| 1. |
- Journeau, C., et al.
(författare)
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European Research on the Corium issues within the SARNET network of excellence
- 2008
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Ingår i: International Conference on Advances in Nuclear Power Plants, ICAPP 2008. - 9781605607870 ; , s. 1172-1181
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Konferensbidrag (refereegranskat)abstract
- Within SARNET, the corium topic covers all the behaviors of corium from early phase of core degradation to in or ex-vessel corium recovery with the exception of corium interaction with water, direct containment heating and fission product release. The corium topic regroups in three work packages the critical mass of competence required to improve significantly the corium behavior knowledge. The spirit of the SARNET networking is to share the knowledge, the facilities and the simulation tools for severe accidents, so to reach a better efficiency and to rationalize the R&D effort at European level. Extensive benchmarking has been launched in most of the areas of research. These benchmarks were mainly dedicated to the recalculation of experiments, while, in the next periods, a larger focus will be given to integral experiments or reactor applications. Eventually, all the knowledge will be accumulated in the ASTEC severe accident simulation code through physical model improvements and extension of validation database. This paper summarizes the progress that has been achieved in the frame of the networking activities. A special focus is placed on the melt pool and debris coolability and corium-concrete interaction, in which, the effects due to multidimensional geometries and heterogeneities has been shown, during SARNET, to play a crucial role and for which further research is still needed.
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| 2. |
- Parker, C., et al.
(författare)
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Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:3, s. 213-223
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Tidskriftsartikel (refereegranskat)abstract
- Background Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. Methods In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. Results At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. Conclusions In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.)
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| 12. |
- Greimel, E, et al.
(författare)
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An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQ-OV28) in assessing the quality of life of patients with ovarian cancer.
- 2003
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Ingår i: European journal of cancer (Oxford, England : 1990). - 0959-8049. ; 39:10, s. 1402-8
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Tidskriftsartikel (refereegranskat)abstract
- This study defines the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) quality of life (QOL) questionnaire designed to measure the QOL of patients with ovarian cancer. The ovarian cancer module (EORTC QLQ-OV28) was developed to supplement the EORTC QLQ-C30. The core questionnaire and the QLQ-OV28 were prospectively administered to 368 ovarian cancer patients after they had been treated with radical or debulking surgery followed by chemotherapy. The QLQ-OV28 module assesses abdominal/gastrointestinal symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal/menopausal symptoms, body image, attitude to disease/treatment and sexual functioning. Questionnaires were well accepted by patients, baseline compliance rates were 86%, 72% provided a second assessment, less than 3% of the items had missing data. Multi-trait scaling analyses confirmed the hypothesised scales. All hypothesised scales exhibited good psychometric properties. These results support the clinical and psychometric validity of the EORTC QLQ-OV28 module as a supplement to the EORTC QLQ-C30.
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| 13. |
- Journeau, C., et al.
(författare)
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Safest roadmap for corium experimental research in Europe
- 2018
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Ingår i: ASCE-ASME J of Risk & Uncertainty in Engineering Systems Part B. - : ASME Press. - 2332-9017 .- 2332-9025. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Severe accident facilities for European safety targets (SAFEST) is a European project networking the European experimental laboratories focused on the investigation of a nuclear power plant (NPP) severe accident (SA) with reactor core melting and formation of hazardous material system known as corium. The main objective of the project is to establish coordinated activities, enabling the development of a common vision and severe accident research roadmaps for the next years, and of the management structure to achieve these goals. In this frame, a European roadmap on severe accident experimental research has been developed to define research challenges to contribute to further reinforcement of Gen II and III NPP safety. The roadmap takes into account different SA phenomena and issues identified and prioritized in the analyses of severe accidents at commercial NPPs and in the results of the recent European stress tests carried out after the Fukushima accident. Nineteen relevant issues related to reactor core meltdown accidents have been selected during these efforts. These issues have been compared to a survey of the European SA research experimental facilities and corium analysis laboratories. Finally, the coherence between European infrastructures and R&D needs has been assessed and a table linking issues and infrastructures has been derived. The comparison shows certain important lacks in SA research infrastructures in Europe, especially in the domains of core late reflooding impact on source term, reactor pressure vessel failure and molten core release modes, spent fuel pool (SFP) accidents, as well as the need for a large-scale experimental facility operating with up to 500 kg of chemically prototypic corium melt.
