Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease.

Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need for biomarker confirmation of amyloid pathology. Blood biomarker (BBM) tests for amyloid pathology are more acceptable, accessible and scalable than amyloid PET or cerebrospinal fluid (CSF) tests, but have highly variable levels of performance. The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to consider the minimum acceptable performance of BBM tests for clinical use. Amyloid PET status was identified as the reference standard. For use as a triaging test before subsequent confirmatory tests such as amyloid PET or CSF tests, the BBM Workgroup recommends that a BBM test has a sensitivity of ≥90% with a specificity of ≥85% in primary care and ≥75-85% in secondary care depending on the availability of follow-up testing. For use as a confirmatory test without follow-up tests, a BBM test should have performance equivalent to that of CSF tests - a sensitivity and specificity of ~90%. Importantly, the predictive values of all biomarker tests vary according to the pre-test probability of amyloid pathology and must be interpreted in the complete clinical context. Use of BBM tests that meet these performance standards could enable more people to receive an accurate and timely Alzheimer disease diagnosis and potentially benefit from new treatments.

Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. Amyloid Imaging Task Force of the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging.

Amyloid PET imaging is a novel diagnostic test that can detect in living humans one of the two defining pathologic lesions of Alzheimer disease, amyloid-ß deposition in the brain. The Amyloid Imaging Task Force of the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging previously published appropriate use criteria for amyloid PET as an important tool for increasing the certainty of a diagnosis of Alzheimer disease in specific patient populations. Here, the task force further clarifies and expands 3 topics discussed in the original paper: first, defining dementia experts and their use of proper documentation to demonstrate the medical necessity of an amyloid PET scan; second, identifying a specific subset of individuals with mild cognitive impairment for whom an amyloid PET scan is appropriate; and finally, developing educational programs to increase awareness of the amyloid PET appropriate use criteria and providing instructions on how this test should be used in the clinical decision-making process.

From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors.

UNLABELLED: The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with (18)F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0. METHODS: PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors' experience, draft criteria were formulated for PET tumor response to treatment. RESULTS: Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has limitations in response assessments. For example, despite effective treatment, changes in tumor size can be minimal in tumors such as lymphomas, sarcoma, hepatomas, mesothelioma, and gastrointestinal stromal tumor. CT tumor density, contrast enhancement, or MRI characteristics appear more informative than size but are not yet routinely applied. RECIST criteria may show progression of tumor more slowly than WHO criteria. RECIST 1.1 criteria (assessing a maximum of 5 tumor foci, vs. 10 in RECIST) result in a higher complete response rate than the original RECIST criteria, at least in lymph nodes. Variability appears greater in assessing progression than in assessing response. Qualitative and quantitative approaches to (18)F-FDG PET response assessment have been applied and require a consistent PET methodology to allow quantitative assessments. Statistically significant changes in tumor standardized uptake value (SUV) occur in careful test-retest studies of high-SUV tumors, with a change of 20% in SUV of a region 1 cm or larger in diameter; however, medically relevant beneficial changes are often associated with a 30% or greater decline. The more extensive the therapy, the greater the decline in SUV with most effective treatments. Important components of the proposed PERCIST criteria include assessing normal reference tissue values in a 3-cm-diameter region of interest in the liver, using a consistent PET protocol, using a fixed small region of interest about 1 cm(3) in volume (1.2-cm diameter) in the most active region of metabolically active tumors to minimize statistical variability, assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional) most metabolically active tumor focus as a continuous variable, requiring a 30% decline in SUV for "response," and deferring to RECIST 1.1 in cases that do not have (18)F-FDG avidity or are technically unsuitable. Criteria to define progression of tumor-absent new lesions are uncertain but are proposed. CONCLUSION: Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria have limitations, particularly in assessing the activity of newer cancer therapies that stabilize disease, whereas (18)F-FDG PET appears particularly valuable in such cases. The proposed PERCIST 1.0 criteria should serve as a starting point for use in clinical trials and in structured quantitative clinical reporting. Undoubtedly, subsequent revisions and enhancements will be required as validation studies are undertaken in varying diseases and treatments.

