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PubMed2001

Intensity-modulated radiotherapy: current status and issues of interest.

PURPOSE: To develop and disseminate a report aimed primarily at practicing radiation oncology physicians and medical physicists that describes the current state-of-the-art of intensity-modulated radiotherapy (IMRT). Those areas needing further research and development are identified by category and recommendations are given, which should also be of interest to IMRT equipment manufacturers and research funding agencies. METHODS AND MATERIALS: The National Cancer Institute formed a Collaborative Working Group of experts in IMRT to develop consensus guidelines and recommendations for implementation of IMRT and for further research through a critical analysis of the published data supplemented by clinical experience. A glossary of the words and phrases currently used in IMRT is given in the. Recommendations for new terminology are given where clarification is needed. RESULTS: IMRT, an advanced form of external beam irradiation, is a type of three-dimensional conformal radiotherapy (3D-CRT). It represents one of the most important technical advances in RT since the advent of the medical linear accelerator. 3D-CRT/IMRT is not just an add-on to the current radiation oncology process; it represents a radical change in practice, particularly for the radiation oncologist. For example, 3D-CRT/IMRT requires the use of 3D treatment planning capabilities, such as defining target volumes and organs at risk in three dimensions by drawing contours on cross-sectional images (i.e., CT, MRI) on a slice-by-slice basis as opposed to drawing beam portals on a simulator radiograph. In addition, IMRT requires that the physician clearly and quantitatively define the treatment objectives. Currently, most IMRT approaches will increase the time and effort required by physicians, medical physicists, dosimetrists, and radiation therapists, because IMRT planning and delivery systems are not yet robust enough to provide totally automated solutions for all disease sites. Considerable research is needed to model the clinical outcomes to allow truly automated solutions. Current IMRT delivery systems are essentially first-generation systems, and no single method stands out as the ultimate technique. The instrumentation and methods used for IMRT quality assurance procedures and testing are not yet well established. In addition, many fundamental questions regarding IMRT are still unanswered. For example, the radiobiologic consequences of altered time-dose fractionation are not completely understood. Also, because there may be a much greater ability to trade off dose heterogeneity in the target vs. avoidance of normal critical structures with IMRT compared with traditional RT techniques, conventional radiation oncology planning principles are challenged. All in all, this new process of planning and treatment delivery has significant potential for improving the therapeutic ratio and reducing toxicity. Also, although inefficient currently, it is expected that IMRT, when fully developed, will improve the overall efficiency with which external beam RT can be planned and delivered, and thus will potentially lower costs. CONCLUSION: Recommendations in the areas pertinent to IMRT, including dose-calculation algorithms, acceptance testing, commissioning and quality assurance, facility planning and radiation safety, and target volume and dose specification, are presented. Several of the areas in which future research and development are needed are also indicated. These broad recommendations are intended to be both technical and advisory in nature, but the ultimate responsibility for clinical decisions pertaining to the implementation and use of IMRT rests with the radiation oncologist and radiation oncology physicist. This is an evolving field, and modifications of these recommendations are expected as new technology and data become available.

Algorithms↗
PubMed2003

National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002.

BACKGROUND: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. State-of-the-Science Process: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov. CONCLUSIONS: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.

Biomedical Research↗
PubMed1997

Therapy of hepatitis C: overview.

Based on the first decade of research on alpha interferon in viral hepatitis, one can conclude that up to 40% of patients with compensated chronic hepatitis C and elevated alanine aminotransferase (ALT) levels will respond at least transiently to interferon. Four forms of alpha interferon have been evaluated in large numbers of patients with chronic hepatitis C: alfa-2b, alfa-2a, alfa-n1, and consensus interferon (CIFN). Responses are defined on the basis of biochemical (ALT) or virological (hepatitis C virus [HCV] RNA testing by polymerase chain reaction [PCR]) end points, and as end-of-treatment response (ETR) or sustained response (SR). Biochemical ETR rates to 6 months of therapy range from 35% to 50%, and SR rates 6 months after treatment from 8% to 21%. Although 6-month treatment courses are associated with a significant rate of relapse, 12 months of initial treatment and re-treatment regimens markedly improve the SR rate. Long-term follow-up evaluation in patients with an SR to interferon consistently show long-lasting and significant clinical, virological, and histological improvement. Finally, baseline factors that have been shown to be associated with SR to 6 months of treatment are not accurate enough to predict response. Therefore, the best treatment strategy is a therapeutic trial. Further studies of interferon therapy of hepatitis C are needed to define better virological end points useful in stopping therapy, to understand and better manage significant side effects of interferon, and to evaluate the histological effects of interferon in biochemical nonresponders. Also needed is a better understanding of the causes of resistance to interferon. Finally, newer therapeutic regimens such as the use of induction therapy and combination therapies with ribavirin, other antiviral agents, cytokines, and cytokine modifiers are of primary importance in eventually developing safe and effective means of treatment of hepatitis C.