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| 17. |
- Weis, J., et al.
(författare)
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Sensitivity to change of the EORTC quality of life module measuring cancer-related fatigue (EORTC QlQ-Fa12): Results from the international psychometric validation
- 2019
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Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 28, s. 1753-1761
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Tidskriftsartikel (refereegranskat)abstract
- Objective The European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) has developed a multidimensional instrument measuring cancer-related fatigue, the EORTC QLQ-FA12. The analysis of sensitivity to change is an essential part of psychometric validation. With this study, we investigated the EORTC QLQ-FA12's sensitivity to change. Methods The methodology follows the EORTC guidelines of EORTC QLG for phase IV validation of modules. We included cancer patients undergoing curative and palliative treatment at t1 and followed them up prospectively over the course of their treatment (t2) and 4 weeks after completion of treatment (t3). Data were collected prospectively at 17 sites in 11 countries. Sensitivity to change was investigated using analysis of variance. Results A total sample of 533 patients was enrolled with various tumour types, different stages of cancer, and receiving either curative treatment (n=311) or palliative treatment (n=222). Over time all fatigue scores were significantly higher in the palliative treatment group compared with the curative group (p < .001). Physical fatigue increased with medium effect size over the course of treatment in the curative group (standardized response mean [SRM] (t1,t2) = 0.44]. After treatment physical [SRM (t2,t3) = 0.39], emotional [SRM (t2,t3)= 0.28] and cognitive fatigue (SRM [t2,t3] = 0.22) declined significantly in the curative group. In the palliative group, emotional (SRM [t2,t3] = 0.18) as well as cognitive [SRM [t2,t3] = 0.26) fatigue increases significantly. Conclusions The EORTC-QLQ-FA12 proved to identify clinically significant changes in fatigue in the course of curative and palliative cancer treatment.
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| 19. |
- Bottomley, D., et al.
(författare)
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Severe accident research in the core degradation area : An example of effective international cooperation between the European Union (EU) and the Commonwealth of Independent States (CIS) by the International Science and Technology Center
- 2012
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Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 252, s. 226-241
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Tidskriftsartikel (refereegranskat)abstract
- The International Science and Technology Center (ISTC) was set up in Moscow to support non-proliferation of sensitive knowledge and technologies in biological, chemical and nuclear domains by engaging scientists in peaceful research programmes with a broad international cooperation. The paper has two following objectives: to describe the organization of complex, international, experimental and analytical research of material processes under extreme conditions similar to those of severe accidents in nuclear reactors and, to inform briefly about some results of these studies. The main forms of ISTC activity are Research Projects and Supporting Programs. In the Research Projects informal contact expert groups (CEGs) were set up by ISTC to improve coordination between adjacent projects and to encourage international collaboration. The European Commission was the first to use this. The CEG members - experts from the national institutes and industry - evaluated and managed the projects' scientific results from initial stage of proposal formulation until the final reporting. They were often involved directly in the project's details by joining the Steering Committees of the project. The Contact Expert Group for Severe Accidents and Management (CEG-SAM) is one of these groups, five project groups from this area from the total of 30 funded projects during 10 years of activity are detailed to demonstrate this: (1) QUENCH-VVER from RIAR, Dimitrovgrad and IBRAE, Moscow, and PARAMETER projects (SF1-SF4) from LUCH, Podolsk and IBRAE, Moscow; these concerned a detailed study of bundle quenching from high temperature; (2) Reactor Core Degradation; a modelling project simulating the fuel rod degradation and loss of geometry from IBRAE, Moscow; (3) METCOR projects from NITI, St. Petersburg on the interaction of core melt with reactor vessel steel; (4) INVECOR project, NNE Kurchatov City, Kazakhstan; this is a large-scale facility to examine the vessel steel retention of 60 kg corium during the decay heat; and finally, (5) CORPHAD and PRECOS projects, NITI, St. Petersburg undertook a systematic examination of refractory ceramics relevant to in-vessel and ex-vessel coria, particularly examining poorly characterised, limited data or experimentally difficult systems.
