Radiation therapy of the primary tumour and/or metastases of digestive metastatic cancers.

Metastatic gastrointestinal cancer is not an uncommon situation, especially for pancreatic, gastric, and colorectal cancers. In this setting, few data are available on the impact of the treatment of the primary tumour. Oligometastatic disease is associated with longer survival in comparison with more advanced disease. Metastasis-directed therapy, such as stereotactic body radiotherapy, seems related to better outcomes, but the level of evidence is low. In most tumour locations, prospective data are very scarce and inclusion in ongoing trials is strongly recommended.

Stereotactic body radiation therapy for liver metastases in oligometastatic disease.

Oligometastatic cancers designate cancers in which the number of metastases is less than five, corresponding to a particular biological entity whose prognosis is situated between a localized and metastatic disease. The liver is one of the main sites of metastases. When patients are not suitable for surgery, stereotactic body radiotherapy provides high local control rate, although these data come mainly from retrospective studies, with no phase III study results. The need for a high therapeutic dose (biologically effective dose greater than 100Gy) while respecting the constraints on the organs at risk, and the management of respiratory movements require expertise and sufficient technical prerequisites. The emergence of new techniques such as MRI-guided radiotherapy could further increase the effectiveness of stereotactic radiotherapy of liver metastases, and thus improve the prognosis of these oligometastatic cancers.

Beyond hyperglycemia: glycaemic variability as a prognostic factor after acute ischemic stroke.

INTRODUCTION: Glycaemic variability (GV) refers to variations in blood glucose levels, and may affect stroke outcomes. This study aims to assess the effect of GV on acute ischaemic stroke progression. METHODS: We performed an exploratory analysis of the multicentre, prospective, observational GLIAS-II study. Capillary glucose levels were measured every 4 hours during the first 48 hours after stroke, and GV was defined as the standard deviation of the mean glucose values. The primary outcomes were mortality and death or dependency at 3 months. Secondary outcomes were in-hospital complications, stroke recurrence, and the impact of the route of insulin administration on GV. RESULTS: A total of 213 patients were included. Higher GV values were observed in patients who died (n = 16; 7.8%; 30.9 mg/dL vs 23.3 mg/dL; p = 0.05). In a logistic regression analysis adjusted for age and comorbidity, both GV (OR = 1.03; 95% CI, 1.003-1.06; p = 0.03) and stroke severity (OR = 1.12; 95% CI, 1.04-1.2; p = 0.004) were independently associated with mortality at 3 months. No association was found between GV and the other outcomes. Patients receiving subcutaneous insulin showed higher GV than those treated with intravenous insulin (38.95 mg/dL vs 21.34 mg/dL; p < 0.001). CONCLUSIONS: High GV values during the first 48 hours after ischaemic stroke were independently associated with mortality. Subcutaneous insulin may be associated with higher VG levels than intravenous administration.

Más allá de la hiperglucemia: la variabilidad glucémica como factor pronóstico en el infarto cerebral agudo / Beyond hyperglycemia: glycaemic variability as a prognostic factor after acute ischemic stroke

Introducción: La variabilidad glucémica (VG) hace referencia a las oscilaciones en los niveles de glucosa en sangre y podría influir en el pronóstico del ictus. Objetivo: Analizar el efecto de la VG en la evolución del infarto cerebral agudo (IC).MétodosAnálisis exploratorio del estudio GLIAS-II (multicéntrico, prospectivo y observacional). Se midieron los niveles de glucemia capilar cada cuatro horas durante las primeras 48 horas y la VG se definió como la desviación estándar de los valores medios. Variables principales: mortalidad y muerte o dependencia a los tres meses. Variables secundarias: porcentaje de complicaciones intrahospitalarias y de recurrencia de ictus, e influencia de la vía de administración de insulina sobre la VG.ResultadosSe incluyeron 213 pacientes. Los pacientes que fallecieron (N = 16;7,8%) presentaron mayores valores de VG (30,9 mg/dL vs. 23,3 mg/dL; p = 0,05). En el análisis de regresión logística ajustado por edad y comorbilidad, tanto la VG (OR = 1,03; IC del 95%: 1,003-1,06: p = 0,03) como la gravedad del IC (OR = 1,12; IC del 95%: 1,04-1,2; p = 0,004) se asociaron de forma independiente con la mortalidad a los tres meses. No se encontró asociación entre la VG y las demás variables de estudio. Los pacientes que recibieron tratamiento con insulina subcutánea mostraron una mayor VG que los tratados con insulina intravenosa (38,9 mg/dL vs. 21,3 mg/dL; p < 0,001).ConclusionesValores elevados de VG durante las primeras 48 horas tras el IC se asociaron de forma independiente con la mortalidad. La administración subcutánea de insulina podría condicionar una mayor VG que la vía intravenosa. (AU)