Antiviral Agents↗
PubMed2003

The Bethesda System 2001: an update of new terminology for gynecologic cytology.

From the inception of TBS in 1988, it has been well received by the pathology and clinical communities. The need for a unifying system of nomenclature was so great that most of the laboratories in the United States, as well as in numerous countries worldwide, quickly adopted TBS. By 1991, only 2 years after the initial publication of the initial TBS, 57% of United States laboratories were using the system. By 1994, almost 90% of laboratories were using TBS [28]. Although explanations for such a quick acceptance of TBS are many, one of the leading reasons is, most certainly, the sound and thoughtful basis for all of the elements of TBS. These include: (1) nomenclature that provides uniform diagnostic terminology to facilitate unambiguous communication between the laboratory and the clinician; (2) diagnostic categories that incorporate the latest scientific information on the pathogenesis and prognosis of cervical lesions; and (3) incorporation of the evaluation of specimen adequacy as an integral part of the report. From the beginning, TBS was more than just a diagnostic lexicon. When Drs. Kurman and Solomon decided that something had to be done about the diagnostic mess in GYN cytology, they did not develop another system. Instead, they convened an international consensus conference to look at the problem and come up with a comprehensive, relevant solution. The input from the entire community, which lent strength to the initial TBS, has continued to the present. This is highlighted by the enormous amount of input that was received by the 2001 TBS forum groups that enabled them to fine tune the existing terminology to meet the needs of today's clinicians. The result, continues to be an evolving, comprehensive, and clinically relevant entity, that should meet the needs of pathologists and clinicians for the foreseeable future.

Cell Biology↗
PubMed2003

Hepatitis C and renal disease: an update.

Hepatitis C is both a cause and a complication of chronic renal disease. Chronic infection with hepatitis C virus (HCV) can lead to the immune complex syndromes of cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN). The pathogenetic mechanisms for these conditions have not been defined, although they are clearly caused by the chronic viral infection. Management of HCV-related cryoglobulinemia and MPGN is difficult; antiviral therapy is effective in clearing HCV infection in a proportion of patients, but these conditions can be severe and resistant to antiviral therapy. Hepatitis C also is a complicating factor among patients with end-stage renal disease and renal transplants. The source of HCV infection in these patients can be nosocomial. Screening and careful attention to infection control precautions are mandatory for dialysis units to prevent the spread of hepatitis C. Prevention of spread is particularly important in these patients because HCV infection is associated with significant worsening of survival on dialysis therapy, as well as after kidney transplantation. Furthermore, therapy for hepatitis C is problematic, only partially effective, and associated with significant side effects in this population. There are significant needs in both basic and clinical research in the pathogenesis, natural history, prevention, and therapy for hepatitis C in patients with renal disease.

Animals↗
PubMed1991

Geriatric evaluation and management units: experimental methods for evaluating efficacy.

A multi-site randomized controlled trial could most conclusively establish the efficacy of geriatric evaluation and management units, but many questions must be answered to design such a trial. First, the research questions needs to be rigorously specified. This will facilitate decisions concerning the types of patients to be included in the study. Second, the intervention requires a clear definition, including its component parts, to improve replication across multiple sites. Third, the type of randomization (ie, by hospital or by patient) and the timing of randomization (ie, at admission or at some later point during care) need to be considered. Fourth, because this type of intervention cannot be administered in a blind fashion, bias is a critical concern. Outcome measures must be selected carefully so that those least susceptible to bias are given the highest priority. Despite the need to address all of these questions, the time is upon us to conduct a multi-site trial of geriatric evaluation and management programs.

Bias↗