Seminars in Oncology RSS feed: Current Issue. Seminars in Oncology brings you current, authoritative, and practical reviews of developments in the diagnosis and management of patients with cancer. Each issue examines a single topic of clinical importance. You're guided through each cancer's biology, epidemiology, and pathophysiology, its clinical presentation and therapeutic options, and appropriate follow-up measures. This journal makes an excellent addition to every oncology practice. 2010 Topics , Volume 37 Nomograms as Prediction Tools Paul A. Fearn Advances in Radiation Oncology Walter J. Curran, Jr. Regional Hepatic Treatment of Cancer Brian I. Carr Cancer Prevention Peter Greenwald and Barbara Dunn Molecular and Translational Imaging Carolyn Meltzer and Hyunsuk Shim Immunologic Checkpoints Michele Maio http://www.seminoncol.org/?rss=yesElsevier Inc.en © 2010 Elsevier Inc. All rights reserved. Seminars in Oncology0093-7754373June 2010 © 2010 Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.seminoncol.org/article/PIIS0093775410000783/abstract?rss=yes At times we encounter clinical problems for which there are no directly applicable evidence-based solutions, but we are compelled by circumstances to act. When doing so we rely on related evidence, general principles of best medical practice, and our experience. Each ”Current Clinical Practice” feature article in Seminars in Oncology describes such a challenging presentation and offers treatment approaches from selected specialists. We invite readers' comments and questions, which, with your approval, will be published in subsequent issues of the Journal. It is hoped that sharing our views and experiences will better inform our management decisions when we next encounter similar challenging patients. Please send your comments on the articles, your challenging cases, and your treatment successes to me at Gloria.Morris@hemonc1.com. I look forward to a lively discussion.Gastric Mucosa-Associated Lymphoid Tissue LymphomaGloria J. Morris, Efrat Dotan, Mitchell R. Smith, Frederick B. Hagemeister, Harmar D. Brereton10.1053/j.seminoncol.2010.05.013Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Current Clinical Practice183187http://www.seminoncol.org/article/PIIS0093775410000898/abstract?rss=yes At times we encounter clinical problems for which there are no directly applicable evidence-based solutions, but we are compelled by circumstances to act. When doing so we rely on related evidence, general principles of best medical practice, and our experience. Each ”Current Clinical Practice” feature article in Seminars in Oncology describes such a challenging presentation and offers treatment approaches from selected specialists. We invite readers' comments and questions, which, with your approval, will be published in subsequent issues of the Journal. It is hoped that sharing our views and experiences will better inform our management decisions when we next encounter similar challenging patients. Please send your comments on the articles, your challenging cases, and your treatment successes to me at Gloria.Morris@hemonc1.com. I look forward to a lively discussion.The Role of Anti-Tumor Necrosis Factor Receptor Agents in Cancer Survivors RevisitedEdward F. McClay10.1053/j.seminoncol.2010.06.010Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Current Clinical Practice188189http://www.seminoncol.org/article/PIIS0093775410000904/abstract?rss=yesTwenty years ago Seminars in Oncology published a volume dedicated to Cancer Prevention and Control. Issues discussed in the earlier volume evolved out of prevention developments that gained prominence in the 1980s (). A wealth of epidemiologic data supporting associations of exogenous factors such as tobacco and diet/body mass index (BMI)/physical activity with increased or decreased cancer risk had emerged during this period. These observations offered hypotheses for clinical trials centering around behavioral modifications directed at avoiding newly understood carcinogenic exposures and increasing exposure to risk-reducing factors. In addition, initiatives were undertaken that addressed improvements in communication of prevention strategies and health promotion to the public, developing methodological approaches to clinical cancer prevention trial design, and undertaking rigorously designed trials to test modalities for cancer screening and early detection.Cancer Prevention I: IntroductionBarbara K. Dunn, Peter Greenwald10.1053/j.seminoncol.2010.06.011Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Barbara K. Dunn, MD, PhD, and Peter Greenwald, MD, DrPH, Guest Editors190201http://www.seminoncol.org/article/PIIS0093775410000710/abstract?rss=yesEarly detection of cancer has held great promise and