With the advent of a new generation of PET scanners that have introduced whole-body PET to the clinical setting, there is now more interest in developing protocols for the evaluation of both intracranial and somatic cancers. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumors, head and neck tumors, primary and metastatic brain tumors, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. A summary of current clinical applications of PET in oncology is presented with special attention to colorectal, lung, and intracranial neoplasms since the majority of clinical trials have focused on these cancers. A variety of radiopharmaceuticals are described that are currently included in clinical tumor-imaging protocols, including metabolic substrates such as fluorine-18-fluorodeoxyglucose and carbon-11-methionine, and analogs of chemotherapeutic agents such as fluorine-18-fluorouracil and fluoroestradiol. An attempt is also made to include examples of clinical trials that demonstrate response to therapeutic intervention. The increasing number of oncologic PET studies reflects the growing interest in functional imaging in oncology.
UNLABELLED: The availability of accurately aligned, whole-body anatomical (CT) and functional (PET) images could have a significant impact on diagnosing and staging malignant disease and on identifying and localizing metastases. Computer algorithms to align CT and PET images acquired on different scanners are generally successful for the brain, whereas image alignment in other regions of the body is more problematic. METHODS: A combined PET/CT tomograph with the unique capability of acquiring accurately aligned functional and anatomical images for any part of the human body has been designed and built. The PET/CT scanner was developed as a combination of a Siemens Somatom AR.SP spiral CT and a partial-ring, rotating ECAT ART PET scanner. All components are mounted on a common rotational support within a single gantry. The PET and CT components can be operated either separately, or in combined mode. In combined mode, the CT images are used to correct the PET data for scatter and attenuation. Fully quantitative whole-body images are obtained for an axial extent of 100 cm in an imaging time of less than 1 h. When operated in PET mode alone, transmission scans are acquired with dual 137Cs sources. RESULTS: The scanner is fully operational and the combined device has been operated successfully in a clinical environment. Over 110 patients have been imaged, covering a range of different cancers, including lung, esophageal, head and neck, melanoma, lymphoma, pancreas, and renal cell. The aligned PET and CT images are used both for diagnosing and staging disease and for evaluating response to therapy. We report the first performance measurements from the scanner and present some illustrative clinical studies acquired in cancer patients. CONCLUSION: A combined PET and CT scanner is a practical and effective approach to acquiring co-registered anatomical and functional images in a single scanning session.
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PURPOSE: To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. METHODS: SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. RESULTS: GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensity. The panel recommended that the following domains be evaluated in a GA: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and presence of geriatric syndromes. Although several combinations of tools and various models are available for implementation of GA in oncology practice, the expert panel could not endorse one over another. CONCLUSION: There is mounting data regarding the utility of GA in oncology practice; however, additional research is needed to continue to strengthen the evidence base.
Part I: Molecular Biology of Cancer Molecular Methods in Oncology Section 1. Amplification Techniques Section 2. RNA Interference Section 3. cDNA arrays Section 4. Tissue arrays Section 5. Cytogenetics Section 6. Bioinformatics Genomics and Proteomics Molecular Targets in Oncology Section 1. Signal transduction systems Section 2. Cell cycle Section 3. Apoptosis Section 4. Telomerase Invasion and Metastases Angiogenesis Cancer Immunology Part II: Principles of Oncology Etiology of Cancer: Viruses Section 1. RNA Viruses Section 2. DNA Viruses Etiology of Cancer: Chemical Factors Etiology of Cancer: Tobacco Etiology of Cancer: Physical Factors Epidemiology of Cancer Section 1. Epidemiologic Methods Section 2. Cancer Statistics Principles of Surgical Oncology Section 