Introduction: Glycaemic variability (GV) refers to variations in blood glucose levels, and may affect stroke outcomes. This study aims to assess the effect of GV on acute ischaemic stroke progression.MethodsWe performed an exploratory analysis of the multicentre, prospective, observational GLIAS-II study. Capillary glucose levels were measured every 4 hours during the first 48 hours after stroke, and GV was defined as the standard deviation of the mean glucose values. The primary outcomes were mortality and death or dependency at 3 months. Secondary outcomes were in-hospital complications, stroke recurrence, and the impact of the route of insulin administration on GV.ResultsA total of 213 patients were included. Higher GV values were observed in patients who died (n = 16; 7.8%; 30.9 mg/dL vs 23.3 mg/dL; p = 0.05). In a logistic regression analysis adjusted for age and comorbidity, both GV (OR = 1.03; 95% CI, 1.003-1.06; p = 0.03) and stroke severity (OR = 1.12; 95% CI, 1.04-1.2; p = 0.004) were independently associated with mortality at 3 months. No association was found between GV and the other outcomes. Patients receiving subcutaneous insulin showed higher GV than those treated with intravenous insulin (38.95 mg/dL vs 21.34 mg/dL; p < 0.001).ConclusionsHigh GV values during the first 48 hours after ischaemic stroke were independently associated with mortality. Subcutaneous insulin may be associated with higher VG levels than intravenous administration. (AU)

[Quality assurance of radiotherapy in clinical research]. / Assurance qualité de la radiothérapie en recherche clinique.

Quality assurance for radiotherapy of a clinical trial is an important step from the design of the clinical trial. A precise definition of quality assurance must be given in detail in the clinical protocol of the clinical trial. By its implementation, quality assurance allows a homogeneity of the clinical trial, which can lead to a reduction of the biases of results interpretation for the clinical trial. The complexity of the radiotherapy to be carried out within the framework of the clinical trial can induce a gradation for the radiotherapy quality assurance program of the trial. However, the following steps are always present and must be described either directly in the clinical protocol or in a specific chapter, radiotherapy quality assurance, of the clinical protocol. The detailed characteristics of the medical imaging required to prepare for the treatment, the delineation of the targets and organs at risk, the requirements related to the planning, the treatment itself, possibly including the positioning repositioning control images, of the patient. For the delineation and planning stages, it is common to set up benchmarking based on test cases (dummy run, dry run). Their validation makes it possible for the center to get credentials for the clinical trial. Some trials can provide for an additional quality assurance point, such End-to-End test for which the investigating center must carry out, according to the clinical protocol, the preparation, the planning, the treatment on an anthropomorphic test object containing models of targets, organs at risk as well as dosimeters. Quality assurance of radiotherapy in clinical research is an essential part to be taken into account from the design of the clinical study. The commitment of the investigating center in terms of human and material resources in compliance with the protocol and in the quality assurance of the trial constitute a guarantee of limitation of the biases for the study and its interpretation, facilitating the answer of the scientific question asked by the trial.

Quality/risk management system in radiotherapy: Changes afoot.

The French sanitary and regulatory context in which radiotherapy centres are comprised is evolving. Risk and quality management systems are currently adapting to these evolutions. The French nuclear safety agency (ASN) decision of July 1st 2008 on quality assurance obligations in radiotherapy has reached 10 years of age, and the French high authority of health (HAS) certification system 20 years now. Mandatory tools needed for the improvement of quality and safety in healthcare are now well known. From now on, the focus of healthcare policies is oriented towards evaluation of efficiency of these new organisations designed following ASN and HAS nationwide guidelines.

Guidelines for external radiotherapy and brachytherapy procedures: 3rd edition.

The purpose of the first two editions of the guidelines for external radiotherapy procedures, published in 2007 and 2016 respectively, was to issue recommendations aimed at optimising, harmonising and standardising practices. The purpose of this third edition, which includes brachytherapy, is identical while also taking into account recent technological improvements (intensity modulation radiation therapy, stereotactic radiotherapy, and three-dimension brachytherapy) along with findings from literature. Part one describes the daily use of general principles (quality, security, image-guided radiation therapy); part two describes each treatment step for the main types of cancer.

