Clinical benefits of single vs repeated courses of mesenchymal stem cell therapy in epilepsy patients.

PURPOSE: Epilepsy is defined as "drug-resistant" when existing anti-epileptic drugs (AED) are found to have minimal to no effect on patient's condition. Therefore the search and testing of new treatment strategies is warranted. This study focuses on the effects of autologous mesenchymal stem cells (MSC) in drug-resistant epilepsy patients within a Phase I/II open-label registered clinical trial NCT02497443. MATERIALS/METHODS: A total of 67 patients was included (29 males, 38 females, mean age 33 ± 1.3 yo). The patients received either standard treatment with AEDs, or AEDs supplemented with one or two courses of therapy with autologous bone marrow-derived MSCs expanded in vitro. MSC therapy courses were 6 months apart, and each course consisted of two cell injections: an intravenous infusion of MSCs, followed within 1 week by an intrathecal injection. Primary outcome of the study was safety, secondary outcome was efficacy in terms of seizure frequency reduction and response to treatment. RESULTS: MSC injections proved safe and did not cause any severe side effects. In MSC group (n = 34), 61.7% patients responded to therapy at 6 months timepoint (p < 0.01 vs control, n = 33), and the number rose to 76.5% by 12 months timepoint. Decrease in anxiety and depression scores and paroxysmal epileptiform activity was observed in MSC group based on HADS and EEG, respectively, and MMSE score has also improved. Another observation was that concomitant administration of levetiracetam, but not other AEDs, correlated significantly with the success of MSC therapy. Second course of MSC therapy facilitated further reduction in seizure count and epileptiform EEG activity (p < 0.05 vs single course). CONCLUSIONS: Application of autologous mesenchymal stem cell-based therapy in patients with pharmacoresistant epilepsy demonstrated significant anticonvulsant potential. This effect lasted for at least 1 year, with repeated administration of MSCs conveying additional clinical benefit.

Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study.

PURPOSE: Existing anti-epileptic drugs (AED) have limited efficiency in many patients, necessitating the search for alternative approaches such as stem cell therapy. We report the use of autologous patient-derived mesenchymal stem cells (MSC) as a therapeutic agent in symptomatic drug-resistant epilepsy in a Phase I open label clinical trial (registered as NCT02497443). PATIENTS AND METHODS: The patients received either standard treatment with AED (control group), or AED supplemented with single intravenous administration of undifferentiated autologous MSC (target dose of 1×106cells/kg), followed by a single intrathecal injection of neurally induced autologous MSC (target dose of 0.1×106cells/kg). RESULTS: MSC injections were well tolerated and did not cause any severe adverse effects. Seizure frequency was designated as the main outcome and evaluated at 1 year time point. 3 out of 10 patients in MSC therapy group achieved remission (no seizures for one year and more), and 5 additional patients became responders to AEDs, while only 2 out of 12 patients became responders in control group (difference significant, P=0.0135). CONCLUSIONS: MSC possess unique immunomodulatory properties and are a safe and promising candidate for cell therapy in AED resistant epilepsy patients.

Radiotherapy staffing in the European countries: final results from the ESTRO-HERO survey.

BACKGROUND: The ESTRO Health Economics in Radiation Oncology (HERO) project has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The first milestone was to assess the availability of radiotherapy resources within Europe. This paper presents the personnel data collected in the ESTRO HERO database. MATERIALS AND METHODS: An 84-item questionnaire was sent out to European countries, through their national scientific and professional radiotherapy societies. The current report includes a detailed analysis of radiotherapy staffing (questionnaire items 47-60), analysed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis was conducted between February and July 2014, and is based on validated responses from 24 of the 40 European countries defined by the European Cancer Observatory (ECO). RESULTS: A large variation between countries was found for most parameters studied. Averages and ranges for personnel numbers per million inhabitants are 12.8 (2.5-30.9) for radiation oncologists, 7.6 (0-19.7) for medical physicists, 3.5 (0-12.6) for dosimetrists, 26.6 (1.9-78) for RTTs and 14.8 (0.4-61.0) for radiotherapy nurses. The combined average for physicists and dosimetrists is 9.8 per million inhabitants and 36.9 for RTT and nurses. Radiation oncologists on average treat 208.9 courses per year (range: 99.9-348.8), physicists and dosimetrists conjointly treat 303.3 courses (range: 85-757.7) and RTT and nurses 76.8 (range: 25.7-156.8). In countries with higher GNI per capita, all personnel categories treat fewer courses per annum than in less affluent countries. This relationship is most evident for RTTs and nurses. Different clusters of countries can be distinguished on the basis of available personnel resources and socio-economic status. CONCLUSIONS: The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes.