Standards for PET image acquisition and quantitative data analysis.

Quantitative (18)F-FDG PET is increasingly being recognized as an important tool for diagnosis, determination of prognosis, and response monitoring in oncology. However, PET quantification with, for example, standardized uptake values (SUVs) is affected by many technical and physiologic factors. As a result, some of the variations in the literature on SUV-based patient outcomes are explained by differences in (18)F-FDG PET study methods. Various technical and clinical studies have been performed to understand the factors affecting PET quantification. On the basis of the results of those studies, several recommendations and guidelines have been proposed with the aims of improving the image quality and the quantitative accuracy of (18)F-FDG PET studies. In this contribution, an overview of recommendations and guidelines for quantitative (18)F-FDG PET studies in oncology is provided. Special attention is given to the rationale underlying certain recommendations and to some of the differences in various guidelines.

The Dichotomy of Alzheimer's Disease Pathology: Amyloid-ß and Tau.

In this issue, an article by Tiepolt et al. shows that PET scanning using [11C]PiB can demonstrate both cerebral blood flow (CBF) changes and amyloid-ß (Aß) deposition in patients with mild cognitive dysfunction or mild dementia of Alzheimer's disease (AD). The CBF changes can be determined because the early scan counts (1-9 minutes) reflect the flow of the radiotracer in the blood passing through the brain, while the Aß levels are measured by later scan counts (40-70 minutes) after the radiotracer has been cleared from regions to which the radiotracer did not bind. Thus, two different diagnostic measures are obtained with a single injection. Unexpectedly, the mild patients with Aß positivity had scan data with only a weak relationship to memory, while the relationships to executive function and language function were relatively strong. This divergence of findings from studies of severely impaired patients highlights the importance of determining how AD pathology affects the brain. A possibility suggested in this commentary is that Aß deposits occur early in AD and specifically in critical areas of the neocortex affected only later by the neurofibrillary pathology indicating a different role of the amyloid-ß protein precursor (AßPP) in the development of those neocortical regions, and a separate component of AD pathology may selectively impact functions of these neocortical regions. The effects of adverse AßPP metabolism in the medial temporal and brainstem regions occur later possibly because of different developmental issues, and the later, different pathology is clearly more cognitively and socially devastating.

The use of standardized uptake values for assessing FDG uptake with PET in oncology: a clinical perspective.

Among clinicians who use positron emission tomography (PET), the standardized uptake value (SUV) is a popular semi-quantitative value that can be easily assessed whenever a PET study is performed under physiological and pathological conditions. It provides an index of regional tracer uptake normalized to the administered dose of tracer. The simplicity of SUV assessment contrasts with the complexity of full quantitative procedures requiring blood sampling and possibly dynamic scanning, which limits patient throughput and significantly increases the workload of a PET centre. Two main clinical conditions/variables affect the significance and usefulness of the SUV: the type and stage of the disease being assessed. Diagnosis, prognosis and therapy monitoring represent the possible uses of SUV. In the above clinical conditions an SUV may provide information about the single lesion in which it is assessed, but the utility of such information depends largely on its integration with all the available clinical and instrumental data.

Normal variations and benign findings in pediatric 18F-FDG-PET/CT.

(18)F-FDG PET and PET/CT have a wide variety of indications in children and young adults. Oncologic indications are the most common, but others include neurology, sports medicine, cardiology, and infection imaging. Accurate interpretation of pediatric (18)F-FDG PET and PET/CT requires a technically adequate study and knowledgeable interpretation of the images. A successful pediatric (18)F-FDG PET requires age-appropriate patient preparation and consideration of patient age and developmental stage. Accurate interpretation of the study requires familiarity with normal patterns of physiologic (18)F-FDG uptake in children at all stages of development.