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| 22. |
- Coomans, Marijke B., et al.
(författare)
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Measuring change in health-related quality of life: the impact of different analytical methods on the interpretation of treatment effects in glioma patients
- 2020
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Ingår i: Neuro-Oncology Practice. - : OXFORD UNIV PRESS. - 2054-2577 .- 2054-2585. ; 7:6, s. 668-675
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Tidskriftsartikel (refereegranskat)abstract
- Background. Different analytical methods may lead to different conclusions about the impact of treatment on health-related quality of life (HRQoL). This study aimed to examine 3 different methods to evaluate change in HRQoL and to study whether these methods result in different conclusions. Methods. HRQoL data from 15 randomized clinical trials were combined (CODAGLIO project). Change in HRQoL scores, measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and BN20 questionnaires, was analyzed in 3 ways: (1) at the group level, comparing mean changes in scale/item scores between treatment arms, (2) at the patient level per scale/item, calculating the percentage of patients that deteriorated, improved, or remained stable per scale/item, and (3) at the individual patient level, combining all scales/items. Results. Baseline and first follow-up HRQoL data were available for 3727 patients. At the group scale/item level, only the item "hair loss" showed a significant and clinically relevant change (ie, >= 10 points) over time, whereas change scores on the other scales/items were statistically significant only (all P <.001; range in change score, 0.1-6.2). Although a large proportion of patients had stable HRQoL over time (range, 27%-84%) on the patient level per scale/item, many patients deteriorated (range, 6%-43%) or improved (range, 8%-32%) on a specific scale/item. At the individual patient level, the majority of patients (86%) showed both deterioration and improvement, whereas only 1% remained stable on all scales. Conclusions. Different analytical methods of changes in HRQoL result in distinct conclusions of treatment effects, all of which may be relevant for informing clinical decision making.
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| 23. |
- Coomans, Marijke B., et al.
(författare)
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Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?
- 2019
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Ingår i: Neuro-Oncology. - : OXFORD UNIV PRESS INC. - 1522-8517 .- 1523-5866. ; 21:11, s. 1447-1457
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Tidskriftsartikel (refereegranskat)abstract
- Background. Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients functioning. Methods. Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders. Results. Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5-10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (amp;gt;= 10 points difference) physical, role, and social functioning (betas ranged from -11.3 to -15.9, all P amp;lt; 0.001), independent of other factors. Similarly, having symptoms in the fatigue cluster was found to negatively influence role functioning (beta of -12.3, P amp;lt; 0.001), independent of other factors. Conclusions. Two symptom clusters, the fatigue and motor cluster, were frequently affected in glioma patients and were found to independently have a negative association with certain aspects of patients functioning as measured with a self-report questionnaire.
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| 24. |
- Coomans, Marijke, et al.
(författare)
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Factors associated with health-related quality of life (HRQoL) deterioration in glioma patients during the progression-free survival period
- 2022
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 24:12, s. 2159-2169
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Tidskriftsartikel (refereegranskat)abstract
- Background Maintenance of functioning and well-being during the progression-free survival (PFS) period is important for glioma patients. This study aimed to determine whether health-related quality of life (HRQoL) can be maintained during progression-free time, and factors associated with HRQoL deterioration in this period. Methods We included longitudinal HRQoL data from previously published clinical trials in glioma. The percentage of patients with stable HRQoL until progression was determined per scale and at the individual patient level (i.e. considering all scales simultaneously). We assessed time to a clinically relevant deterioration in HRQoL, expressed in deterioration-free survival and time-to-deterioration (the first including progression as an event). We also determined the association between sociodemographic and clinical factors and HRQoL deterioration in the progression-free period. Results Five thousand five hundred and thirty-nine patients with at least baseline HRQoL scores had a median time from randomization to progression of 7.6 months. Between 9-29% of the patients deteriorated before disease progression on the evaluated HRQoL scales. When considering all scales simultaneously, 47% of patients deteriorated on >= 1 scale. Median deterioration-free survival period ranged between 3.8-5.4 months, and median time-to-deterioration between 8.2-11.9 months. For most scales, only poor performance status was independently associated with clinically relevant HRQoL deterioration in the progression-free period. Conclusions HRQoL was maintained in only 53% of patients in their progression-free period, and treatment was not independently associated with this deterioration in HRQoL. Routine monitoring of the patients functioning and well-being during the entire disease course is therefore important, so that interventions can be initiated when problems are signaled.