1. General Issues Section 2. Laparascopic Surgery Principles of Radiation Oncology Principles of Medical Oncology Pharmacology of Cancer Chemotherapy Section 2. Pharmocokinetics Section 3. Pharmacogenomics Section 4. Alkylating Agents Section 5. Cisplatin and its Analogues Section 6. Antimetabolites Section 7. Topoisomerase Interactive Agents Section 8. Antimicrotubule Agents Section 9. Miscellaneous Chemotherapeutic Agents Pharmacology of Cancer Biotherapeutics Section 1. Interferon Section 2. Interleukin 2 Section 3. Histone deacetylase inhibitors as differentiation agents Section 4. Monoclonal Antibodies Pharmacology of Endocrine Manipulation Design and Analysis of Clinical Trials Part III: Practice of Oncology Cancer Prevention: Preventing Tobacco-Related Cancers Cancer Prevention: Diet and Chemopreventive Agents Section 1. Dietary fat Section 2. Dietary Fiber Section 3. Dietary fruits and vegetables: naturally occurring anticarcinogens Section 4. Retinoids, carotenoids and micronutrients Section 5. Dietary Carcinogens Section 6. Cyclo-oxygenase inhibitors Section 7. Physical Activity and Body Weight Cancer Prevention: Role of Surgery in Cancer Prevention Cancer Screening Advanced Molecular Diagnostics Advanced Imaging Methods Section 1. Functional and Metabolic Imaging Section 2. Interventional Radiology Cancer Diagnosis: Endoscopy Section 1. Gastrointestinal endoscopy Section 2. Respiratory Tract Cancer of the Head and Neck Section 1. Molecular Biology of Head and Neck Tumors Section 2. Treatment of Head and Neck Cancers Section 3. Rehabilitation after Treatment for Head Cancer of the Lung Section 1. Molecular Biology of Lung Cancer Section 2. Non-small Cell Lung Cancer Section 3. Small Cell Lung Cancer Neoplasms of the Mediastinum Cancers of the Gastrointestinal Tract
PURPOSE: An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This PCO addresses the integration of palliative care services into standard oncology practice at the time a person is diagnosed with metastatic or advanced cancer. CLINICAL CONTEXT: Palliative care is frequently misconstrued as synonymous with end-of-life care. Palliative care is focused on the relief of suffering, in all of its dimensions, throughout the course of a patient's illness. Although the use of hospice and other palliative care services at the end of life has increased, many patients are enrolled in hospice less than 3 weeks before their death, which limits the benefit they may gain from these services. By potentially improving quality of life (QOL), cost of care, and even survival in patients with metastatic cancer, palliative care has increasing relevance for the care of patients with cancer. Until recently, data from randomized controlled trials (RCTs) demonstrating the benefits of palliative care in patients with metastatic cancer who are also receiving standard oncology care have not been available. RECENT DATA: Seven published RCTs form the basis of this PCO. PROVISIONAL CLINICAL OPINION: Based on strong evidence from a phase III RCT, patients with metastatic non-small-cell lung cancer should be offered concurrent palliative care and standard oncologic care at initial diagnosis. While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology settings, substantial evidence demonstrates that palliative care-when combined with standard cancer care or as the main focus of care-leads to better patient and caregiver outcomes. These include improvement in symptoms, QOL, and patient satisfaction, with reduced caregiver burden. Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice, and reduced use of futile intensive care. While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving, no trials to date have demonstrated harm to patients and caregivers, or excessive costs, from early involvement of palliative care. Therefore, it is the Panel's expert consensus that combined standard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden. Strategies to optimize concurrent palliative care and standard oncology care, with evaluation of its impact on important patient and caregiver outcomes (eg, QOL, survival, health care services utilization, and costs) and on society, should be an area of intense research. NOTE: ASCO's provisional clinical opinions (PCOs) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and settings for further research. Because of the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical trials and cannot be assumed to apply to the use of these interventions in the context of clinical practice. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions.
