Evaluation of the Implementation of the Response Assessment in Neuro-Oncology Criteria in the HERBY Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

BACKGROUND AND PURPOSE: HERBY was a Phase II multicenter trial setup to establish the efficacy and safety of adding bevacizumab to radiation therapy and temozolomide in pediatric patients with newly diagnosed non-brain stem high-grade gliomas. This study evaluates the implementation of the radiologic aspects of HERBY. MATERIALS AND METHODS: We analyzed multimodal imaging compliance rates and scan quality for participating sites, adjudication rates and reading times for the central review process, the influence of different Response Assessment in Neuro-Oncology criteria in the final response, the incidence of pseudoprogression, and the benefit of incorporating multimodal imaging into the decision process. RESULTS: Multimodal imaging compliance rates were the following: diffusion, 82%; perfusion, 60%; and spectroscopy, 48%. Neuroradiologists' responses differed for 50% of scans, requiring adjudication, with a total average reading time per patient of approximately 3 hours. Pseudoprogression occurred in 10/116 (9%) cases, 8 in the radiation therapy/temozolomide arm and 2 in the bevacizumab arm (P < .01). Increased target enhancing lesion diameter was a reason for progression in 8/86 cases (9.3%) but never the only radiologic or clinical reason. Event-free survival was predicted earlier in 5/86 (5.8%) patients by multimodal imaging (diffusion, n = 4; perfusion, n = 1). CONCLUSIONS: The addition of multimodal imaging to the response criteria modified the assessment in a small number of cases, determining progression earlier than structural imaging alone. Increased target lesion diameter, accounting for a large proportion of reading time, was never the only reason to designate disease progression.

Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

Determination of tumor response to treatment in neuro-oncology is challenging, particularly when antiangiogenic agents are considered. Nontumoral factors (eg, blood-brain barrier disruption, edema, and necrosis) can alter contrast enhancement independent of true tumor response/progression. Furthermore, gliomas are often infiltrative, with nonenhancing components. In adults, the Response Assessment in Neuro-Oncology (RANO) criteria attempted to address these issues. No such guidelines exist yet for children. The ongoing randomized phase II trial, A Study of Avastin (bevacizumab) in Combination With Temolozomide (TMZ) and Radiotherapy in Paediatric and Adolescent Patients With High-Grade Glioma (HERBY), will establish the efficacy and safety of the antiangiogenic agent bevacizumab for the first-line treatment of newly diagnosed high-grade glioma in children (n = 121 patients, enrollment complete). The primary end point is event-free survival (tumor progression/recurrence by central review, second primary malignancy, or death). Determination of progression or response is based on predefined clinical and radiographic criteria, modeled on the RANO criteria and supported by expert pseudoprogression review and the use of standardized imaging protocols. The HERBY trial will also compare conventional MR imaging (T1-weighted and T2/fluid-attenuated inversion recovery sequences) with conventional MR imaging plus diffusion/perfusion imaging for response assessment. It is anticipated that HERBY will provide new insights into antiangiogenic-treated pediatric brain tumors. HERBY will also investigate the practicality of obtaining adequate quality diffusion/perfusion scans in a trial setting, and the feasibility of implementing standard imaging protocols across multiple sites. To date, 61/73 (83.6%) patients with available data have completed diffusion-weighted imaging (uptake of other nonconventional techniques has been limited). Harmonization of imaging protocols and techniques may improve the robustness of pediatric neuro-oncology studies and aid future trial comparability.

Quality assurance for diabetic retinopathy telescreening.

AIMS: TOSCA was an EU-Commission supported international research project designed to develop telescreening services in diabetic retinopathy and glaucoma. This paper describes the quality assurance methods developed for the diabetic retinopathy telescreening service within the TOSCA project. SETTING: The study was performed in 1895 patients with diabetes between 2000 and 2002 at diabetic retinopathy screening sites in five European countries. Data were analysed centrally. METHODS: Patients attending each clinic's diabetic retinopathy screening service received standardized retinal photography. The images and associated data were transferred electronically to a remote location for grading. Each photographer uploading images and each grader downloading images for assessment was controlled by a systematic quality management approach. The quality assurance measures defined were image quality, intragrader reliability. A cockpit chart was developed for the management and presentation of relevant results and quality measures. For the intragrader reliability tests, 10% of the images were processed for a second grading. An algorithm for calculating differences between repeated gradings was developed. RESULTS: The assessment of image quality for the different sites showed that only 0-0.7% were unassessable. One hundred per cent agreement for both gradings was achieved in 50-85% of graded cases, depending on site and grader, and an agreement better than 95% in 71-100% of cases. CONCLUSIONS: A telemedicine-supported quality assurance process is practical and advantageous. The cockpit charts have proven to be useful tools when monitoring the performance of a telescreening service. Grader feedback showed high satisfaction with the quality assurance process.