intuitive appeal in the medical community for well over a century. Its history developed in tandem with that of the periodic health examination, in which any deviations—subtle or glaring—from a clearly demarcated “normal” were to be rooted out, given the underlying hypothesis that diseases develop along progressive linear paths of increasing abnormalities. This model of disease development drove the logical deduction that early detection, by “breaking the chain” of cancer development, must be of benefit to affected individuals. In the latter half of the 20th century, researchers and guidelines organizations began to explicitly challenge the core assumptions underpinning many clinical practices. A move away from intuitive thinking began with the development of evidence-based medicine. One key method developed to explicitly quantify the overall risk–benefit profile of a given procedure was the analytic framework. The shift away from pure deductive reasoning and reliance on personal observation was driven, in part, by a rising awareness of critical biases in cancer screening that can mislead clinicians, including healthy volunteer bias, length-biased sampling, lead-time bias, and overdiagnosis. A new focus on the net balance of both benefits and harms when determining the overall worth of an intervention also arose: it was recognized that the potential downsides of early detection were frequently overlooked or discounted because screening is performed on basically healthy persons and initially involves relatively noninvasive methods. Although still inconsistently applied to early detection programs, policies, and belief systems in the United States, an evidence-based approach is essential to counteract the misleading—even potentially harmful—allure of intuition and individual observation.Principles of Cancer Screening: Lessons From History and Study Design IssuesJennifer M. Croswell, David F. Ransohoff, Barnett S. Kramer10.1053/j.seminoncol.2010.05.006Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Barbara K. Dunn, MD, PhD, and Peter Greenwald, MD, DrPH, Guest Editors202215http://www.seminoncol.org/article/PIIS0093775410000746/abstract?rss=yesThe most rigorous and valid approach to evaluating cancer screening modalities is the randomized controlled trial (RCT). RCTs are major undertakings and the intricacies of trial design, operations, and management are generally underappreciated by the typical researcher. The purpose of this article is to inform the reader of the “nuts and bolts” of designing and conducting cancer screening RCTs. Following a brief introduction as to why RCTs are critical in evaluating screening modalities, we discuss design considerations, including the choice of design type and duration of follow-up. We next present an approach to sample-size calculations. We then discuss aspects of trial implementation, including recruitment, randomization, and data management. A discussion of commonly employed data analyses comes next, and includes methods for the primary analysis (comparison of cause-specific mortality rates between the screened and control arms for the cancer of interest), as well as for secondary endpoints such as sensitivity. We follow with a discussion of sequential monitoring and interim analysis techniques, which are used to examine the primary outcome while the trial is ongoing. We close with thoughts on lessons learned from past cancer screening RCTs and provide recommendations for future trials. Throughout the presentation we illustrate topics with examples from completed or ongoing RCTs, including the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the National Lung Screening Trial (NLST).Cancer Screening Trials: Nuts and BoltsPhilip C. Prorok, Pamela M. Marcus10.1053/j.seminoncol.2010.05.009Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Barbara K. Dunn, MD, PhD, and Peter Greenwald, MD, DrPH, Guest Editors216223http://www.seminoncol.org/article/PIIS0093775410000722/abstract?rss=yesA common belief is that the earlier that cancer is detected, the better the chance exists for reduced mortality and morbidity. The advent of new and emerging molecular, genetic, and imaging technologies has broadened the possible strategies for early detection and prevention, but a beneficial impact on mortality needs to be supported by clinical evidence. Molecular markers are being identified that are enhancing our ability to predict and detect cancer before it develops and at the earliest signs of impending carcinogenic transformation. Of the innumerable molecular markers in development, a standalone early detection marker with acceptable sensitivity and specificity is available for bladder cancer, although for most cancer sites there are promising avenues of research that