High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.
The rationale was to develop recommendations on the use of 18 F-FDG PET in breast, colorectal, esophageal, head and neck, lung, pancreatic, and thyroid cancer; lymphoma, melanoma, and sarcoma; and unknown primary tumor. Outcomes of interest included the use of 18 F-FDG PET for diagnosing, staging, and detecting the recurrence or progression of cancer. Methods: A search was performed to identify all published randomized controlled trials and systematic reviews in the literature. An additional search was performed to identify relevant unpublished systematic reviews. These publications comprised both retrospective and prospective studies of varied methodologic quality. The anticipated consequences of false-positive and false-negative tests when evaluating clinical usefulness, and the impact of 18 F-FDG PET on the management of cancer patients, were also reviewed. Results and Conclusion: 18 F-FDG PET should be used as an imaging tool additional to conventional radiologic methods such as CT or MRI; any positive finding that could lead to a clinically significant change in patient management should be confirmed by subsequent histopathologic examination because of the risk of false-positive results. 18 F-FDG PET should be used in the appropriate clinical setting for the diagnosis of head and neck, lung, or pancreatic cancer and for unknown primary tumor. PET is also indicated for staging of breast, colon, esophageal, head and neck, and lung cancer and of lymphoma and melanoma. In addition, 18 F-FDG PET should be used to detect recurrence of breast, colorectal, head and neck, or thyroid cancer and of lymphoma. PET is an imaging technique that provides unique information about the molecular and metabolic changes associated with disease. The technology has existed for more than 30 years but has been used clinically for only the last 10-15 years. In this period, dramatic improvements in technology, the routine availability of medical cyclotrons (to produce the necessary short-lived positron emitters), and favorable reimbursement decisions in the late 1990s have led to a tremendous increase in the use of this technology. The major area of clinical application is currently in oncology, with some application in cardiology and neurology.PET requires the use of molecules (radiopharmaceuticals) that are labeled with radioactive nuclides. The amounts of radiolabeled material administered are extremely small (10 26 -10 29 g) and have essentially no pharmacologic effect. In this regard, PET has the unique ability to assess molecular alterations associated with disease without perturbing or altering the fundamental underlying molecular and biochemical processes. Although the number of molecular probes that can be radiolabeled with positron emitters is extremely large, and clinical investigational uses number in the thousands, clinical practice has been limited principally to the use of a glucose analog labeled with the positron emitter 18 F-FDG. 18 F-FDG was first synthesized in 1978 (1) and has become the most commonly used radioph...
The use of standardized uptake values (SUVs) is now common place in clinical FDG-PET/CT oncology imaging, and has a specific role in assessing patient response to cancer therapy. Ideally, the use of SUVs removes variability introduced by differences in patient size and the amount of injected FDG. However, in practice there are several sources of bias and variance that are introduced in the measurement of FDG uptake in tumors and also in the conversion of the image count data to SUVs. The overall imaging process is reviewed and estimates of the magnitude of errors, where known, are given. Recommendations are provided for best practices in improving SUV accuracy. The use of Standardized Uptake Values in FDG-PET ImagingPET/CT imaging of cancer with combined positron emission tomography (PET) and x-ray computerized tomography (CT) scanners has become a standard component of diagnosis and staging in oncology 1,2 . The use of the radiolabeled tracer 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) for oncology imaging accounts for the majority of all PET/CT imaging procedures since increased accumulation of FDG relative to normal tissue is a useful marker for many cancers 3 .In addition to cancer detection and staging, PET/CT imaging is becoming more important as a quantitative monitor of individual response to therapy and an evaluation tool for new drug therapies. Changes in FDG accumulation have been shown to be useful as an imaging biomarker for assessing response to therapy 4 . However, FDG uptake in tumors is related in a complex manner to the proliferative activity of malignant tissue and to the number of viable tumor cells 5 .There are several methods for measuring the rate and/or total amount of FDG accumulation in tumors. PET scanners are designed to measure the in vivo radioactivity concentration [kBq/ml], which is directly linked to the FDG concentration. Typically, however, it is the relative tissue uptake of FDG that is of interest. The two most significant sources of variation that occur in practice are the amount of injected FDG and the patient size. To * Corresponding author. Department of Radiology, University of Washington, 222 Fisheries Center (FIS), Box 357987, Seattle, kinahan@uw.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptSemin Ultrasound CT MR. Author manuscript; available in PMC 2011 December 1. compensate for these variations, at least to first order, the standardized uptake value (SUV) is commonly used as a relative measure of FDG uptake 6 . The basic expression for SUV is [1] where r is the radioactivity acti...