pioneered studies that elucidated the potent effects of stress on the organism at the behavioral, neuroendocrine, cellular and molecular levels, and performed groundbreaking research on human development, particularly in early life and the years of puberty and adolescence.Dr Chrousos has performed a body of influential original experimental, translational and clinical studies on the universally pathogenic impact of a chronically activated stress system on human health.He identified and functionally characterized the molecular mechanisms underlying the pervasive stress hormone-mediated effects of chronically disrupted homeostasis on human mental and somatic health.His discoveries of the pathogenic mechanisms through which chronic stress causes and/or aggravates the ʻchronic noncommunicable diseasesʼ, promotes inflammation, increases vulnerability to certain cancers and infections, and accelerates aging, have had a major impact on the science and practice of medicine.Dr Chrousos demonstrated that chronically disturbed homeostasis and chronodisruption -anytime during the entire human lifespan -lead to the over-production and/or increased action of stress and inflammatory mediators, and cause and/or exacerbate the progressively deteriorating with age ʻchronic stress and inflammation syndromeʼ.This nosological entity not only includes the classic chronic non-communicable diseases, but also a broad host of other disorders, affecting a large percentage of living individuals, amounting to hundreds of millions of human beings.This syndrome consists of
Full integration of oncology and palliative care relies on the specific knowledge and skills of two modes of care: the tumour-directed approach, the main focus of which is on treating the disease; and the host-directed approach, which focuses on the patient with the disease. This Commission addresses how to combine these two paradigms to achieve the best outcome of patient care. Randomised clinical trials on integration of oncology and palliative care point to health gains: improved survival and symptom control, less anxiety and depression, reduced use of futile chemotherapy at the end of life, improved family satisfaction and quality of life, and improved use of health-care resources. Early delivery of patient-directed care by specialist palliative care teams alongside tumour-directed treatment promotes patient-centred care. Systematic assessment and use of patient-reported outcomes and active patient involvement in the decisions about cancer care result in better symptom control, improved physical and mental health, and better use of health-care resources. The absence of international agreements on the content and standards of the organisation, education, and research of palliative care in oncology are major barriers to successful integration. Other barriers include the common misconception that palliative care is end-of-life care only, stigmatisation of death and dying, and insufficient infrastructure and funding. The absence of established priorities might also hinder integration more widely. This Commission proposes the use of standardised care pathways and multidisciplinary teams to promote integration of oncology and palliative care, and calls for changes at the system level to coordinate the activities of professionals, and for the development and implementation of new and improved education programmes, with the overall goal of improving patient care. Integration raises new research questions, all of which contribute to improved clinical care. When and how should palliative care be delivered? What is the optimal model for integrated care? What is the biological and clinical effect of living with advanced cancer for years after diagnosis? Successful integration must challenge the dualistic perspective of either the tumour or the host, and instead focus on a merged approach that places the patient's perspective at the centre. To succeed, integration must be anchored by management and policy makers at all levels of health care, followed by adequate resource allocation, a willingness to prioritise goals and needs, and sustained enthusiasm to help generate support for better integration. This integrated model must be reflected in international and national cancer plans, and be followed by developments of new care models, education and research programmes, all of which should be adapted to the specific cultural contexts within which they are situated. Patient-centred care should be an integrated part of oncology care independent of patient prognosis and treatment intention. To achieve this goal it must be based on changes in professional cultures and priorities in health care.
PURPOSE: To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. METHODS: ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. RESULTS: The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. RECOMMENDATIONS: The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to > 10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. This guideline was developed through a collaboration between the American Society of Clinical Oncology and the College of American Pathologists and has been published jointly by invitation and consent in both Journal of Clinical Oncology and the Archives of Pathology & Laboratory Medicine.
International audience
PURPOSE: With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, there is an urgent need for a clinical support tool that distills the clinical implications associated with specific mutation events into a standardized and easily interpretable format. To this end, we developed OncoKB, an expert-guided precision oncology knowledge base. METHODS: OncoKB annotates the biological and oncogenic effect and the prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response based on US Food and Drug Administration (FDA) labeling, National Comprehensive Cancer Network (NCCN) guidelines, disease-focused expert group recommendations and the scientific literature. RESULTS: To date, over 3000 unique mutations, fusions, and copy number alterations in 418 cancer-associated genes have been annotated. To test the utility of OncoKB, we annotated all genomic events in 5983 primary tumor samples in 19 cancer types. Forty-one percent of samples harbored at least one potentially actionable alteration, of which 7.5% were predictive of clinical benefit from a standard treatment. OncoKB annotations are available through a public web resource (http://oncokb.org/) and are also incorporated into the cBioPortal for Cancer Genomics to facilitate the interpretation of genomic alterations by physicians and researchers. CONCLUSION: OncoKB, a comprehensive and curated precision oncology knowledge base, offers oncologists detailed, evidence-based information about individual somatic mutations and structural alterations present in patient tumors with the goal of supporting optimal treatment decisions.
