

Pancreatic cancer is among the most lethal malignancies resistant to conventional therapies. The vast majority of patients is diagnosed with advanced/metastatic disease and consequently has grim prognosis. Despite the available options with nab-paclitaxel and gemcitabine or 5-fluorouracil/leucovorin/oxaliplatin, chemotherapy offers a modest survival benefit. Targeted therapy in combination with chemotherapy has not shown significant improvement in treatment outcomes. The urgent need for new therapies has turned the spotlights on immunotherapy. Immunotherapy in pancreatic cancer recruits and activates T cells which recognize tumor-specific antigens. Preclinical models have demonstrated that chemotherapy or targeted therapy works synergistically with immunotherapy. A growing body of evidence has already been gathered regarding the efficacy of checkpoint inhibitors, vaccines, adoptive T cell therapy, monoclonal antibodies, and cytokines in patients with pancreatic cancer. Many ongoing trials are aiming to identify treatments which could combine efficacy with limited toxicity. In this article, we review the available data concerning multiple aspects of immunotherapy in pancreatic cancer

Adhesion molecules in lung cancer: Implications in the pathogenesis and management

Growth and metastasis of lung cancer requires a sequence of events, which alter the ability of neoplastic cells to adhere to themselves, to normal surrounding cells, or to the extracellular matrix. Interactions between cells are primarily mediated by four types of structures in the plasma membrane: gap junctions, tight junctions, desmosomes, and adherence junctions. We have reviewed the existing data on the implication of adhesion molecules in the pathogenesis of lung cancer, as well as the application of certain adhesion molecules as potential surrogate markers in lung cancer patients

A case of trastuzumab-induced dermatomyositis

Human epidermal growth factor receptor 2 (HER-2) is a checkpoint, controlling cell proliferation and differentiation. Trastuzumab, a humanized monoclonal antibody directed against HER-2, is nowadays standard treatment for breast cancer patients whose tumors express HER-2. It is generally well tolerated, with a small number of patients developing mild adverse reactions. Dermatomyositis is a rare adverse event of trastuzumab therapy not well described in the literature. We herein present a case of a patient treated for hormone-sensitive invasive ductal carcinoma, who presented with symptoms of proximal muscle weakness, arthralgias, skin rash, and generalized fatigue. The symptoms started after the sixth cycle of trastuzumab and progressively deteriorated. The patient's medical and family history was unremarkable. Disease progression as a possible cause of dermatomyositis had been ruled out, and laboratory evaluation revealed moderate elevation of serum muscle proteins and acute-phase reactants. Trastuzumab treatment was discontinued, and 3 months later, the patient was free of symptoms without any further intervention

The Emerging Role of Tyrosine Kinase Inhibitors in Ovarian Cancer Treatment: A Systematic Review

The present systematic review summarizes current evidence regarding the mechanisms of action, the efficacy, and the adverse effects of tyrosine kinase inhibitors (TKIs) in ovarian cancer patients. Phase II and III clinical trials were sought in the PubMed database and in the Clinical Trials.gov registry through September 30, 2015. Seventy-five clinical trials regarding TKIs targeting mainly vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, and sarcoma tyrosine kinase (Src) were yielded. The most promising results were noted with cediranib, nintedanib, and pazopanib. However, drawing universal conclusions about the potential integration of TKIs in ovarian cancer therapy remains elusive. Furthermore, emerging challenges and directions for the future research are critically discussed

Management and Outcomes in Metaplastic Breast Cancer

Metaplastic breast cancer (MBC) constitutes a rare clinical entity with special clinicopathologic, immunohistochemical, and molecular features. Resistance to systemic therapies, whether chemotherapy or hormonal therapy, is among its main characteristics, which in turn explains the poor prognosis and renders its management a challenge. Thus, the scope of the present review is to discuss the current therapeutic strategies for MBC in clinical practice and the corresponding outcomes and to suggest possible directions for future research. Potential novel targeted therapies could provide a hope for better outcomes but limited data are available owing to the rarity of MBC. As knowledge accumulates on the pathogenesis and genetic characteristics of MBC, emphasis should be given to the implementation of more targeted treatments, which will allow more efficient and individualized management of the disease. (C) 2016 Elsevier Inc. All rights reserved