The oncologist
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Anemia in cancer patients can be treated with transfusions, and 15% of patients with solid tumors are being treated by transfusions. Different cutoff values are used for transfusions, depending on clinical symptoms and patient characteristics, with a hemoglobin (Hb) level of <9 g/dL most commonly used. After the administration of one unit of red blood cells (RBC), the Hb rises with 1 g/dL, and the life span of transfused RBC is 100-110 days. ⋯ RBC transfusions have been related to increased risk of the development of non-Hodgkin lymphoma and chronic lymphocytic leukemia, and are related to a worse treatment outcome in selected cancers. In addition, the cost of a transfusion for the patient and society is around 300-500 euros per unit transfused. RBC transfusions should be used carefully to correct anemia in patients with cancer.
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The objective of this paper is to introduce clinicians and health care professionals to the concept of patient blood management (PBM) and to explain the difference between PBM and the concept of "appropriate use" of blood products. The five reasons why modern health systems need to shift from product-focused transfusion practice to PBM are also presented. These are: the aging population with a leveraged demand for blood products opposed to a shrinking donor base; the growing awareness that transfusion is a complex service involving many different cost centers within a hospital and representing a multiple of the blood product cost; the continuous effort to protect blood pools from known, new, or re-emerging pathogens while facing uncertainty over their potentially long silent carrier states; the emerging evidence that transfusion is an independent risk factor for adverse outcomes; and finally, a lack of evidence for benefit of transfusion for the vast majority of recipients.
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The possibility of targeting tumor angiogenesis was postulated almost 40 years ago. The vascular endothelial growth factor (VEGF) family and its receptors have since been characterized and extensively studied. VEGF overexpression is a common finding in solid tumors, including esophagogastric cancer, and frequently correlates with poor prognosis. ⋯ Evaluation of bevacizumab in the neoadjuvant and perioperative settings continues, hypothesizing that a higher response rate will translate into longer survival in patients with operable disease. Despite extensive research, the discovery of a reliable predictive biomarker for antiangiogenic therapy continues to elude the scientific and oncology communities, and mechanisms of primary and acquired resistance are incompletely understood. We are therefore currently unable to personalize antiangiogenic therapy for established indications, or use molecular selection for clinical trials evaluating novel indications.
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The phosphoinositide-3 kinase (PI3K) pathway has been identified as an important target in breast cancer research for a number of years, but is new to most clinicians responsible for the daily challenges of breast cancer management. In fact, the PI3K pathway is probably one of the most important pathways in cancer metabolism and growth. Mutations in the PI3K pathway are frequent in breast cancer, causing resistance to human epidermal growth factor receptor 2-targeted agents and, possibly, to hormonal agents as well. ⋯ Multiple PI3K inhibitors are currently under development, including pure PI3K inhibitors, compounds that block both PI3K and mTOR (dual inhibitors), pure catalytic mTOR inhibitors, and inhibitors that block Akt. It is likely that these agents will have to be given in combination with other signal inhibitors because anti-mTOR agents and PI3K inhibitors may result in the activation of compensatory feedback loops that would in turn result in decreased efficacy. This article reviews current data related to the PI3K pathway, its role in breast cancer, the frequency with which PI3K is aberrant in breast cancer, and the potential clinical implications of using agents that target the PI3K pathway.