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.

[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.

[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.

[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.

[Practical risk analysis]. / Analyse des risques a priori en pratique.

Risk analysis is typically considered from two complementary points of view: predictive analysis performed prior, and retrospective analysis, which follows the internal reporting of adverse situations or malfunctions, both on the organizational and material or human aspects. The purpose of these additional analyzes is to ensure that planned or implemented measures allow to keep risks to a level deemed tolerable or acceptable at a given time and in a given situation. Where a risk is deemed unacceptable, risk reduction measures should be considered (prevention, limiting the consequences and protection).

French multicentre clinical evaluation of helical TomoTherapy for anal cancer in a cohort of 64 consecutive patients.

PURPOSE/OBJECTIVES: To assess feasibility and toxicity of Helical TomoTherapy for treating anal cancer patients. METHODS: From 2007 to 2011, 64 patients were consecutively treated with TomoTherapy in three centres for locally advanced squamous-cell anal carcinoma (T2 > 4 cm or N positive). Prescribed doses were 45 Gy to the pelvis including inguinal nodes and 59.4 Gy to the primary site and involved nodes with fractions of 1.8 Gy, five days a week. A positional Megavoltage Computed Tomography was performed before each treatment session. All acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events version 3.0. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Median follow-up was 22.9 months. Fifty-four women and 10 men were treated (median age: 62 years). Nineteen patients (29.7%) had T2, 16 patients (25.0%) T3, and 27 patients (42.2%) T4 tumours. Thirty-nine patients (60.9%) had nodal involvement. Median tumour size was 45 mm (range, 10-110 mm). Seven patients had a colostomy before treatment initiation. Fifty-seven patients received concomitant chemotherapy (5-FU/cisplatin or 5-FU/mitomycin-based therapy). Forty-seven patients (73.4 %) experienced a complete response, 13 a partial response or local recurrence, and 11 had salvage surgery; among these, six became complete responders, three experienced metastatic failure, and two local failure. At least four patients experienced metastatic recurrence (concomitant to a local failure for one patient). The two-year overall survival was 85.6% (95 %CI [71.1%-93.0%]), and the one-year disease-free survival, and colostomy-free survival were 68.7% (95 %CI [54.4%-79.4]), and 75.5% (95 %CI [60.7%-85.3%]) respectively. Overall survival, disease-free survival and colostomy free-survival were significantly better for women than men (p = 0.002, p = 0.004, and p = 0.002 respectively). Acute grade ≥3 toxicity included dermatologic (46.9% of patients), gastrointestinal (20.3%), and hematologic (17.2%) toxicity. Acute grade 4 hematologic toxicity occurred in one patient. No grade 5 event was observed. CONCLUSIONS: TomoTherapy for locally advanced anal cancer is feasible. In our three centres of expertise, this technique appeared to produce few acute gastrointestinal toxicities. However, high rates of dermatologic toxicity were observed. The therapeutic efficacy was within the range of expectations and similar to previous studies in accordance with the high rates of locally advanced tumours and nodal involvement.

[Implementing new technology in radiation oncology: The French agency for nuclear safety (ASN) report]. / Conditions de mise en œuvre des « nouvelles techniques et pratiques ¼ en radiothérapie. Synthèse du rapport du groupe de travail issu du groupe permanent d'experts en radioprotection médicale de l'Autorité de sûreté nucléaire.

In August 2013, the French nuclear safety agency (ASN) requested the permanent group of experts in radiation protection in medicine (GPMED) to propose recommendations on the implementation of new technology and techniques in radiation oncology. These recommendations were finalized in February 2015 by the GPMED. In April 2015, the ASN sent a letter to the French ministry of health (DGS/DGOS), and its national health agencies (ANSM, INCa, HAS). In these letters, ASN proposed that, from the 12 recommendations made by the GPMED, an action plan should be established, whose control could be assigned to the French national cancer institute (INCa), as a pilot of the national committee for radiotherapy and that this proposal has to be considered at the next meeting of the national committee of radiotherapy.

[Irradiation in stereotactic conditions: prerequisites]. / Radiothérapie en conditions stéréotaxiques : les prérequis.

Indications of treatment by stereotactic body radiotherapy are dramatically increasing due to new potential indications. The conditions associated with the treatment delivery are multiple. The first step of the process is crucial. It is related to the validation of the indication proposed during the multidisciplinary meeting as regard the evidence-based proof of the concept. These emerging techniques mainly extracranial stereotactic body irradiation do not benefit from long-term evaluation in terms of efficiency as well as normal tissue late toxicities. Priority should be given to prospective independent clinical trials, validated by an independent scientific committee, performed under a relevant and well dedicated multicentric quality assurance program aiming to improve knowledge and selection of indications. The SFRO is still working with others professionals on the definition of the conditions for the implementation of such treatments and actively collaborates with the authorities to define the appropriate conditions to preserve the quality of the treatment delivery under these specific conditions.

[Nationwide implementation of stereotactic radiotherapy: the challenges of initial training and continuing professional education]. / Mise en œuvre de la radiothérapie stéréotaxique extracrânienne : enjeux de la formation initiale et continue.

Stereotactic body radiation therapy is a rapidly growing advanced treatment technique that delivers high radiation dose with great precision. The implementation of stereotactic body radiation therapy should be associated with a specific initial training and continuing professional education for radiation oncologists and medical physicists. The creation of a French stereotactic body radiation therapy group gathering radiation oncologists (SFRO and AFCOR) and medical physicists (SFPM) is mandatory in order to create dedicated national guidelines, prospective databases and to promote clinical trials in this field.

[Impact of dynamic IMRT and tomotherapy in pelvic cancers: a prospective dosimetric study with 51 patients]. / Apport de la RCMI rotationnelle et de la tomothérapie hélicoïdale dans les cancers pelviens : étude dosimétrique prospective sur 51 patients.

PURPOSE: To compare the dosimetric results of different techniques of dynamic intensity modulated radiation therapy (IMRT) in patients treated for a pelvic cancer with nodal irradiation. PATIENTS AND METHODS: Data of 51 patients included prospectively in the Artpelvis study were analyzed. Thirty-six patients were treated for a high-risk prostate cancer (13 with helical tomotherapy, and 23 with Rapid'Arc(®)) and 15 patients were treated for a localized anal cancer (nine with helical tomotherapy and six with Rapid'Arc(®)). Plan quality was assessed according to several different dosimetric indexes of coverage of planning target volume and sparing of organs at risk. RESULTS: Although some dosimetric differences were statistically significant, helical tomotherapy and Rapid'Arc provided very similar and highly conformal plans. Regarding organs at risk, Rapid'Arc(®) provided better pelvic bone sparing with a lower non-tumoral integral dose. CONCLUSION: In pelvis cancer with nodal irradiation, Rapid'Arc and helical tomotherapy provided very similar plans. The clinical evaluation of Artpelvis study will verify this equivalence hypothesis.