will likely produce results in the next decade. The perfect molecular marker would be one that is inherently related to the disease, specifically to the processes of malignant tumorigenesis or to the defense mechanisms of the individual. For example, mutations associated with increased cancer risk often produce gene products that interfere with tumor-suppressor pathways (eg, DNA repair or cell-cycle control) or support oncogenic pathways (eg, through genetic instability or silencing the apoptotic pathway). Finding molecular markers associated with these processes, and where in the process they produce their actions, can lead to interventions based on maintaining support for the normal process and interrupting the action of the products of the mutation. The search for molecular markers for cancer prevention and early detection presents a formidable challenge that requires a systematic and scientifically sound validation process. The search encompasses a broad range of scientific disciplines, including biochemistry, genetics, histology, immunology, informatic technologies, and epidemiology; strategies to identify and understand molecular markers are approached with multidisciplinary teams focused on understanding the mechanistic basis of cancer and the processes and pathways that underlie carcinogenesis.Molecular Markers for Early DetectionBarbara K. Dunn, Paul D. Wagner, Darrell Anderson, Peter Greenwald10.1053/j.seminoncol.2010.05.007Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Barbara K. Dunn, MD, PhD, and Peter Greenwald, MD, DrPH, Guest Editors224242http://www.seminoncol.org/article/PIIS0093775410000667/abstract?rss=yesMalignant cells are characterized by abnormal signaling pathways involving proliferation, apoptosis, and angiogenesis. These cancer centric pathways are known to be modified by several bioactive dietary components, although admittedly there are inconsistencies in the response. The response is dependent on the amount and duration of exposure to the dietary component and the cell type. While caution should be exercised when extrapolating in vitro data to in vivo conditions, such studies do provide valuable insights into plausible mechanisms. Significant gene–nutrient and nutrient–nutrient interactions may contribute to the uncertainty of the response to foods and/or their components. One of the challenges is the identification of which process(es), either singly or in combination, is/are most important in leading to a dietary-mediated phenotypic change. The dearth of controlled intervention studies that have investigated molecular targets for nutritional preemption in humans make firm dietary recommendations difficult. Until more definite information surfaces, a balanced but varied diet is most prudent.Cellular Proliferation, Apoptosis and Angiogenesis: Molecular Targets for Nutritional Preemption of CancerCindy D. Davis, Nancy J. Emenaker, John A. Milner10.1053/j.seminoncol.2010.05.001Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Barbara K. Dunn, MD, PhD, and Peter Greenwald, MD, DrPH, Guest Editors243257http://www.seminoncol.org/article/PIIS009377541000093X/abstract?rss=yesBotanical and nutritional compounds have been used for the treatment of cancer throughout history. These compounds also may be useful in the prevention of cancer. Population studies suggest that a reduced risk of cancer is associated with high consumption of vegetables and fruits. Thus, the cancer chemopreventive potential of naturally occurring phytochemicals is of great interest. There are numerous reports of cancer chemopreventive activity of dietary botanicals, including cruciferous vegetables such as cabbage and broccoli, Allium vegetables such as garlic and onion, green tea, Citrus fruits, soybeans, tomatoes, berries, and ginger, as well as medicinal plants. Several lead compounds, such as genistein (from soybeans), lycopene (from tomatoes), brassinin (from cruciferous vegetables), sulforaphane (from asparagus), indole-3-carbinol (from broccoli), and resveratrol (from grapes and peanuts) are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals have great potential in cancer prevention because of their safety, low cost, and oral bioavailability. In this review, we discuss potential natural cancer preventive compounds and their mechanisms of action.Cancer Prevention With Natural CompoundsNorleena P. Gullett, A.R.M. Ruhul Amin, Soley Bayraktar, John M. Pezzuto, Dong M. Shin, Fadlo R. Khuri, Bharat B. Aggarwal, Young-Joon Surh, Omer Kucuk10.1053/j.seminoncol.2010.06.014Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Barbara K. Dunn, MD, PhD, and Peter Greenwald, MD, DrPH, Guest Editors258281http://www.seminoncol.org/article/PIIS009377541000076X/abstract?rss=yesIn this review, we