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Résumé L’objectif de l’étude était de faire le point sur les résultats dans les principales indications de protonthérapie dans les cancers. Une revue systématique de la littérature a été réalisée par une sélection des études sur le site internet www.pubmed.com ( Medline ) à l’aide des mots-clés suivants : proton therapy , radiation therapy , cancer, chordoma , chondrosarcoma , uveal melanoma , retinoblastoma , meningioma , glioma , neurinoma , pituitary adenoma , medulloblastoma , ependymoma , craniopharyngioma et nasal cavity . Il existe de nombreuses études rétrospectives pour les indications classiques de protonthérapie qui sont les suivantes : tumeurs oculaires, des sinus, de la base du crâne et pédiatriques. Il n’existe toutefois aucune étude prospective, à part une de phase II dans le médulloblastome. L’utilisation de la protonthérapie dans ces indications est le fait d’un avantage dosimétrique qui prédit à doses égales avec la photonthérapie, une meilleure couverture tumorale et/ou un profil de toxicité plus favorable. En termes de contrôle tumoral, les protons sont historiquement au moins aussi efficaces que la photonthérapie, avec un profil de toxicité plus favorable prouvé pour les enfants (fonctions cognitives, fonction endocrinienne, cancers radioinduits) et un meilleur taux de contrôle tumoral pour les tumeurs des sinus du massif facial. Les avantages cliniques contrebalancent le coût de la technique dans les tumeurs pédiatriques en particulier. La protonthérapie pourrait, selon la situation, être proposée dans d’autres types de cancer. La protonthérapie a montré de bons résultats dans la prise en charge des tumeurs oculaires, des sinus de la face, des tumeurs pédiatriques, des tumeurs de la base du crâne et parachidiennes. Du fait des avantages dosimétriques de la technique, d’autres indications pourraient être posées à l’avenir. Purpose was to summarize results for proton therapy in cancer treatment. A systematic review has been done by selecting studies on the website www.pubmed.com ( Medline ) and using the following keywords: proton therapy, radiation therapy, cancer, chordoma, chondrosarcoma, uveal melanoma, retinoblastoma, meningioma, glioma, neurinoma, pituitary adenoma, medulloblastoma, ependymoma, craniopharyngioma and nasal cavity. There are several retrospective studies reporting results for proton therapy in cancer treatments in the following indications: ocular tumors, nasal tumors, skull-based tumors, pediatric tumors. There is no prospective study except one phase II trial in medulloblastoma. The use of proton therapy for these indications is due to dosimetric advantages offering better tumor coverage and organ at risk sparing in comparison with photon therapy. Clinical results are historically at least as efficient as photon therapy with a better toxicity profile in pediatric tumors (cognitive and endocrine functions, radiation-induced cancer) and a better tumoral control in tumors of the nasal cavity. Clinical advantages of proton therapy counterbalance its cost especially in pediatric tumors. Proton therapy could be used in other types of cancer. Proton therapy showed good outcome in ocular, nasal tumors, pediatric, skull-based and paraspinal tumors. Because of some dosimetric advantages, proton therapy could be proposed for other indications in cancer treatments. [ABSTRACT FROM AUTHOR]

Résumé Certaines tumeurs rares et de l’enfant sont de bonnes indications de protonthérapie, qui permet une forte probabilité de contrôle tumoral sans toxicité sévère ; la multiplication des centres de traitement s’est accompagnée d’une accumulation de données dosimétriques et cliniques pour d’autres cancers. L’objectif de cette étude est de faire une mise au point sur les indications potentielles de protonthérapie. Une recherche a été faite sur Medline avec les mots clés suivants : proton beam radiotherapy , cancer , heavy particle , charged particle . Aucun essai de phase III comparant la protonthérapie avec la meilleure photonthérapie n’a pour l’instant été publié, mais de nombreuses études rétrospectives ont montré des avantages dosimétriques et cliniques potentiels importants, laissant présager d’un avantage en termes de toxicité pour la protonthérapie, en particulier lorsque la contrainte de dose implique des organes en parallèle (tumeurs thoraciques et abdominales) ; de nombreux essais de phase 0, I, II, III et IV sont en cours pour déterminer la place de la protonthérapie dans les cancers les plus fréquents. L’utilisation