We present equations for calculating dry weight from body length for 14 common and widely distributed taxa of crustacean zooplankters; these were generated by regression from weights of individuals chosen from the range of lengths observed for each taxon, usually three replicate weights at each of five lengths. We include regressions for ovigerous and nonovigerous cladocerans, plus nauplii, early copepodites, and adult males and females for the copepods (30 length–weight relationships) and individual weights for given stages of copepods. We calculated the seasonal variation in crustacean biomass for a station in the Bay of Quinte, Lake Ontario, and for each of the three basins of Lake Erie. Biomass was dominated by Cladocera for both lakes, with Copepoda predominant in the spring. Mean individual dry weights varied seasonally for all taxa, confirming previous findings.
FDG-PET can accurately characterize indeterminate SPNs. PET imaging provides a noninvasive method to evaluate indeterminate SPNs, which can reduce the need for invasive tissue biopsy.
Summary BACKGROUND Plexiform neurofibromas (PN) are slow growing chemoradiotherapy resistant tumours arising in patients with neurofibromatosis type I (NF1). Currently there are no viable therapeutic options for patients whose life-threatening plexiform neurofibromas cannot be surgically removed due to proximity to vital body structures. Based on identification of molecular targets in genetic mouse models of human NF1 tumours, we hypothesized that the oral kinase inhibitor, imatinib mesylate, may be effective in targeted treatment of these chemoradiotherapy-refractory tumours. METHODS An open-label pilot Phase II clinical trial was designed to test whether treatment with imatinib mesylate can decrease volume burden of clinically significant plexiform neurofibromas in NF1 patients. The entry criteria require patients only to have NF1 and a clinically significant plexiform neurofibroma with the specified age limitations (age 3–65). Patients were treated with daily oral imatinib at 440 mg/m2/day for children and 800 mg/day for adults divided twice daily for 6 months. The primary endpoint measure of significant response was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data was analyzed on an intent to treat basis, however to determine the activity of imatinib on NF1-related plexiform tumours, patients able to take imatinib for 6 months were evaluated for their response. Secondary outcomes included evaluation of safety of imatinib mesylate in this group of patients. The trial is registered at http://clinicaltrials.gov/; study number 0512-25. The trial currently is closed to enrollment, however there is a single patient that continues to respond and remains on study. FINDINGS On an intent to treat basis, 6 out of 36 patients or 17% (95% CI: 6 – 33%) experienced objective response to imatinib mesylate. In the evaluable study population of patients (n=23) who received drug for at least six months, six patients (26%; 95% CI: 10 – 48%) experienced ≥ 20% decrease in volume of one or more plexiform tumours and 30% of study patients had symptomatic improvement. We noted significant inter-patient and intra-patient heterogeneity of plexiform neurofibroma response. Toxicity of drug was comparable to previous reports in patients with chronic myelogenous leukemia. The most common adverse events were reversible skin rash (5 patients) and edema with weight gain (6 patients). More serious adverse events included reversible grade 3 neutropenia (2 patients) and grade 4 transaminitis (one patient). INTERPRETATION Imatinib mesylate caused disease regression in 26% of evaluable patients with clinically significant plexiform neurofibromas due to neurofibromatosis type 1. These results warrant confirmation in a larger multi-institutional clinical trial aimed at this patient population. These findings provide the first demonstration of radiographic volumetric tumour reduction in response to medical therapy in patients with NF1 plexiform neurofibromas using imatinib mesylate based on studies...
The potential for leukemia caused by retroviral vector integration has become a significant concern for hematopoietic stem cell gene therapy. We analyzed the distribution of vector integrants in pigtailed macaque and baboon repopulating cells for the two most commonly used retroviral vector systems, human immunodeficiency virus (HIV)-based lentiviral vectors and murine leukemia virus (MLV)-based gammaretroviral vectors, to help define their relative genotoxicity. All animals had polyclonal engraftment with no apparent adverse effects from transplantation with gene-modified cells. In all, 380 MLV and 235 HIV unique vector integration sites were analyzed and had distinct distribution patterns in relation to genes and CpG islands as observed in previous in vitro studies. Both vector types were found more frequently in and near proto-oncogenes in repopulating cells than in a random dataset. Analysis of functional classes of genes with integrants within 100 kilobases (kb) of their transcription start sites showed an over-representation of genes involved in growth or survival near both lentiviral and gammaretroviral integrants. Microarray analysis showed that both gammaretroviral and lentiviral vectors were found close to genes with high expression levels in primitive cells enriched for hematopoietic stem cells. These data help define the relative risk of insertional mutagenesis with MLV-, HIV-, and simian immunodeficiency virus (SIV)-based vectors in a highly relevant primate model.
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