Effectiveness of individual and group interventions for people with type 2 diabetes / Efetividade das intervenções individual e em grupo junto a pessoas com diabetes tipo 2 / Efectividad de las intervenciones individual y en grupo en personas con diabetes tipo 2

OBJECTIVE: to compare the effectiveness of two educational interventions used by a healthcare provider in the monitoring of individuals with type 2 diabetes mellitus (T2DM), regarding knowledge of the disease, impact on quality of life and adoption of self-care actions. METHODS: comparative, longitudinal, prospective study performed with 150 subjects with type 2 diabetes, analyzed according to the type of participation in the program (individual and/or group). Participants of the individual intervention (II) received nursing consultations every six months and those of the group intervention (GI) took part in weekly meetings for three months. Data were collected through four questionnaires: Identification questionnaire, Problem Areas in Diabetes Questionnaire (PAID), Summary of Diabetes Self-Care Activities Questionnaire (SDSCA) and the Diabetes Knowledge Scale (DKN-A). Data were analyzed using the Friedman and Mann Whitney tests, considering a statistical significance of p ≤ 0.05. RESULTS: there was an increase in knowledge about the disease in the II (p<0.003) and GI (p<0.007), with reduction of the impact on the quality of life in the II (p<0.007) and improvement in self-care actions in the GI (p<0.001). CONCLUSION: in both intervention models improvements were observed in the indicators, over the six month monitoring period. .

OBJETIVO: comparar a efetividade de duas intervenções educativas, utilizadas por uma operadora de saúde, no acompanhamento ao indivíduo com diabetes mellitus Tipo 2 (DM2), quanto ao conhecimento sobre a doença, impacto na qualidade de vida e adoção de ações de autocuidado. MÉTODOS: estudo comparativo, longitudinal, prospectivo, realizado com 150 indivíduos com diabetes tipo 2, analisados conforme a modalidade de participação no programa (individual e/ou em grupo). Os participantes da intervenção individual (II) realizaram consultas de enfermagem a cada seis meses e os da intervenção em grupo (IG), reuniões semanais por três meses. Os dados foram coletados mediante quatro questionários: Questionário de identificação, Questionário de Impacto na Qualidade de Vida em Diabetes (PAID), Questionário de Autocuidado em Diabetes (QAD) e Questionário de Conhecimento do Diabetes (DKN-A). Os dados foram analisados utilizando-se o Teste de Friedman e o Teste de Mann Whitney, considerando significância estatística para p ≤ 0,05. RESULTADOS: verificou-se aumento do conhecimento sobre a doença na II (p<0,003) e na IG (p<0,007), redução do impacto na qualidade de vida na II (p<0,007) e melhora das ações de autocuidado na IG (p<0,001). CONCLUSÃO: em ambos os modelos de intervenção foram observadas melhoras dos indicadores, ao longo dos seis meses de acompanhamento. .

OBJETIVO: comparar la efectividad de dos intervenciones educativas, utilizadas por una operadora de planes de salud, en el acompañamiento al individuo con diabetes mellitus Tipo 2 (DM2), sobre al conocimiento de la enfermedad, impacto en la calidad de vida y adopción de acciones de autocuidado. MÉTODOS: estudio comparativo, longitudinal, prospectivo, realizado con 150 individuos con diabetes tipo 2, analizados conforme la modalidad de participación en el programa (individual y/o en grupo). Los participantes de la intervención individual (II) realizaron consultas de enfermería a cada seis meses y los de intervención en grupo (IG), reuniones semanales por tres meses. Los datos fueron recolectados mediante cuatro cuestionarios: Cuestionario de identificación, Cuestionario de Impacto en la Calidad de Vida en Diabetes (PAID), Cuestionario de Autocuidado en Diabetes (CAD) y Cuestionario de Conocimiento de la Diabetes (DKN-A). Los datos fueron analizados utilizando el test de Friedman y el test de Mann Whitney, considerando significación estadística para p ≤ 0,05. RESULTADOS: se verificó aumento del conocimiento sobre la enfermedad en la II (p<0,003) y en la IG (p<0,007), reducción del impacto en la calidad de vida en la II (p<0,007) y mejoría de las acciones de autocuidado en la IG (p<0,001). CONCLUSIÓN: en los dos modelos de intervención fueron observadas mejorías de los indicadores, a lo largo de los seis meses de acompañamiento. .