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| 25. |
- Coomans, Marijke, et al.
(författare)
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The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials
- 2019
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Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 116, s. 190-198
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small. (C) 2019 Elsevier Ltd. All rights reserved.
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| 28. |
- Khabensky, V. B., et al.
(författare)
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Effect of temperature gradient on chemical element partitioning in corium pool during in-vessel retention
- 2018
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Ingår i: Nuclear Engineering and Design. - : Elsevier Ltd. - 0029-5493 .- 1872-759X. ; 327, s. 82-91
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Tidskriftsartikel (refereegranskat)abstract
- The paper presents some results of the ISTC (International Science and Technology Center)-financed project ‘Investigation of Corium Melt Interaction with NPP Reactor Vessel Steel’ (METCOR). In the METCOR experiments the metallic phase of a two-liquid system was produced by the interaction between hot suboxidized corium and cooled VVER vessel steel, with the steel being corroded. Models of corrosion mechanisms in the considered conditions are used to systematize data on the limiting temperature of corrosion/(dissolution) of the vessel steel. A considerable influence of thermal gradient conditions is shown, which has to be taken into account in the analysis of molten pool behaviour.
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| 30. |
- Musoro, ZJ, et al.
(författare)
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Establishing anchor-based minimally important differences (MID) with the EORTC quality-of-life measures: a meta-analysis protocol
- 2018
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:1, s. e019117-
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Tidskriftsartikel (refereegranskat)abstract
- As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated.Methods and analysisData will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for different cancer sites separately. Focus is on anchor-based methods. Anchors will be selected per disease site from available data. A disease-oriented and methodological panel will provide independent guidance on anchor selection. We aim to construct multiple clinical anchors per QLQ-C30 scale and also to compare with several anchor-based methods. The effects of covariates, for example, gender, age, disease stage and so on, will also be investigated. We will examine how our estimated MIDs compare with previously published guidelines, hence further contributing to robust MID guidelines for the EORTC QLQ-C30.Ethics and disseminationAll patient data originate from completed clinical trials with mandatory written informed consent, approved by local ethical committees. Our findings will be presented at scientific conferences, disseminated via peer-reviewed publications and also compiled in a MID ‘blue book’ which will be made available online on the EORTC Quality of Life Group website as a free guideline document.
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| 31. |
- Parker, Christopher C., et al.
(författare)
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Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial
- 2018
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 73:3, s. 427-435
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Tidskriftsartikel (refereegranskat)abstract
- Background: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. Objective: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. Design, setting, and participants: Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving >= 1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk after the last study-drug injection, to 3 yr from the first injection. Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. Outcome measurements and statistical analysis: All adverse events (AEs) were collected until 12 wk after the last injection; subsequently, only treatment-related AEs were collected. Additional long-term safety was assessed by development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and secondary malignancies. Data analysis used descriptive statistics. Results and limitations: During treatment to 12 wk following the last injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 mo after the last injection. No other cases were observed. Limitations include short (3-yr) follow-up. Conclusions: Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns.
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| 33. |
- Reijneveld, Jaap C, et al.
(författare)
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Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033) : a randomised, open-label, phase 3 intergroup study.