Guidelines for equipment and staffing of radiotherapy facilities in the European countries: final results of the ESTRO-HERO survey.

BACKGROUND AND PURPOSE: In planning to meet evidence based needs for radiotherapy, guidelines for the provision of capital and human resources are central if access, quality and safety are not to be compromised. A component of the ESTRO-HERO (Health Economics in Radiation Oncology) project is to document the current availability and content of guidelines for radiotherapy in Europe. MATERIALS AND METHODS: An 84 part questionnaire was distributed to the European countries through their national scientific and professional radiotherapy societies with 30 items relating to the availability of guidelines for equipment and staffing and selected operational issues. Twenty-nine countries provided full or partial evaluable responses. RESULTS: The availability of guidelines across Europe is far from uniform. The metrics used for capital and human resources are variable. There seem to have been no major changes in the availability or specifics of guidelines over the ten-year period since the QUARTS study with the exception of the recent expansion of RTT staffing models. Where comparison is possible it appears that staffing for radiation oncologists, medical physicists and particularly RTTs tend to exceed guidelines suggesting developments in clinical radiotherapy are moving faster than guideline updating. CONCLUSION: The efficient provision of safe, high quality radiotherapy services would benefit from the availability of well-structured guidelines for capital and human resources, based on agreed upon metrics, which could be linked to detailed estimates of need.

Radiotherapy equipment and departments in the European countries: final results from the ESTRO-HERO survey.

BACKGROUND: Documenting the distribution of radiotherapy departments and the availability of radiotherapy equipment in the European countries is an important part of HERO - the ESTRO Health Economics in Radiation Oncology project. HERO has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The aim of the current report is to describe the distribution of radiotherapy equipment in European countries. METHODS: An 84-item questionnaire was sent out to European countries, principally through their national societies. The current report includes a detailed analysis of radiotherapy departments and equipment (questionnaire items 26-29), analyzed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis is based on validated responses from 28 of the 40 European countries defined by the European Cancer Observatory (ECO). RESULTS: A large variation between countries was found for most parameters studied. There were 2192 linear accelerators, 96 dedicated stereotactic machines, and 77 cobalt machines reported in the 27 countries where this information was available. A total of 12 countries had at least one cobalt machine in use. There was a median of 0.5 simulator per MV unit (range 0.3-1.5) and 1.4 (range 0.4-4.4) simulators per department. Of the 874 simulators, a total of 654 (75%) were capable of 3D imaging (CT-scanner or CBCT-option). The number of MV machines (cobalt, linear accelerators, and dedicated stereotactic machines) per million inhabitants ranged from 1.4 to 9.5 (median 5.3) and the average number of MV machines per department from 0.9 to 8.2 (median 2.6). The average number of treatment courses per year per MV machine varied from 262 to 1061 (median 419). While 69% of MV units were capable of IMRT only 49% were equipped for image guidance (IGRT). There was a clear relation between socio-economic status, as measured by GNI per capita, and availability of radiotherapy equipment in the countries. In many low income countries in Southern and Central-Eastern Europe there was very limited access to radiotherapy and especially to equipment for IMRT or IGRT. CONCLUSIONS: The European average number of MV machines per million inhabitants and per department is now better in line with QUARTS recommendations from 2005, but the survey also showed a significant heterogeneity in the access to modern radiotherapy equipment in Europe. High income countries especially in Northern-Western Europe are well-served with radiotherapy resources, other countries are facing important shortages of both equipment in general and especially machines capable of delivering high precision conformal treatments (IMRT, IGRT).