Impact of virtual reality imaging on hepatic liver tumor resection: calculation of risk.

The risk involved in partial liver resections depends mainly on tumor localization, invasion of central vascular structures, and parenchymal function. The imaging techniques available today (computed tomography, magnetic resonance imaging) allow us to detect precisely the extent of tumor invasion and their relationship to central vessels. The various three-dimensional reconstruction techniques are helpful with regard to a virtual planning of liver resections. The calculation of remaining liver volumes subsequent to partial hepatectomies are considered to be an essential predictive parameter in terms for the development of postoperative liver failure. In a retrospective and a later consecutive, prospective clinical study we analyzed the postoperative risk in a series of 570 patients. In an univariate analysis 13 of 31 parameters showed significant values. In multivariate analysis only three parameters (partial hepatic resection rate, PHRR), gamma-glutamyltranspeptidase, and prothrombin activity) were independent parameters for predicting liver failure, generating the most significant values for the PHRR. In our experience the most comfortable and precise technique for evaluating PHRR is the b-spline technique.

Evaluation of telemedical services.

With the rapidly increasing development of telemedicine technology, the evaluation of telemedical services becomes more and more important. However, professional views of the aims and methods of evaluation are different from the perspective of computer science and engineering or from medicine and health policy. We propose that a continuous evaluation strategy should be chosen which guides the development and implementation of telemedicine technologies and applications. The evaluation strategy is divided into four phases in which the focus of evaluation is shifted from technical performance of the system in the early phases to medical outcome criteria and economical aspects in later phases. We review the study design methodology established for clinical trials assessing therapeutic effectiveness and diagnostic accuracy and discuss how it can be adapted to evaluation studies in telemedicine. As an example, we describe our approach to evaluation in a teleconsultation network in ophthalmology.

[Teleconsultation network for ophthalmology--experiences and results]. / Telekonsultationsnetzwerk für die Ophthalmologie--Erfahrungen und Ergebnisse.

MOTIVATION: Telemedical services for ophthalmology are developed within the OPHTEL project, which has been funded by the European Union and by the Bavarian government in the Bavaria-online initiative. METHODS: Seven private ophthalmologists, one university eye clinic, one clinical Diabetes center and an informatics research institute are connected within a teleconsultation network. Asynchronous (based on Internet E-Mail) and synchronous (based on ISDN-mediated videoconferencing tools) types of teleconsultations are realized. RESULTS: 86 teleconsultations (62 asynchronous, 23 synchronous) took place within the first 10 months. Complex and rare eye diseases as well as interdisciplinary questions (ophthalmology--diabetology) are the main area of medical communication interest. Legal and security problems are discussed. CONCLUSIONS: Telemedical services must be understood as a complete process of medical care on the basis of modern communication technologies, which influences also the management of this process.

[Scientific role of German ophthalmology in the European telecommunication project OPHTEL]. / Wissenschaftliche Rolle der deutschen Ophthalmologie im europäischen Telekommunikationsprojekt OPHTEL.

BACKGROUND: In Denmark, France, Germany, Great Britain and Italy, the OPHTEL project combines clinical centers of ophthalmology and internal medicine, an institute for medical informatics and health services research, a publishing company and different industrial partners in the EDP market. AIMS: With the aid of visual telecommunication and rapid data transfer, methods and conditions will be developed and proved so that any physician can very easily obtain sufficient information for treating his patient. Thus, the regional differences in the quality of structured health service (e.g., urban/ rural) will be overcome throughout Europe. SCIENTIFIC TASKS: A multilingual diagnostic and therapeutic thesaurus has to be worked out in order to create standards for communication and quality control. Based on literature, images and image analysis in a knowledge-based data bank, a monitoring system (containing watch-dog functions) and the basic aspects of an ophthalmological patient/disease register will be investigated. (In parallel, a technical development of synchronous and asynchronous telecommunication between eye physicians is taking place in close cooperation with the regional Bavarian project Teleopathalmology in Bavaria on-line). RESULTS: State of the art 6 months after starting the project:the knowledge-based image data bank has been founded and also an ophthalmological 8 language thesaurus and definition standard. All data transfer lines are installed. DISCUSSION: The project is taking place amid diverging sections of medicine: ophthalmology and internal medicine, health politics and data protection, individual treatment and common interest (health care), product management and office organization. Thus, the scientific quality of the transferred ophthalmological content must undergo sophisticated controls. FUTURE STEPS: Intense cooperation with the big German associations for ophthalmology (DOG, BVA) and the European ophthalmological societies concerning EDP, classification and quality control.