Cellular Components Contributing to the Development of Venous Thrombosis in Patients with Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer and has a poor prognosis. Patients with PDAC are at high risk of developing thromboembolic events, which is a leading cause of morbidity and mortality following cancer progression. Plasma-derived coagulation is the most studied process in cancer-associated thrombosis. Other blood components, such as platelets, red blood cells, and white blood cells, have been gaining less attention. This narrative review addresses the literature on the role of cellular components in the development of venous thromboembolism (VTE) in patients with PDAC. Blood cells seem to play an important role in the development of VTE. Altered blood cell counts, i.e., leukocytosis, thrombocytosis, and anemia, have been found to associate with VTE risk. Tumor-related activation of leukocytes leads to the release of tissue factor-expressing microvesicles and the formation of neutrophil extracellular traps, initiating coagulation and forming a scaffold for thrombi. Tissue factor-expressing microvesicles are also thought to be released by PDAC cells. PDAC cells have been shown to stimulate platelet activation and aggregation, proposedly via the secretion of podoplanin and mucins. Hypofibrinolysis, partially explained by increased plasminogen activator inhibitor-1 activity, is observed in PDAC. In short, PDAC-associated hypercoagulability is a complex and multifactorial process. A better understanding of cellular contributions to hypercoagulability might lead to the improvement of diagnostic tests to identify PDAC patients at highest risk of VTE.

Evolving data on cardiovascular complications in cancer.

Cancer and cardiovascular disease are leading causes of mortality and morbidity worldwide. Scientific studies show that patients with cancer are at increased risk of developing cardiovascular events, leading to the novel cardio-oncology research field. Growing evidence suggests that cancer and cardiovascular disease are not separate entities but are connected through shared risk factors, pathological mechanisms, and genetic predispositions. Moreover, anticancer therapies such as radiotherapy have been known to further increase the cardiovascular risk in patients with cancer. Due to the significant advances in oncological diagnostics and therapy, the number of cancer survivors has been growing substantially. Nowadays, the majority of patients with cancer dies from non-cancer causes. Cardiovascular disease substantially contributes to mortality and morbidity in cancer survivors. For some cancers, such as breast, prostate, endometrial and thyroid cancer, about half of the patients dies from cardiovascular disease. This raises an urge for effective strategies in preventing and treating cardiovascular events in patients living with and surviving cancer. In this review, we address the evolving data on cardiovascular disease in patients with cancer, with a special focus on atherothrombotic manifestations including myocardial infarction and ischemic stroke.

Dynamics of eligibility criteria for central nervous system metastases in non-small cell lung cancer randomized clinical trials over time: A systematic review.

Although central nervous system (CNS) metastases frequently occur in patients with non-small cell lung cancer (NSCLC), historically these patients have been excluded from clinical trials. However, due to improving NSCLC prognosis, time to develop CNS metastases increases and information on CNS efficacy of systemic treatment is important. We performed a systematic PubMed review (2000-2020) to describe CNS related eligibility and screening criteria over time. Randomized phase III, and for tyrosine kinase inhibitors (TKIs) also randomized phase II trials enrolling advanced/metastatic NSCLC patients were included. 256/1195 trials were included. In 71 %, CNS metastases were eligible, but in only 3% regardless of symptoms/treatment. Only 37 % required baseline CNS screening (most often TKI and immunotherapy trials), without significant increase over time. A CNS endpoint was pre-specified in 4%. CONCLUSION: CNS screening and eligibility criteria are heterogenous across trials, and CNS related endpoints are rare. These criteria and endpoints should be improved and harmonized.