Oncologist
SCOPUS (1996-2023)SCIE-ISI
1549-490X
1083-7159
Mỹ
Cơ quản chủ quản: Oxford University Press , OXFORD UNIV PRESS
Các bài báo tiêu biểu
After completing this course, the reader will be able to: Discuss the evolving changes in the following cancer-related measures: median age at diagnosis, incidence rate, death rate, lifetime risk, survival, and prevalence.Explain important concepts affecting occurrence of multiple primary cancers at various cancer sites.Describe the impact of the growing and aging population on the future number of cancer cases by age at diagnosis.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Fatigue is one of the most common and debilitating symptoms experienced by patients with cancer. Cancer-related fatigue (CRF) is characterized by feelings of tiredness, weakness, and lack of energy, and is distinct from the “normal” drowsiness experienced by healthy individuals in that it is not relieved by rest or sleep. It occurs both as a consequence of the cancer itself and as a side effect of cancer treatment, although the precise underlying pathophysiology is largely unknown. CRF may be an early symptom of malignant disease and is reported by as many as 40% of patients at diagnosis. Virtually all patients expect fatigue from cancer therapy. Up to 90% of patients treated with radiation and up to 80% of those treated with chemotherapy experience fatigue. CRF continues for months and even years ollowing completion of treatment in approximately one third of the patients with cancer. The impact of CRF on a patient's quality of life (QoL), particularly in relation to physical functioning and the ability to perform activities of daily living, is both profound and pervasive. In addition, CRF is associated with considerable psychological distress and can impose a significant financial burden by limiting a patient's ability to work. These effects can extend to caregivers and family members, who may also have to reduce their working capacity in order to provide additional care for a patient with CRF. This paper examines the prevalence of CRF and explores the impact of this distressing symptom on patients' functioning and QoL.
Disclosure of potential conflicts of interest is found at the end of this article.
After completing this course, the reader will be able to:
Explain the effect of hypoxia on resistance to treatment. Describe the causes of tumor hypoxia. Characterize cellular response to hypoxia.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Hypoxia is a characteristic feature of locally advanced solid tumors resulting from an imbalance between oxygen (O2) supply and consumption. Major causative factors of tumor hypoxia are abnormal structure and function of the microvessels supplying the tumor, increased diffusion distances between the nutritive blood vessels and the tumor cells, and reduced O2 transport capacity of the blood due to the presence of disease- or treatment-related anemia. Tumor hypoxia is a therapeutic concern since it can reduce the effectiveness of radiotherapy, some O2-dependent cytotoxic agents, and photodynamic therapy. Tumor hypoxia can also negatively impact therapeutic outcome by inducing changes in the proteome and genome of neoplastic cells that further survival and malignant progression by enabling the cells to overcome nutritive deprivation or to escape their hostile environment. The selection and clonal expansion of these favorably altered cells further aggravate tumor hypoxia and support a vicious circle of increasing hypoxia and malignant progression while concurrently promoting the development of more treatment-resistant disease. This pattern of malignant progression, coupled with the demonstration of a relationship between falling hemoglobin level and worsening tumor oxygenation, highlights the need for effective treatment of anemia as one approach for correcting anemic hypoxia in tumors, and in so doing, possibly improving therapeutic response.
After completing this course, the reader will be able to: Identify trials that have demonstrated a survival benefit with a modern chemotherapeutic agent or regimen in MBC.Summarize recent findings of randomized trials showing survival benefits with targeted therapy–chemotherapy combinations in MBC.Discuss quality-of-life findings and their implications in clinical practice.
Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com
Metastatic breast cancer (MBC) remains essentially incurable, and goals of therapy include the palliation of symptoms, delay of disease progression, and prolongation of overall survival time without negatively impacting quality of life. Anthracycline and taxane-based therapies have traditionally shown the highest degree of activity in MBC. Though numerous randomized clinical trials have shown improvements in overall response rates, few have found clear survival benefits. In recent years, however, there has been a small but growing series of clinical trials demonstrating modest, but meaningful survival advantages in metastatic disease. A common feature in many of these trials has been the use of a taxane, and more recently, a taxane combined with an antimetabolite. In addition, the development of targeted biologic agents active against MBC, such as trastuzumab and bevacizumab, has demonstrated great potential for enhancing the effects of chemotherapy and producing meaningful survival improvements. The role of the taxanes, antimetabolites, and biologics in extending survival in MBC is discussed.