briefly summarize some of the key developments in nutritional epidemiology and cancer over the past two decades with a focus on the strengths and limitations of study designs and dietary assessment methods. We present the evidence on dietary fat, meat, fiber, antioxidant nutrients, and calcium in relation to carcinogenesis from large cohort studies and randomized clinical trials (RCTs) and refer to the conclusions of the 2007 World Cancer Research Fund/American Institute for Cancer Research summary report. One prominent theme that emerged is the lack of concordance of results from RCTs and observational studies. There are multiple potential reasons for these discrepancies, including differences in study population, dose and timing of the exposure, adherence to an intervention, length of follow-up, and the primary endpoint. Therefore, null findings of RCTs do not necessarily indicate a lack of effect for the tested dietary factors on cancer risk, as some of these nutrients may have chemopreventive effects if given at the right time and in the right dose. It is likely that potential benefits from diet are due to a combination of food constituents rather than single components acting in isolation. Future efforts need to recognize the integrative nature of dietary exposures and attempt to study nutrients in the larger context of the foods and diets in which they are consumed.Epidemiological and Clinical Studies of NutritionTodd M. Gibson, Leah M. Ferrucci, Joseph A. Tangrea, Arthur Schatzkin10.1053/j.seminoncol.2010.05.011Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Barbara K. Dunn, MD, PhD, and Peter Greenwald, MD, DrPH, Guest Editors282296http://www.seminoncol.org/article/PIIS0093775410000734/abstract?rss=yesConsiderable research interest has been given in the past 25 years to examining the role of physical activity in breast cancer prevention given the scarcity of modifiable risk factors for this major cause of cancer incidence and mortality in women. A review of the observational epidemiologic evidence and recent randomized exercise intervention trials on the association between physical activity and breast cancer risk is presented. As of March 2010, 73 separate studies out of 91 publications worldwide were identified as having sufficient data for this review. Across these 73 studies, the average reduction in breast cancer risk, when comparing the most to the least physically active women, was 25%. There also was evidence for a dose-response effect found in the majority of studies that examined this trend. The strongest associations were found for recreational and household activities and for activity that was of at least moderate intensity and sustained over a lifetime. Within population subgroups, a stronger effect was seen in women who are normal weight, in women without a family history of breast cancer, and in women who are parous. Women of all races benefitted from physical activity; however, a particularly strong effect on breast cancer risk was observed in non-Caucasian women. Future research should focus on elucidating the exact type, dose, and timing of physical activity required to reduce breast cancer risk. Prospective observational epidemiologic studies of lifetime physical activity patterns and breast cancer risk would help in this regard, as well as randomized controlled exercise intervention trials employing hypothesized biomarkers of breast cancer risk as outcome measures. Additional consideration to the role of sedentary behavior and light-intensity activity also is needed, as well as improved physical activity assessment methods. These additional data will be useful in improving public health recommendations regarding physical activity for breast cancer risk reduction.The Role of Physical Activity in Breast Cancer EtiologyChristine M. Friedenreich10.1053/j.seminoncol.2010.05.008Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7Barbara K. Dunn, MD, PhD, and Peter Greenwald, MD, DrPH, Guest Editors297302http://www.seminoncol.org/article/PIIS0093775410001065/abstract?rss=yesMasthead10.1053/S0093-7754(10)00106-5Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7FrontmatterA4A4http://www.seminoncol.org/article/PIIS0093775410001089/abstract?rss=yesContents10.1053/S0093-7754(10)00108-9Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7FrontmatterA5A6http://www.seminoncol.org/article/PIIS0093775410001077/abstract?rss=yesEditorial Board10.1053/S0093-7754(10)00107-7Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7FrontmatterA13A13http://www.seminoncol.org/article/PIIS0093775410001090/abstract?rss=yesFuture and Previous Issues10.1053/S0093-7754(10)00109-0Seminars in Oncology 37, 3 (2010)2010-06-01Seminars in Oncology2010-06-01373S0093-7754(10)X0005-7FrontmatterA16A16