Specificities of clinical research in radiotherapy.

The aim of this review is to present the specificities of clinical research in radiation oncology. Objectives are similar to all research in oncology: to improve the efficacy and to decrease toxic effects. Phase III trials remain the main methodology to demonstrate an improvement in efficiency, but phase I-II and registers are also important tools to validate an improvement in the therapeutic index with new technologies. In this article we discuss the special features of end-points, selection of population, and design for radiation oncology clinical trials. Quality control of delivered treatments is an important component of these protocols. Financial issues are also discussed, in the particular context of France.

External irradiation treatment process.

The purpose of this article is to describe the external irradiation process and updated recommendations of the French society for radiation oncology for patient follow-up.

Beyond hyperglycemia: glycaemic variability as a prognostic factor after acute ischemic stroke. / Más allá de la hiperglucemia: la variabilidad glucémica como factor pronóstico en el infarto cerebral agudo.

INTRODUCTION: Glycaemic variability (GV) refers to variations in blood glucose levels, and may affect stroke outcomes. This study aims to assess the effect of GV on acute ischaemic stroke progression. METHODS: We performed an exploratory analysis of the multicentre, prospective, observational GLIAS-II study. Capillary glucose levels were measured every 4 hours during the first 48 hours after stroke, and GV was defined as the standard deviation of the mean glucose values. The primary outcomes were mortality and death or dependency at 3 months. Secondary outcomes were in-hospital complications, stroke recurrence, and the impact of the route of insulin administration on GV. RESULTS: A total of 213 patients were included. Higher GV values were observed in patients who died (n = 16; 7.8%; 30.9 mg/dL vs 23.3 mg/dL; p = 0.05). In a logistic regression analysis adjusted for age and comorbidity, both GV (OR = 1.03; 95% CI, 1.003-1.06; p = 0.03) and stroke severity (OR = 1.12; 95% CI, 1.04-1.2; p = 0.004) were independently associated with mortality at 3 months. No association was found between GV and the other outcomes. Patients receiving subcutaneous insulin showed higher GV than those treated with intravenous insulin (38.95 mg/dL vs 21.34 mg/dL; p < 0.001). CONCLUSIONS: High GV values during the first 48 hours after ischaemic stroke were independently associated with mortality. Subcutaneous insulin may be associated with higher VG levels than intravenous administration.

[Overview of adaptive radiotherapy in 2019: From implementation to clinical use]. / État des lieux de la radiothérapie adaptative en 2019 : de la mise en place à l'utilisation clinique.

Intensity modulated radiotherapy combined with image guided radiotherapy has led to increase the precision of external beam radiotherapy. However, intra or inter-fraction anatomical variations are frequent during the treatment course and can cause under-dosing of the target volume and/or over-dosing of the organs at risk. Several adaptive radiotherapy (ART) strategies can be defined to compensate these anatomical variations. The purpose of this article is to provide an overview of available ART strategies: offline, online, hybrid (library of treatment plans) or in real-time, while considering the arrival of MR-Linac devices in radiotherapy departments. The tools required to these ART strategies such as auto-segmentation, deformable image registration, calculation of the daily dose or dose accumulation, are also described. Implementing an ART strategy requires a rigorous quality assurance process, at each stage and on the entire workflow, as well as prior organization and training from of all the trades. A strong multidisciplinary involvement is finally required in order to ensure ART treatments.

The effect of post-stroke hyperglycaemia on the levels of brain damage and repair-related circulating biomarkers: the Glycaemia in Acute Stroke Study II.

BACKGROUND AND PURPOSE: The aim was to identify whether post-stroke hyperglycaemia (PSH) influences the levels of circulating biomarkers of brain damage and repair, and to explore whether these biomarkers mediate the effect of PSH on the ischaemic stroke (IS) outcome. METHODS: This was a secondary analysis of the Glycaemia in Acute Stroke II study. Biomarkers of inflammation, prothrombotic activity, endothelial dysfunction, blood-brain barrier rupture, cell death and brain repair processes were analysed at 24-48 h (baseline) and 72-96 h (follow-up) after IS. The associations of the biomarkers and stroke outcome (modified Rankin Scale score at 3 months) based on the presence of PSH were compared. RESULTS: A total of 174 patients participated in this sub-study. Brain-derived neurotrophic factor (BDNF) at admission was negatively correlated with glucose levels. PSH was associated with a trend toward higher levels of endothelial progenitor cells (EPCs) at baseline. The EPCs in the PSH group then decreased in the follow-up samples (-8.5 ± 10.3) compared with the non-PSH group (4.7 ± 7.33; P = 0.024). However, neither BDNF nor EPC values had correlation with the 3-month outcome. Higher interleukin-6 at follow-up was associated with poor outcomes (modified Rankin Scale > 2) independently of PSH. CONCLUSION: Post-stroke hyperglycaemia appears to be associated with a negative regulation of BDNF and a different reaction in EPC levels. However, neither BDNF nor EPCs showed significant mediation of the PSH association with IS outcome, and only higher interleukin-6 in the follow-up samples (72-96 h) was related to poor outcomes, independently of PSH status. Further studies are needed to achieve definite conclusions.