de cette technique dans les cancers les plus fréquents est en expansion dans le cadre d’essais, mais certaines indications pourraient être envisagées devant des avantages dosimétriques majeurs in silico avec la protonthérapie. Proton beam therapy is indicated as a treatment for some rare tumours and paediatric tumours because the technique allows a good local control with minimal toxicity; the growing number of centres that use proton beam therapy is associated with an increase of dosimetric and clinical data for other malignant tumours as well. This paper reviews potential indications of proton beam therapy. A systematic review on Medline was performed with the following keywords proton beam therapy, cancer, heavy particle, charged particle. No phase III trial has been published using proton beam therapy in comparison with the best photon therapy, but numerous retrospective and dosimetric studies have revealed an advantage of proton beam therapy compared to photons, above all in tumours next to parallel organs at risk (thoracic and abdominal tumours). This could be accompanied with a better safety profile and/or a better tumoural control; numerous phase 0, I, II, III and IV studies are ongoing to examine these hypotheses in more common cancers. Use of proton beam therapy is growing for common cancers within clinical trials but some indications could be applied sooner since in silico analysis showed major advantages with this technique. [ABSTRACT FROM AUTHOR]

Systemic metastases from ovarian carcinoma are frequent, but they seldom affect the central nervous system. We present here the case of a patient treated for an ovarian cancer by surgery and chemotherapy. Three months after the end of chemotherapy, the patient developed cerebral metastases from ovarian carcinoma (CMOC) treated by iterative surgery and and whole brain irradiation. As the frequency of solitary cerebral metastasis of ovarian cancer is higher than with other cancers, it is likely that they behave slightly differently. Literature analysis reveals an increase in the incidence of CMOC since the middle of the nineties. CMOC can occur during or after adjuvant chemotherapy and the best management strategies to better define determinants of survival for patients are not well known. It appears that a better outcome of CMOC may be obtained by an aggressive treatment, if possible, including surgery, radiotherapy, and chemotherapy. Taking into account the increase in the incidence of the CMOC and their early occurrence, some authors have proposed a prophylactic brain radiotherapy in patients who receive adjuvant chemotherapy. [Copyright &y& Elsevier]

Preclinical and clinical data suggest a potential benefit in the addition of radiotherapy (RT) to immune-checkpoint inhibitors (ICI) during the treatment of advanced cancers. Nevertheless, the ideal patients for this approach and the optimal RT regimen is still debated. The aim of this study was to determine the effect RT schedule has on survival for advanced non-small cell lung cancer and melanoma patients (pts) treated with ICI (anti-PD1 or anti-CTLA4) and concomitant RT. A total of 58 pts were identified, of which 26 received RT concomitantly with ICI while the remaining 32 pts were treated with RT at the time of progression under ICI. The RT parameters associated with outcome include dose per fraction, biological effective dose, RT to all targets and lung irradiation. Independent predictors of improved progression-free survival were lung irradiation, melanoma histology, oligometastatic status (< 6 metastasis), presence of liver metastasis, PNN < 7000/mm3 and normal LDH. Independent predictors of improved overall survival were melanoma histology and normal LDH. Among pts who were irradiated at progression, 68.7% had an overall clinical benefit and had a median extension of ICI use by 2.3 months (range: 0-29.1), among which 2 presented with an abscopal effect. The irradiation of lung metastases may increase survival in patients under ICI. RT at progression could prolong the use of ICI, and neutrophilia and LDH should be considered during patient selection of this combined RT/ICI approach. [ABSTRACT FROM AUTHOR]