- 2016
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 17:11, s. 1533-1542
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Temozolomide chemotherapy versus radiotherapy in patients with a high-risk low-grade glioma has been shown to have no significant effect on progression-free survival. If these treatments have a different effect on health-related quality of life (HRQOL), it might affect the choice of therapy. We postulated that temozolomide compromises HRQOL and global cognitive functioning to a lesser extent than does radiotherapy.METHODS: We did a prospective, phase 3, randomised controlled trial at 78 medical centres and large hospitals in 19 countries. We enrolled adult patients (aged ≥18 years) with histologically confirmed diffuse (WHO grade II) astrocytoma, oligodendroglioma, or mixed oligoastrocytoma, with a WHO performance status of 2 or lower, without previous chemotherapy or radiotherapy, who needed active treatment other than surgery. We randomly assigned eligible patients (1:1) using a minimisation technique, stratified by WHO performance status (0-1 vs 2), age (<40 years vs ≥40 years), presence of contrast enhancement on MRI, chromosome 1p status (deleted vs non-deleted vs indeterminate), and the treating medical centre, to receive either radiotherapy (50·4 Gy in 28 fractions of 1·8 Gy for 5 days per week up to 6·5 weeks) or temozolomide chemotherapy (75 mg/m(2) daily, for 21 of 28 days [one cycle] for 12 cycles). The primary endpoint was progression-free survival (results published separately); here, we report the results for two key secondary endpoints: HRQOL (assessed using the European Organisation for Research and Treatment of Cancer's [EORTC] QLQ-C30 [version 3] and the EORTC Brain Cancer Module [QLQ-BN20]) and global cognitive functioning (assessed using the Mini-Mental State Examination [MMSE]). We did analyses on the intention-to-treat population. This study is closed and is registered at EudraCT, number 2004-002714-11, and at ClinicalTrials.gov, number NCT00182819.FINDINGS: Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 eligible patients to either radiotherapy (n=240) or temozolomide chemotherapy (n=237). The difference in HRQOL between the two treatment groups was not significant during the 36 months' follow-up (mean between group difference [averaged over all timepoints] 0·06, 95% CI -4·64 to 4·75, p=0·98). At baseline, 32 (13%) of 239 patients who received radiotherapy and 32 (14%) of 236 patients who received temozolomide chemotherapy had impaired cognitive function, according to the MMSE scores. After randomisation, five (8%) of 63 patients who received radiotherapy and three (6%) of 54 patients who received temozolomide chemotherapy and who could be followed up for 36 months had impaired cognitive function, according to the MMSE scores. No significant difference was recorded between the groups for the change in MMSE scores during the 36 months of follow-up.INTERPRETATION: The effect of temozolomide chemotherapy or radiotherapy on HRQOL or global cognitive functioning did not differ in patients with low-grade glioma. These results do not support the choice of temozolomide alone over radiotherapy alone in patients with high-risk low-grade glioma.FUNDING: Merck Sharp & Dohme-Merck & Co, National Cancer Institute, Swiss Cancer League, National Institute for Health Research, Cancer Research UK, Canadian Cancer Society Research Institute, National Health and Medical Research Council, European Organisation for Research and Treatment of Cancer Cancer Research Fund.
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| 35. |
- Taphoorn, Martin J. B., et al.
(författare)
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Health-Related Quality of Life in a Randomized Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma
- 2015
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 33:19, s. 2166-U205
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Tidskriftsartikel (refereegranskat)abstract
- Purpose As glioblastoma progresses, patients experience a decline in health-related quality of life (HRQoL). Delaying this decline is an important treatment goal. In newly diagnosed glioblastoma, progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide (RT/TMZ) versus placebo plus RT/TMZ (phase III AVAglio study; hazard ratio, 0.64; 95% CI, 0.55 to 0.74; P < .001). To ensure that addition of bevacizumab to standard-of-care therapy was not associated with HRQoL detriment, HRQoL assessment was a secondary objective. Patients and Methods Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BN20 at each tumor assessment (Appendix Table A1, online only). Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated (stable: < 10-point change; clinically relevant deterioration/improvement: 10-point change). Deterioration-free survival was the time to deterioration/progression/death; time to deterioration was the time to deterioration/death. Results Most evaluable patients who had not progressed (> 74%) completed all HRQoL assessments for at least 1 year of treatment, and almost all completed at least one HRQoL assessment at baseline (98.3% and 97.6%, bevacizumab and placebo arms, respectively). Mean changes from baseline did not reach a clinically relevant difference between arms for most items. HRQoL declined at progression in both arms. The addition of bevacizumab to RT/TMZ resulted in statistically longer (P < .001) deterioration-free survival across all items. Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm (v bevacizumab) for any HRQoL item. Conclusion The addition of bevacizumab to standard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period.
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