[Reference bases of radiotherapy under stereotaxic conditions for bronchopulmonary, hepatic, prostatic, upper aero-digestive, cerebral and bone tumors or metastases]. / Bases référentielles de la radiothérapie en conditions stéréotaxiques pour les tumeurs ou métastases bronchopulmonaires, hépatiques, prostatiques, des voies aérodigestives supérieures, cérébrales et osseuses.

Since decades, stereotactic radiotherapy has spread out worldwide. Published results are very numerous. To clarify obviousness among all the publications, this recommendation review was written. Voluntarily, authors limited analysis of international best evidence literature on malignant tumors of lung, liver, prostate, head and neck, and metastasis of bone and brain. These data could be used to advance standardization and quality improvement of treatments performed in the nationwide radiotherapy departments and can provide useful guidance for centers worldwide.

[What does the medical physicist expect from the radiation oncologist and vice versa?] / Qu'attend le physicien médical de l'oncologue radiothérapeute et inversement ?

The cooperation between radiation oncologist and medical physicist is essential to guarantee the quality and safety of the irradiation of our patients. It would be wrong to consider that the intervention of medical physicists in the patient management process is limited to the provision of calibrated and controlled equipment and to guarantee the validity of the dose distribution and the treatment time, while the radiation oncologist has the complete control of all clinical activities related to irradiation. The intervention of physicists at the stage of acquisition of anatomical data and throughout the phase of optimization of the treatment is already a reality. The recognition of the profession of medical physicist as a health profession comes to legitimize this intervention. Should physician-physicist cooperation be limited to these common tasks and participation in continuing care? Can we envisage a true synergy of action that goes beyond the field of care? The answer to the question: what does the physicist expect from the radiation oncologist and vice versa may bring elements to reinforce tomorrow's cooperation. This article is the second part of the question.

Glycemia in Acute Stroke II study: a call to improve post-stroke hyperglycemia management in clinical practice.

BACKGROUND AND PURPOSE: The aim of the study was to analyze the effect of conventional glucose management, which aimed to maintain glucose levels <155 mg/dL (8.5 mmol/L), on glucose control and the outcomes of patients with acute ischaemic stroke (IS) in a clinical practice setting. METHODS: This was a multicenter, prospective cohort study of patients with acute IS. Patients were classified into four groups based on their initial 48-h capillary glucose levels and the administration of and response to corrective treatment: (i) untreated and maximum glucose levels <155 mg/dL (8.5 mmol/L) within the first 48 h; (ii) treated and good responders [glucose levels persistently <155 mg/dL (8.5 mmol/L)]; (iii) treated and non-responders [any glucose values ≥155 mg/dL (8.5 mmol/L) during the 24 h after the start of corrective treatment]; and (iv) untreated with any glucose value ≥155 mg/dL (8.5 mmol/L). The primary outcome was death or dependence at 3 months (blinded rater). RESULTS: A total of 213 patients were included. Ninety-seven (45.5%) patients developed glucose levels ≥155 mg/dL (8.5 mmol/L), 69 (71.1%) underwent corrective treatment and 31 patients underwent no corrective treatment at the physician's discretion [28 of whom had isolated values ≥155 mg/dL (8.5 mmol/L)]. Only 11 (16%) patients responded to conventional treatment, whereas 58 (84%) patients were non-responsive. Non-responders showed a twofold higher risk of death or dependence at 3 months (odds ratio, 2.472; 95% confidence interval, 1.096-5.576; P = 0.029). CONCLUSIONS: Lack of response to conventional treatment for glucose management in acute IS is frequent and associated with poor outcomes.