After completing this course, the reader will be able to: Discuss and compare currently approved drugs for treatment of glioblastoma multiforme (GBM) and explain the advantages of bevacizumab for GBM treatment.Debate the use of response rate as an endpoint for GBM treatment with bevacizumab.Differentiate between accelerated and regular drug approval by the Food and Drug Administration.
This article is available for continuing medical education credit at CME.TheOncologist.com.
On May 5, 2009, the U.S. Food and Drug Administration granted accelerated approval to bevacizumab injection (Avastin®; Genentech, Inc., South San Francisco, CA) as a single agent for patients with glioblastoma multiforme (GBM) with progressive disease following prior therapy. The approval was based on durable objective responses (independent radiologic review with stable or decreasing corticosteroid use). Two trials evaluating bevacizumab, 10 mg/kg by i.v. infusion every 2 weeks, were submitted. One trial also randomized patients to bevacizumab plus irinotecan treatment. All patients had received prior surgery, radiotherapy, and temozolomide. Patients with active brain hemorrhage were excluded. One trial enrolled 78 independently confirmed GBM patients. Partial responses were observed in 25.9% (95% confidence interval [CI], 17.0%–36.1%) of the patients. The median response duration was 4.2 months (95% CI, 3.0–5.7 months). The second trial enrolled 56 GBM patients. Partial responses were observed in 19.6% (95% CI, 10.9%–31.3%) of the patients. The median response duration was 3.9 months (95% CI, 2.4–17.4 months). Safety data were provided for the first study. The most frequently reported bevacizumab adverse events of any grade were infection, fatigue, headache, hypertension, epistaxis, and diarrhea. Grade 3–5 bevacizumab-related adverse events included bleeding/hemorrhage, central nervous system (CNS) hemorrhage, hypertension, venous and arterial thromboembolic events, wound-healing complications, proteinuria, gastrointestinal perforation, and reversible posterior leukoencephalopathy. The attribution of certain adverse events (e.g., CNS hemorrhage, wound-healing complications, and thromboembolic events) to either bevacizumab, underlying disease, or both could not be determined because of the single-arm, noncomparative study design.
After completing this course, the reader will be able to:
Explain the biology of angiogenesis. Identify the role of VEGF in normal and tumor angiogenesis. Describe the key ways in which VEGF has been targeted in cancer therapy.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit atCME.TheOncologist.com
The development of a vascular supply is a critical factor in the growth and metastatic spread of malignant tumors. Of the multitude of growth factors that regulate physiological and pathological angiogenesis, vascular endothelial growth factor (VEGF) is believed to be the most important. There is evidence that overexpression of VEGF is correlated with an adverse prognosis, at least in some tumors. Tumor-expressed VEGF is particularly attractive as a target for anticancer therapy because its angiogenesis-promoting activity is at the level of the endothelial cell and, compared with agents that directly target tumor cells, tumor penetration is less critical for VEGF inhibitors. Moreover, recent work has shown that inhibiting tumor angiogenesis increases the effectiveness of coadministered chemotherapy and radiotherapy. This suggests that drugs that target VEGF or its receptors can be combined with traditional treatment modalities to ensure maximum effectiveness. A variety of agents aimed at blocking VEGF or its receptor-signaling system are currently being developed for the treatment of cancer. Of these, bevacizumab, a humanized monoclonal antibody directed at VEGF, is the most advanced in clinical development and has shown promising results in clinical trials.