Il existe plus de 100 centres de proton thérapie dans le monde, et trois en France. La protonthérapie française est en phase de structuration et de montée en charge, avec l'ouverture récente des centres de Nice (2016) et Caen (2018) en plus du centre d'Orsay (2010) pour les indications corps entier. La prise en charge des enfants et adolescents-jeunes adultes est une priorité nationale partagée par les trois centres. L'action des trois centres français est coordonnée en termes d'adressage via le portail Protonshare sous l'égide de la Société Française de radiothérapie oncologique (SFRO). Les trois centres ont aussi une dynamique coordonnée d'offre de soin à des patients étrangers dans le cadre du réseau French Health Care du ministère des Affaires étrangères. Ils sont inscrits dans une démarche nationale et internationale (en particulier, en Europe, via l'European Proton Therapy Network) de participation à des essais thérapeutiques et des bases de données. Des actions concertées sont désormais favorisées en recherche préclinique via le réseau Radiotransnet. Dans ses développements, la protonthérapie française est bien représentée dans les congrès internationaux d'hadronthérapie. L'enseignement de la protonthérapie en France est proposé à plusieurs niveaux et ouvert aux centres photons, potentiellement adresseurs. La participation de l'ensemble des acteurs de la radiothérapie française est ainsi encouragée pour favoriser la participation de tous à la construction du niveau de preuve médicoscientifique requis pour une éventuelle extension future du parc de protonthérapie français. Among over 100 proton therapy centres worldwide in operation or under construction, French proton therapy is coming to full maturity with the recent opening of the Nice (1991, upgrade in 2016) and Caen (2018) facilities next to the Orsay (1991, upgrade in 2010) centre. Proton therapy is a national priority for children and young adults in all three centres. The patient-related activity of the three French centres is coordinated via the Protonshare portal to optimise referral by type of indication and available expertise in coordination with the French society of radiation oncology SFRO and French radiotherapy centres. The centres are recognised by the French Health Care excellence initiative, promoted by the ministry of Foreign Affairs. The three centres collaborate structurally in terms of clinical research and are engaged at the international level in the participation to European databases and research initiatives. Concerted actions are now also promoted in preclinical research via the Radiotransnet network. Ongoing French developments in proton therapy are well presented in international hadron therapy meetings, including European Proton Therapy Network and Particle Therapy Cooperative Oncology Group. Proton therapy teaching in France is offered at several levels and is open to colleagues from all radiation oncology centres, so that they are fully informed, involved and trained to facility recognition of possible indications and thereby to contribute to appropriate patient referral. This close collaboration between all actors in French radiation oncology facilitates the work to demonstrate the required level of medical and scientific evidence for current and emerging indications for particle therapy. Based on that, the future might entail a possible creation of more proton therapy facilities in France. [ABSTRACT FROM AUTHOR]

Résumé Objectif de l’étude La radiothérapie est en pédiatrie une indication rare, avec 800 à 900 enfants pris en charge par an en France. Les cancers de l’enfant représentent environ 1 % des cancers en France et pour la moitié, surviennent avant l’âge de 5 ans. La radiothérapie pédiatrique nécessite des moyens adaptés, des locaux, du temps et une formation spécifique. En France, en 2015, 18 centres sont accrédités par l’Institut national du cancer (INCa) pour cette activité. Matériel et méthodes Enquête menée en février 2015 sur la prise en charge des enfants (de 0 à 18 ans) dans les services de radiothérapie en France. L’enquête a été adressée aux oncologues radiothérapeutes concernés des 17 centres. Les questions concernaient l’aspect qualitatif et quantitatif, les aspects médicaux et organisationnels, ainsi que la place des manipulateurs dans la gestion de cette activité. Résultats Dix-sept centres ont répondu. En 2014, 889 enfants de moins de 18 ans ont été pris en charge Les services de radiothérapie sont en lien avec un à quatre services d’oncologie pédiatrique. Pour ce qui concerne l’accès aux anesthésies générales, trois centres effectuent un à sept traitement(s) sous anesthésie par an, trois centres de huit à dix, trois de dix à 24 et neuf centres sur 17 pratiquent des techniques d’hypnose. Sur le plan des ressources humaines, en 2015, 29 oncologues radiothérapeutes avaient une activité de radiothérapie pédiatrique. La place de manipulateurs investis