STANDARD CRITERIA FOR TOXICITY and for response to treatment are important prerequisites to the conduct of cancer trials. The Eastern Cooperative Oncology Group criteria for toxicity and response are presented to facilitate future reference and to encourage further standardization among those conducting clinical trials.
Principles and practice of pediatric oncology , Principles and practice of pediatric oncology , کتابخانه دیجیتال جندی شاپور اهواز
Principles and practice of radiation oncology , Principles and practice of radiation oncology , کتابخانه دیجیتال جندی شاپور اهواز
Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.
Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.
Positron emission tomography (PET) provides metabolic information that has been documented to be useful in patient care. The properties of positron decay permit accurate imaging of the distribution of positron-emitting radiopharmaceuticals. The wide array of positron-emitting radiopharmaceuticals has been used to characterize multiple physiologic and pathologic states. PET is used for characterizing brain disorders such as Alzheimer disease and epilepsy and cardiac disorders such as coronary artery disease and myocardial viability. The neurologic and cardiac applications of PET are not covered in this review. The major utilization of PET clinically is in oncology and consists of imaging the distribution of fluorine 18 fluorodeoxyglucose (FDG). FDG, an analogue of glucose, accumulates in most tumors in a greater amount than it does in normal tissue. FDG PET is being used in diagnosis and follow-up of several malignancies, and the list of articles supporting its use continues to grow. In this review, the physics and instrumentation aspects of PET are described. Many of the clinical applications in oncology are mature and readily covered by third-party payers. Other applications are being used clinically but have not been as carefully evaluated in the literature, and these applications may not be covered by third-party payers. The developing applications of PET are included in this review.
PURPOSE: To update the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology. UPDATE METHODOLOGY: The Update Committee completed a review and analysis of data published from 1998 thru February 2006. The literature review focused on published randomized controlled trials, and systematic reviews and meta-analyses of published phase II and phase III randomized controlled trials. RECOMMENDATIONS: The three-drug combination of a 5-hydroxytryptamine-3 (5-HT(3)) serotonin receptor antagonist, dexamethasone, and aprepitant is recommended before chemotherapy of high emetic risk. For persons receiving chemotherapy of high emetic risk, there is no group of patients for whom agents of lower therapeutic index are appropriate first-choice antiemetics. These agents should be reserved for patients intolerant of or refractory to 5-HT3 serotonin receptor antagonists, neurokinin-1 receptor antagonists, and dexamethasone. The three-drug combination of a 5-HT3 receptor serotonin antagonist, dexamethasone, and aprepitant is recommended for patients receiving an anthracycline and cyclophosphamide. For patients receiving other chemotherapy of moderate emetic risk, the Update Committee continues to recommend the two-drug combination of a 5-HT3 receptor serotonin antagonist and dexamethasone. In all patients receiving cisplatin and all other agents of high emetic risk, the two-drug combination of dexamethasone and aprepitant is recommended for the prevention of delayed emesis. The Update Committee no longer recommends the combination of a 5-HT3 serotonin receptor antagonist and dexamethasone for the prevention of delayed emesis after chemotherapeutic agents of high emetic risk. CONCLUSION The Update Committee recommends that clinicians administer antiemetics while considering patients' emetic risk categories and other characteristics.
Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.
T he International Classification of Diseases for Oncology has been used for nearly 25 years as a tool for coding diagnoses of neoplasms in tumor and cancer registrars and in pathology laboratories.ICD-O is a dual classification with coding systems for both topography and morphology.T he topography code describes the site of origin of the neoplasm.T he morphology code describes the characteristics of the tumor itself, including its cell type and biologic activity.(from Amazon.com)