The incidence of melanoma is increasing worldwide, and the prognosis for patients with high-risk or advanced metastatic melanoma remains poor despite advances in the field. Standard treatment for patients with thick (≥2.0 mm) primary melanoma with or without regional metastases to lymph nodes is surgery followed by adjuvant therapy or clinical trial enrollment. Adjuvant therapy with interferon-α and cancer vaccines is discussed in detail. Patients who progress to stage IV metastatic melanoma have a median survival of ≤1 year. Standard treatment with chemotherapy yields low response rates, of which few are durable. Cytokine therapy with IL-2 achieves durable benefits in a greater fraction, but it is accompanied by severe toxicities that require the patient to be hospitalized for support during treatment. A systematic literature review of treatments for advanced, metastatic disease was conducted to present the success of current treatments and the promise of those still in clinical development that may yield incremental improvements in the treatment of advanced, metastatic melanoma.
The growth of human tumors and development of metastases depend on the de novo formation of blood vessels. The formation of new blood vessels is tightly regulated by specific growth factors that target receptor tyrosine kinases (RTKs). Vascular endothelial growth factor (VEGF) and the Flk-1/KDR RTK have been implicated as the key endothelial cell-specific factor signaling pathway required for pathological angiogenesis, including tumor neovascularization. Inhibition of the VEGF tyrosine kinase signaling pathway blocks new blood vessel formation in growing tumors, leading to stasis or regression of tumor growth. Advances in understanding the biology of angiogenesis have led to the development of several therapeutic modalities for the inhibition of the VEGF tyrosine kinase signaling pathway. A number of these modalities are under investigation in clinical studies to evaluate their potential to treat human cancers.
After completing this course, the reader will be able to: Describe the presentation, differential diagnosis, and prognosis for patients with Ewing's sarcoma.Explain the principles of multidisciplinary management of Ewing's sarcoma.Discuss the late effects of the therapy for Ewing's sarcoma.
Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com
Ewing's sarcoma is the second most frequent primary bone cancer, with approximately 225 new cases diagnosed each year in patients less than 20 years of age in North America. It is one of the pediatric small round blue cell tumors, characterized by strong membrane expression of CD99 in a chain-mail pattern and negativity for lymphoid (CD45), rhabdomyosarcoma (myogenin, desmin, actin) and neuroblastoma (neurofilament protein) markers. Pathognomonic translocations involving the ews gene on chromosome 22 and an ets-type gene, most commonly the fli1 gene on chromosome 11, are implicated in the great majority of cases. Clinical presentation is usually dominated by local bone pain and a mass. Imaging reveals a technetium pyrophosphate avid lesion that, on plain radiograph, is destructive, diaphyseal and classically causes layered periosteal calcification. Magnetic resonance best defines the extent of the lesion. Biopsy should be undertaken by an experienced orthopedic oncologist. Approximately three quarters of patients have initially localized disease. About two thirds survive disease-free. Management, preferably at a specialist center with a multi-disciplinary team, includes both local control—either surgery, radiation or a combination—and systemic chemotherapy. Chemotherapy includes cyclic combinations, incorporating vincristine, doxorubicin, cyclophosphamide, etoposide, ifosfamide and occasionally actinomycin D. Topotecan in combination with cyclophosphamide has shown preliminary activity. Patients with initially metastatic disease fare less well, with about one quarter surviving. Studies incorporating intensive therapy followed by stem cell infusion show no clear benefit. New approaches include anti-angiogenic therapy, particularly since vascular endothelial growth factor is an apparent downstream target of the ews-fli1 oncogene.
After completing this course, the reader will be able to: List the multiple cell death pathways that are activated in response to chemotherapeutic agents.Identify signaling molecules involved and morphological changes that occur in the different types of cell death pathways.Describe mechanisms targeted by novel chemotherapeutic agents.
Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com
For several decades, apoptosis has taken center stage as the principal mechanism of programmed cell death in mammalian tissues. It also has been increasingly noted that conventional chemotherapeutic agents not only elicit apoptosis but other forms of nonapoptotic death such as necrosis, autophagy, mitotic catastrophe, and senescence. This review presents background on the signaling pathways involved in the different cell death outcomes. A re-examination of what we know about chemotherapy-induced death is vitally important in light of new understanding of nonapoptotic cell death signaling pathways. If we can precisely activate or inhibit molecules that mediate the diversity of cell death outcomes, perhaps we can succeed in more effective and less toxic chemotherapeutic regimens.