est croissante et des formations spécifiques sont souhaitées. Concernant la préparation du traitement et le traitement, 13 centres ont des contentions spécifiques pédiatriques, 14 centres sur 16 ont recours à la radiothérapie avec modulation d’intensité si la dosimétrie est plus satisfaisante, dont 11 régulièrement pour les irradiations craniospinales. La radiothérapie des zones mobiles avec asservissement respiratoire ou en hypofractionnement est peu développée. Conclusion La radiothérapie pédiatrique est une activité spécifique nécessitant une gestion dédiée, tant au plan humain qu’organisationnel et médicoscientifique. Purpose Radiotherapy is a rare indication in paediatric oncology, with 800 to 900 children in treatment per year in France. Child cancers represent approximately 1% of cancers in France and half occur before the age of 5 years. Paediatric radiation requires appropriate tools, local, time and specific training. In France, in 2015, 18 centres are accredited by the French National Cancer Institute (INCa) for this activity. Material and methods Survey conducted in February 2015 on the care of children (0 to 18 years) in radiotherapy departments in France. The survey was sent to the radiation oncologists involved in the 18 centres. The questions concerned the qualitative and quantitative aspect, medical and organizational aspects, and the involvement of assistant practitioners in the management of this activity. Results Seventeen centres responded. In 2014, 889 children under 18 were treated in radiotherapy departments. These departments are working together with one to four paediatric oncology departments. Regarding access to general anaesthesia: three centres perform one to seven treatment(s) under anaesthesia per year, three centres eight to ten treatments under anaesthesia per year, three centres ten to 24 treatments under anaesthesia per year and nine centres out of 17 use hypnosis techniques. In terms of human resources, in 2015, 29 radiation therapists have a paediatric radiotherapy activity. Involvement of assistant practitioners is growing and specific training are desired. Regarding treatment preparation and delivery, 13 centres have specific paediatric contentions, 14 of 16 centres employ radiation intensity modulated if dosimetry is more satisfying with 11 regularly to the craniospinal irradiation. Radiotherapy on moving areas with respiratory gating or hypofractionation is under developed. Conclusion Paediatric radiation therapy is a specific activity requiring a dedicated management, both in human, organizational, medical and scientific aspects. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Stereotactic radiotherapy using the CyberKnife® has become a key treatment in the multidisciplinary management of secondary tumours, as well as primary benign or malignant tumours located within or adjacent to vertebral bodies and the spinal cord. The aim of this treatment is to improve local control and clinical response, including previously irradiated cases. Patients and methods: In this study, we present the first patients treated with CyberKnife® between December 2006 and December 2007 for spinal or paraspinal tumours. The primary aim was to assess the feasibility and tolerance of stereotactic radiotherapy using the CyberKnife®. Secondary aims were to establish the short-term local control, to calculate the local progression-free survival and overall survival. Clinical examination and imaging procedures were performed every three months. Response was assessed according to RECIST criteria. Results: During that period, 16 patients were treated with CyberKnife®. Thirteen patients had been pre-treated, three of whom had received spinal cord doses considered to be maximal. Three patients did not receive previous irradiation. The median age was 59 (36–74). The most frequent symptoms were pain (n = 8) and motor weakness (n = 4). The median dose was 30 Gy (16–50). The median number of fractions was 3 (1–5). No patient developed acute myelitis. Three patients developed acute reaction. Overall survival at 18 months was 72.4%, with a mean survival of 18.2 months (95% CI: 15.4–20.9). Local progression-free survival at 18 months was 58.4%, with a mean value of 16.9 months (95% CI: 13.6–20.2). Conclusion: The use of stereotactic radiotherapy with CyberKnife® represents a major progress in the management of paraspinal tumours. The main advantages are better sparing of the spinal cord and the possibility of increasing the dose to the tumour target volume. [Copyright &y& Elsevier]