La radioterapia en las enfermedades no malignas del aparato locomotor

Los autores hacen una revisión de las indicaciones y resultados obtenidos mediante la radioterapia en enfermedades del aparato locomotor, excluyendo las enfermedades proliferativas malignas. En el ámbito de los procesos inflamatorios siguen existiendo dudas a su eficacia en el tratamiento de bursitis y tendinitis, por el contrario, tanto en el tratamiento sistémico inmunosupresor de la artritis reumatoide como en la formación heterotópica de hueso, su utilidad está probada. En el campo de los procesos proliferativos no malignos, el papel de la radioterapia es indudable. Los tumores desmoides o fibromatosis agresiva, el ameloblastoma, los quistes óseos aneurismáticos, los hemangiomas óseos en general y vertebrales en particular, así como en la sinovitis vellonodular pigmentada, la radioterapia, administra tras la cirugía o como tratamiento exclusivo en los enfermos inoperables o antes una recidiva es el tratamiento de elección. En el trabajo se exponen las posibles áreas de colaboración entre radioterapeutas y reumatólogo, ortopedas, traumatólogos y rehabilitadores.The Authors present a critical review of the indications and results of radiotherapy in the treatment of non-malignant diseases of the musculoskeletal system. In inflamatory disorders, there are still controversias in the treatment of bursitis and tendinitis, whereas for immunosuppression in rheumatoid arthritis and heterotopic ossification alter total hip replacemente, the indications of radiotherapy are well established. In non-malignant proliferative diseases, the role of ionizing radiation is clear. Aggressive fibromatosis, ameblastoma, aneurystmal bone cyst, haemangiomas, and pigmented villonodular synovitis, radiotherapy, associated with surgical procedures or as an exclusive treatment in inoperable or relapsed patient, is the treatment of choice

Refining critical structure contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark results and consensus guidelines from the STOPSTORM.eu consortium

Background and purpose: In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM.eu consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. Materials and methods: Centres within the STOPSTORM.eu consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). Results: Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC = 0.96, median MDA = 0.1 mm and median HD95 = 1.1 mm) and aorta (median DSC = 0.90, median MDA = 0.1 mm and median HD95 = 1.5 mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC = 0.83, median MDA = 0.2 mm and median HD95 = 0.5 mm), valves (median DSC = 0.16, median MDA = 4.6 mm and median HD95 = 16.0 mm), coronary arteries (median DSC = 0.4, median MDA = 0.7 mm and median HD95 = 8.3 mm) and the sinoatrial and atrioventricular nodes (median DSC = 0.29, median MDA = 4.4 mm and median HD95 = 11.4 mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. Conclusion: This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established.The authors would like to thank all members of the STOPSTORM.eu consortium (see https://stopstorm.eu/en/consortium) and especially the credentialing and audit committee. We kindly thank the European Union’s Horizon-2020 research and innovation programme for funding this project under grant agreement No. 945119

Effect of low-dose radiotherapy on the circulating levels of paraoxonase-1-related variables and markers of inflammation in patients with COVID-19 pneumonia

The aim of our study was to investigate the changes produced by low-dose radiotherapy (LDRT) in the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1) and inflammatory markers in patients with COVID-19 pneumonia treated with LDRT and their interactions with clinical and radiological changes. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 30 patients treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as PON1-related variables, cytokines, and radiological parameters were analyzed before LDRT, at 24 h, and 1 week after treatment. Twenty-five patients (83.3%) survived 1 week after LDRT. Respiratory function and radiological images improved in survivors. Twenty-four hours after LDRT, PON1 concentration significantly decreased, while transforming growth factor beta 1 (TGF-β1) increased with respect to baseline. One week after LDRT, patients had increased PON1 activities and lower PON1 and TGF-β1 concentrations compared with 24 h after LDRT, PON1 specific activity increased, lactate dehydrogenase (LDH), and C-reactive protein (CRP) decreased, and CD4+ and CD8+ cells increased after one week. Our results highlight the benefit of LDRT in patients with COVID-19 pneumonia and it might be mediated, at least in part, by an increase in serum PON1 activity at one week and an increase in TGF-β1 concentrations at 24 h

Tumor bed boost radiotherapy in the conservative treatment of breast cancer: a review of intra-operative techniques and outcomes

Conservative surgery is the preferred treatment in the management of breast cancer followed by adjuvant whole-breast irradiation. Since the tumor bed is the main site of relapse, boost doses are conveniently administered according to risk factors for local relapse to increase the efficacy of the treatment. The benefit of a radiation boost is well established and it can be performed by several techniques like brachytherapy, external radiation or intraoperative radiotherapy. Greater precision in localizing the tumor cavity, immediacy and increased biological response are the main advantages of intraoperative boost irradiation. This modality of treatment can be performed by means of mobile electron accelerators or low-photon X-ray devices. There is a lot of research and some published series analyzing the results of the use of an intraoperative boost as an adjuvant treatment, after neoadjuvant systemic therapy and in combination with some reconstructive surgeries. This review discusses advantages of intraoperative radiotherapy and presents the main results of a boost in terms of local control, survival, tolerance and cosmesis

