A step towards international prospective trials in carbon ion radiotherapy: investigation of factors influencing dose distribution in the facilities in operation based on a case of skull base chordoma

Background: Carbon ion radiotherapy (CIRT) has been delivered to more than 20,000 patients worldwide. International trials have been recommended in order to emphasize the actual benefits. The ULICE program (Union of Light Ion Centers in Europe) addressed the need for harmonization of CIRT practices. A comparative knowledge of the sources and magnitudes of uncertainties altering dose distribution and clinical effects during the whole CIRT procedure is required in that aim. Methods: As part of ULICE WP2 task group, we sent a centrally reviewed questionnaire exploring candidate sources of uncertainties in dose deposition to the ten CIRT facilities in operation by February 2017. We aimed to explore native beam characterization, immobilization, anatomic data acquisition, target volumes and organs at risks delineation, treatment planning, dose delivery, quality assurance prior and during treatment. The responders had to consider the clinical case of a clival chordoma eligible for postoperative CIRT according to their clinical practice. With the results, our task group discussed ways to harmonize CIRT practices. Results: We received 5 surveys from facilities that have treated 77% of the patients worldwide per November 2017. We pointed out the singularity of the facilities and beam delivery systems, a divergent definition of target volumes, the multiplicity of TPS and equieffective dose calculation approximations. Conclusion: Multiple uncertainties affect equieffective dose definition, deposition and calculation in CIRT. Although it is not possible to harmonize all the steps of the CIRT planning between the centers, our working group proposed counter-measures addressing the improvable limitations

2012 Activity Report of the Regional Research Programme on Hadrontherapy for the ETOILE Center

2012 is the penultimate year of financial support by the CPER 2007-2013 for ETOILE's research program, sustained by the PRRH at the University Claude Bernard. As with each edition we make the annual review of the research in this group, so active for over 12 years now. Over the difficulties in the decision-making process for the implementation of the ETOILE Center, towards which all our efforts are focussed, some "themes" (work packages) were strengthened, others have progressed, or have been dropped. This is the case of the eighth theme (technological developments), centered around the technology for rotative beam distribution heads (gantries) and, after being synchronized with the developments of ULICE's WP6, remained so by ceasing its activities, coinciding also with the retirement of its historic leader at IPNL, Marcel Bajard. Topic number 5 ("In silico simulations") has suffered the departure of its leader, Benjamin Ribba, although the work has still been provided by Branka Bernard, a former postdoctoral fellow in Lyon Sud, and now back home in Croatia, still in contract with UCBL for the ULICE project. Aside from these two issues (and the fact that the theme "Medico-economical simulations" is now directly linked to the first one ("Medical Project"), the rest of the teams are growing, as evidenced by the publication statistics at the beginning of this report. This is obviously due to the financial support of our always faithful regional institutions, but also to the synergy that the previous years, the European projects, the arrival of the PRIMES LabEx, and the national France Hadron infrastructure have managed to impulse. The Rhone-Alpes hadron team, which naturally includes the researchers of LPC at Clermont, should also see its influence result in a strong presence in France Hadron's regional node, which is being organized. The future of this regional research is not yet fully guaranteed, especially in the still uncertain context of ETOILE, but the tracks are beginning to emerge to allow past and present efforts translate into a long future that we all want to see established. Each of the researchers in PRRH is aware that 2013 will be (and already is) the year of great challenge : for ETOILE, for the PRRH, for hadron therapy in France, for French hadrontherapy in Europe (after the opening and beginning of treatments in the German [HIT Heidelberg, Marburg], Italian [CNAO, Pavia] and Austrian [MedAustron, Wien Neuerstadt]) centers. Let us meet again in early 2014 for a comprehensive review of the past and a perspective for the future ..