La socialización de los profesionales sanitarios y el papel de la resiliencia en el desarrollo de conductas de bienestar en el trabajo / Health personnel socialization and the role of resilience in the development of occupational well-being

Introducción. La socialización durante la formación de especialistas es una etapa clave en el posterior ajuste y bienestar laboral de los sanitarios en la organización hospitalaria. Objetivo. Analizar la relación de la socialización y la resiliencia con las respuestas de engagement en especialistas en formación. Método. Se llevó a cabo un muestreo de conveniencia, participando en el estudio 110 profesionales provenientes de 6 unidades docentes de diferentes hospitales. Se llevaron a cabo análisis descriptivos y mediacionales de las variables de estudio mediante SPSS 21 y Macro de Preacher y Hayes (2004). Resultados. Se muestran relaciones estadísticamente significativas entre socialización, resiliencia y engagement. También se muestra el papel mediador de la resiliencia (β=0,10; se=0,12; p<0,05; IC: [0,02-0,23]) para generar engagement en los profesionales sanitarios. Conclusiones. Se observa una interacción entre socialización y especialidad que modera la resiliencia. Así, se señalan cómo una socialización positiva y la resiliencia pueden promover un buen desempeño (AU)

Introduction. Socialization during the training of specialists is a key step in the subsequent adjustment and occupational well-being of health professionals in the hospital organisation. Objective. To analyse the relationship of socialization and resilience with the engagement responses of specialists in training. Method. Convenience sampling was used, with 110 professionals from six teaching units of different hospitals participating in the study. Descriptive and mediational analysis of the study variables were performed using SPSS 21 and Macro Preacher and Hayes (2004). Results. The results show statistically significant relationships between socialization, resilience, and engagement. The mediating role of resilience is also shown (β=0.10; se=0.12; p<0.05, 95% CI: [0.02-0.23]) to generate engagement in health professionals. Conclusions. An interaction effect is observed between socialization, and specialty moderates resilience. Therefore it can be seen that positive socialization and resilience can promote good performance (AU)

[Health personnel socialization and the role of resilience in the development of occupational well-being]. / La socialización de los profesionales sanitarios y el papel de la resiliencia en el desarrollo de conductas de bienestar en el trabajo.

INTRODUCTION: Socialization during the training of specialists is a key step in the subsequent adjustment and occupational well-being of health professionals in the hospital organisation. OBJECTIVE: To analyse the relationship of socialization and resilience with the engagement responses of specialists in training. METHOD: Convenience sampling was used, with 110 professionals from six teaching units of different hospitals participating in the study. Descriptive and mediational analysis of the study variables were performed using SPSS 21 and Macro Preacher and Hayes (2004). RESULTS: The results show statistically significant relationships between socialization, resilience, and engagement. The mediating role of resilience is also shown (ß=0.10; se=0.12; p<0.05, 95% CI: [0.02-0.23]) to generate engagement in health professionals. CONCLUSIONS: An interaction effect is observed between socialization, and specialty moderates resilience. Therefore it can be seen that positive socialization and resilience can promote good performance.

[The irradiation process]. / Processus du traitement par irradiation.

The purpose of this article is to describe the regulatory framework of the radiotherapy practice in France, the external irradiation and brachytherapy process and the guidelines for patient follow-up.

Validation of fast Monte Carlo dose calculation in small animal radiotherapy with EBT3 radiochromic films.

In preclinical studies, the absorbed dose calculation accuracy in small animals is fundamental to reliably investigate and understand observed biological effects. This work investigated the use of the split exponential track length estimator (seTLE), a new kerma based Monte Carlo dose calculation method for preclinical radiotherapy using a small animal precision micro irradiator, the X-RAD 225Cx. Monte Carlo modelling of the irradiator with GATE/GEANT4 was extensively evaluated by comparing measurements and simulations for half-value layer, percent depth dose, off-axis profiles and output factors in water and water-equivalent material for seven circular fields, from 20 mm down to 1 mm in diameter. Simulated and measured dose distributions in cylinders of water obtained for a 360° arc were also compared using dose, distance-to-agreement and gamma-index maps. Simulations and measurements agreed within 3% for all static beam configurations, with uncertainties estimated to 1% for the simulation and 3% for the measurements. Distance-to-agreement accuracy was better to 0.14 mm. For the arc irradiations, gamma-index maps of 2D dose distributions showed that the success rate was higher than 98%, except for the 0.1 cm collimator (92%). Using the seTLE method, MC simulations compute 3D dose distributions within minutes for realistic beam configurations with a clinically acceptable accuracy for beam diameter as small as 1 mm.