Early mortality in bone marrow transplantation for acute lymphocytic leukaemia a multivariate analysis of risk factors

Objectives: bone marrow transplantation is still associated with a high case-fatality rate. This study was conducted to identify the risk factors for early mortality in acute lymphocytic leukaemia patients treated with bone marrow transplantation. Methods: prospectively collected data on 76 acute lymphocytic leukaemia patients, treated with 60 mg/kg cyclophosphamide for two consecutive days, before (32 patients) or after (44 patients) total body irradiation who received an allogeneic (56 patients) or autologous (20 patients) bone marrow transplantation were considered in the multivariate analysis including fifteen potentially prognostic variables for early mortality. Results: in the entire group, patients older than 20 years had a relative risk for early mortality of 3.96 (95% confidence interval (CI): 1.33-11.76) and those with a Karnofsky Index lower than 90% had a relative risk of 5.56 (95% CI: 1.29-25). In the subgroup of allogeneic patients, those over 20 years had a relative risk of 5.17 (95% CI: 1.30-20.6); the relative risk for patients with a Karnofsky index < 90% was 10.55 (95% CI: 1.55-71.43) and 8.04 (95% CI: 43-45.07) for acute severe graft-versus-host disease. Among radiation therapy variables only dose-rate showed a trend towards better prognosis in patients treated with less than 5 cGy/min. Conclusions: in our patients and within the range of treatment variables studied, age, Karnofsky index, and graft-versus-host disease are the most important factors related with early mortality

STereotactic Arrhythmia Radioablation (STAR): the standardized treatment and outcome platform for stereotactic therapy of re-entrant tachycardia by a multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe

Data de publicació electrònica: 07-04-2023The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 945119

DNA damage protection for enhanced bacterial survival under simulated low earth orbit environmental conditions in Escherichia coli

Some organisms have shown the ability to naturally survive in extreme environments, even outer space. Some of these have natural mechanisms to resist severe DNA damage from conditions such as ionizing and non-ionizing radiation, extreme temperatures, and low pressures or vacuum. A good example can be found in Deinococcus radiodurans, which was exposed to severe conditions such as those listed in the Exposure Facility of the International Space Station (ISS) for up to three years. Another example are tardigrades (Ramazzottius varieornatus) which are some of the most resilient animals known. In this study, the survival under simulated Low earth Orbit (LEO) environmental conditions was tested in Escherichia coli. The radiation resistance of this bacteria was enhanced using the Dsup gene from R. varieornatus, and two more genes from D. radiodurans involved in DNA damage repair, RecA and uvrD. The enhanced survival to wide ranges of temperatures and low pressures was then tested in the new strains. This research constitutes a first step in the creation of new bacterial strains engineered to survive severe conditions and adapting existing species for their survival in remote environments, including extra-terrestrial habitats. These strains could be key for the development of environments hospitable to life and could be of use for ecological restoration and space exploration. In addition, studying the efficacy and the functioning of the DNA repair mechanisms used in this study could be beneficial for medical and life sciences engineering

Early mortality in bone marrow transplantation for acute lymphocytic leukaemia a multivariate analysis of risk factors

Objectives: bone marrow transplantation is still associated with a high case-fatality rate. This study was conducted to identify the risk factors for early mortality in acute lymphocytic leukaemia patients treated with bone marrow transplantation. Methods: prospectively collected data on 76 acute lymphocytic leukaemia patients, treated with 60 mg/kg cyclophosphamide for two consecutive days, before (32 patients) or after (44 patients) total body irradiation who received an allogeneic (56 patients) or autologous (20 patients) bone marrow transplantation were considered in the multivariate analysis including fifteen potentially prognostic variables for early mortality. Results: in the entire group, patients older than 20 years had a relative risk for early mortality of 3.96 (95% confidence interval (CI): 1.33-11.76) and those with a Karnofsky Index lower than 90% had a relative risk of 5.56 (95% CI: 1.29-25). In the subgroup of allogeneic patients, those over 20 years had a relative risk of 5.17 (95% CI: 1.30-20.6); the relative risk for patients with a Karnofsky index < 90% was 10.55 (95% CI: 1.55-71.43) and 8.04 (95% CI: 43-45.07) for acute severe graft-versus-host disease. Among radiation therapy variables only dose-rate showed a trend towards better prognosis in patients treated with less than 5 cGy/min. Conclusions: in our patients and within the range of treatment variables studied, age, Karnofsky index, and graft-versus-host disease are the most important factors related with early mortality