Radionecrosis after stereotactic radiotherapy for brain metastases

International audienceIntroduction: Radionecrosis (RN) represents the main complication of stereotactic radiotherapy (SRT) for brain metastases. It may be observed in up to 34% of cases at 24 months after treatment and associated with significant morbidity in 10-17%.Areas covered: Our aim is to discuss the results of original studies on RN related to SRT for brain metastases. Expert commentary: Although the development of RN is unpredictable, larger volume of the lesion, prior whole brain irradiation, and higher dose of radiation represent the major risk factors. RN appears on MRI as contrast-enhancing necrotic lesions, surrounded by edema, occurring at least 3 months after SRT, localized within fields of irradiation. No firm criteria are established. Surgery can provide symptomatic relief but is associated with a risk of complications. Corticosteroids are considered the standard of care treatment, despite limited efficacy and many adverse effects. Bevacizumab represents another interesting option that needs to be validated

Radiothérapie adaptative des cancers ORL : un outil permettant d’identifier les patients nécessitant une adaptation de leur traitement

International audiencePURPOSE:The purpose of this work was to implement a simple dosimetric alert tool in a retrospective study for six patients suffering from head and neck cancer to detect when a patient might require an adaptive radiotherapy.MATERIALS AND METHODS:The dosimetric tool generates a 3D cartography of two dosimetric complementary information: a dose variation tolerance map and a dose differential map. The tolerance map is calculated on the initial scanner (CTinit) using the planned dose distribution. It shows for each voxel of each delineated volume the availability for local dose variations during the course of radiotherapy without exceeding the dose threshold. The differential dose map is generated on the tomographic image CBCT (CBCTtreatment). It shows dose variations between the planned and the actual delivered dose distribution for each voxel. By comparing both maps, when a voxel presents a value superior to the corresponding dose variation tolerance, an alert is generated and the anatomical areas concerned are visually indicated to the physician.RESULTS:The application of the dosimetric tool on six patients with head and neck cancers reveals the ability of the tool to detect cases requiring a new treatment plan. Two patients whose the tumour shrinkage produced an increase of the delivered dose to the spinal cord beyond 45 Gy have been detected.CONCLUSION:The development of the dosimetric tool allows the automatic detection, with no delineation needs, of patients suffering from head and neck cancers requiring an adaptive strategy.Objectif de l’étudeL’objectif de ce travail était d’implémenter un outil d’alerte dosimétrique simple dans une étude rétrospective portant sur six patients ORL afin de détecter les situations où une adaptation de traitement était requise.Matériel et méthodesL’outil dosimétrique génère la cartographie tridimensionnelle de deux informations dosimétriques complémentaires : une carte de tolérance de variation de dose et une carte de différentielle de dose. La carte de tolérance est calculée à partir de la distribution de dose planifiée sur la scanographie initiale. Elle affiche pour chaque voxel de chaque organe délinéé, les variations acceptables de dose au cours des séances d’irradiation sans excéder les contraintes dosimétriques. La carte de différence de dose est générée suite au calcul de dose réelle sur l’image tomographique conique. Les variations de dose entre la distribution planifiée et la distribution réelle sont affichées pour chaque voxel. En comparant les deux cartes, lorsqu’un voxel présente une valeur supérieure à la tolérance de variation de dose correspondante, un système d’alerte se déclenche et la zone anatomique concernée est visuellement indiquée au médecin.RésultatsL’implémentation de l’outil d’alerte sur six patients atteints de cancer de la sphère ORL, avec une tomographie conique hebdomadaire, a révélé l’aptitude de l’outil à détecter les cas justifiant un nouveau plan de traitement. Deux patients chez qui la régression tumorale engendrait une majoration de la dose délivrée au canal médullaire au-delà de 45 Gy ont été détectés.ConclusionLe développement de cet outil de détection automatique permet d’orienter rapidement, et sans délinéation médicale, les patients atteints de cancer ORL vers une stratégie de radiothérapie adaptative

Cancer du canal anal : à l’ère de la radiothérapie conformationnelle avec modulation d’intensité, questions en suspens

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Radiothérapie conformationnelle des métastases osseuses vertébrales

International audienceAnalgesic external beam radiation therapy is a standard of care for patients with uncomplicated painful bone metastases and/or prevention of bone complications. In case of fracture risk, radiation therapy is performed after surgery in a consolidation of an analgesic purpose and stabilizing osteosynthesis. Radiotherapy is mandatory after vertebroplasty or kyphoplasty. Spinal cord compression - the only emergency in radiation therapy - is indicated postoperatively either exclusively for non surgical indication. Analgesic re-irradiation is possible in the case of insufficient response or recurrent pain after radiotherapy. Metabolic radiation, bisphosphonates or denosumab do not dissuade external radiation therapy for pain relief. Systemic oncological treatments can be suspended with a period of wash out given the risk of radiosensitization or recall phenomenon. Better yet, the intensity modulated radiotherapy and stereotactic radiotherapy can be part of a curative strategy for oligometastatic patients and suggest new treatment prospects

A single formula to describe radiation-induced protein relocalization Towards a mathematical definition of individual radiosensitivity

International audienceImmunofluorescence with antibodies against DNA damage repair and signaling protein is revolutionarising the estimation of the genotoxic risk. Indeed, a number of stress response proteins relocalize in nucleus as identifiable foci whose number, pattern and appearance/disappearance rate depend on several parameters such as the stress nature, dose, time and individual factor. Few authors proposed biomathematical tools to describe them in a unified formula that would be relevant for all the relocalizable proteins. Based on our two previous reports in this Journal (. Foray et al., 2005; Gastaldo et al., 2008), we considered that foci response to stress is composed of a recognition and a repair phase, both described by an inverse power function provided from a Euler's Gamma distribution. The resulting unified formula called "Bodgi's function" is able to describe appearance/disappearance kinetics of nuclear foci after any condition of genotoxic stress. By applying the Bodgi's formula to DNA damage repair data from 45 patients treated with radiotherapy, we deduced a classification of human radiosensitivity based on objective molecular criteria, notably like the number of unrepaired DNA double-strand breaks and the radiation-induced nucleo-shuttling of the ATM kinase. © 2013 Elsevier Ltd

ANOCEF Consensus Guideline on Target Volume Delineation for Meningiomas Radiotherapy

Purpose/Objective(s)Meningiomas are the most common primary intracranial tumor. They are developed at the expense of the dura, with an overall incidence which has increased over the past decade. To date, there is no published specific guideline about meningiomas target volume. No prospective study has defined a consensus for delineation in meningiomas’ radiotherapy. Therefore, target volume definition is mainly based on retrospective studies, with a heterogeneous population of patients. The aim of this paper is to describe delineation guidelines for meningiomas’ radiotherapy as an adjuvant or definitive treatment with Intensity Modulated Radiation Therapy (IMRT) and stereotactic radiation therapy (SRT) techniques.Materials/MethodsThis guideline is based on a consensus endorsed by a global multidisciplinary group of brain tumor experts’ member of the ANOCEF (French neuro-oncology association). A two round modified Delphi consensus was achieved, and the consensus was adopted by the RAND/UCLA method. The third round was carried out in videoconference, in order to allow experts to debate and argue on remaining uncertain proposals.ResultsTwenty experts from 17 radiotherapy center participated. After 3 rounds, all the proposals resulted in a consensus. The ANOCEF guideline committee proposed to perform an unenhanced planning CT scan, merged with a post-contrast MRI obtained at the time of radiotherapy and preoperative MRI in case of adjuvant treatment. GTV is defined by T1 contrast-enhancing lesion, thickened meninges, and directly invaded bone. For IMRT, the CTV include: Grade I: No margin around the GTV. Grade II: Margin of 5mm to expand GTV in normal brain tissue, hyperostosis, along the unthickened meninges and venous sinuses if the GTV is coming into contact. Grade III: Margin of 10mm to expand GTV in normal brain tissue, hyperostosis, along the unthickened meninges, and optic or cranial nerves in contact with GTV. In case of bone invasion, a margin of 5 or 10mm in the healthy bone around the GTV is recommended, for grade II or III respectively. Otherwise, it is considered as an anatomical barrier and does not need to be included in the target volume. In case of post-operative radiotherapy, no additional margin is required for CTV for grade I around tumor bed. A 5 and 10mm margin is required for grade II and III. The cranial flap should only be included in the CTV only over 5 or 10mm for grades II or III, in case of initially invaded bone. The drill holes and osteotomy areas should be included if they come into contact with target volume. SRT is not recommended for grades II and III, excluding relapse situation. CTV corresponds to GTV without additional margin.ConclusionThe current consensus provides a detailed delineation guideline for meningioma, suggesting smaller margins than the major studies published to date