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Intracranial radiotherapy has been improved, primarily because of the development of stereotactic approaches. While intracranial stereotactic body radiotherapy is mainly indicated for treatment of benign or malignant tumors, this procedure is also effective in the management of other neurological pathologies; it is delivered using GammaKnife® and linear accelerators. Thus, brain arteriovenous malformations in patients who are likely to experience permanent neurological sequelae can be managed by single session intracranial stereotactic body radiotherapy, or radiosurgery, in specific situations, with an advantageous benefit/risk ratio. Radiosurgery can be recommended for patients with disabling symptoms, which are poorly controlled by medication, such as trigeminal neuralgia, and tremors, whether they are essential or secondary to Parkinson's disease. This literature review aims at defining the place of intracranial stereotactic body radiotherapy in the management of patients suffering from non-tumoral refractory neurological pathologies. It is clear that the multidisciplinary collaboration of experienced teams from Neurosurgery, Neurology, Neuroradiology, Radiation Oncology and Medical Physics is needed for the procedures using high precision radiotherapy techniques, which deliver high doses to locations near functional brain areas. [ABSTRACT FROM AUTHOR]

Purpose. Glioblastoma (GBM) treatment still remains a complex challenge. Among alternatives or adjuvant therapies, photodynamic therapy (5-ALA PDT) appears to be a promising approach. 5-ALA PDT can be delivered intraoperatively, early after tumor resection, or interstitially according to brain tumor location. A treatment planning system was designed to manage dosimetry issues before PDT delivery. Methods. The TPS was developed according to a specific workflow from stereotactic image registration to light fluence rate modeling. Here, we describe a proof of concept of a treatment planning system (TPS) dedicated to interstitial 5-ALA PDT. This tool enables the planning of a whole treatment in surgical stereotactic conditions. Stereotactic registration and dosimetry components are detailed and evaluated. The registration process is compared to a commercial solution (Leksell Gamma Plan ® , Elekta ® , Sweden) defined as the ground truth and dosimetry model implemented in our TPS and is compared to numerical simulations. Results. Registration achieved a sub-millimetric mean relative error that matched the standard MRI resolution. Dosimetry comparison showed a negligible error between analytical and numerical models and enabled a validation of the dosimetry algorithm implemented. Conclusions. A treatment planning system was designed to achieve 5-ALA PDT simulations before the patients underwent surgery. Similarly, for radiation therapy, we proposed a system to plan and evaluate the 5-ALA PDT dosimetry for optimizing treatment delivery. Although this system remains to be perfected, this preliminary work aimed to demonstrate the feasibility of planning 5-ALA PDT treatments in stereotactic conditions. Future improvements will mainly focus on the optimization of the treatment delivery, automatic segmentation and GPU-accelerated Monte-Carlo management to take into account GBM tissue heterogeneity. [ABSTRACT FROM AUTHOR]

Because of high heterogeneity and invasiveness, treatment of GlioBlastoma Multiform (GBM) still remains a complex challenge. Several recent advanced therapies have improved precision of treatment deliverance. Multimodality imaging plays an increasingly important role in this process and images segmentation has become an essential part of the pipeline of standard treatment planning system. With the sophistication of multimodality information, the development of reliable and robust segmentation algorithms to overcome manual segmentation and optimize targeted treatment is highly expected. In this paper, we first introduce targeted therapies applied in the GBM clinical care, from routine or research. Different segmentation methods from state of the art are highlighted to achieve GBM delineation. New trends in GBM segmentation such as machine learning and multimodal features are discussed. These additional frameworks may achieve segmentation with refining capacities, active tumour probability mapping and, even, tumour relapse prediction capacities. [ABSTRACT FROM AUTHOR]

Résumé La radiothérapie en conditions stéréotaxiques des métastases cérébrales fait l’objet de débats entre experts et d’indications croissantes au sein des réunions de concertation polydisciplinaires. La définition des techniques de radiothérapie en conditions stéréotaxiques et ses modalités de prescription, ses indications et la balance efficacité contre toxicité sont à discuter. La radiothérapie en conditions stéréotaxiques est une technique d’irradiation dont la précision doit être de l’ordre du millimètre, utilisant différents types de matériels (cadre invasif ou non, photons X ou gamma), permettant de délivrer de fortes doses par séance (de 4 à 25 Gy) en un nombre limité de séances (d’une à cinq habituellement, pouvant aller jusqu’à sept à dix) avec un fort gradient de dose. Le mode de prescription de la dose dépend des matériels utilisés, les contraintes à respecter aux organes à risque variant selon les fractionnements choisis. La radiothérapie en conditions stéréotaxiques peut être proposée : (1) en combinaison avec une irradiation encéphalique totale dans le but d’améliorer la probabilité de survie d’un patient en bon état général, atteint d’une à trois métastases cérébrales, avec maladie extracrânienne contrôlée ; (2) pour ré-évolution d’une métastase cérébrale après irradiation encéphalique totale ; (3) après exérèse « complète » d’une métastase cérébrale volumineuse et/ou symptomatique ; (4) après découverte de trois à cinq métastases cérébrales nouvelles ou progressant malgré les traitements systémiques, peu ou pas symptomatiques. Il s’agit alors de différer l’irradiation encéphalique totale pour éviter sa neurotoxicité potentielle dans un but de contrôle purement focal, un strict suivi clinique et IRM tous les 3 mois permettant de réitérer les radiothérapies en conditions stéréotaxiques sans compromettre la survie. Toute concomitance de radiothérapie en conditions stéréotaxiques et de médicament ciblée doit être soigneusement discutée. Stereotactic radiotherapy of brain metastases is increasingly proposed after polydisciplinary debates among experts. Its definition and modalities of prescription, indications and clinical interest regarding the balance between efficacy versus toxicity need to be discussed. Stereotactic radiotherapy is a ‘high precision’ irradiation technique (within 1 mm), using different machines (with invasive contention or frameless, photons X or gamma) delivering high doses (4 to 25 Gy) in a limited number of fractions (usually 1 to 5, ten maximum) with a high dose gradient. Dose prescription will depend on materials, dose constraints to organs at risk varying with fractionation. Stereotactic radiotherapy may be proposed: (1) in combination with whole brain radiotherapy with the goal of increasing (modestly) overall survival of patients with a good performance status, 1 to 3 brain metastases and a controlled extracranial disease; (2) for recurrence of 1–3 brain metastases after whole brain radiotherapy; (3) after complete resection of a large and/or symptomatic brain metastases; (4) after diagnosis of 3–5 asymptomatic new or progressing brain metastases during systemic therapy, with the aim of delaying whole brain radiotherapy (avoiding its potential neurotoxicity) and maintaining a high focal control rate. Only a strict follow-up with clinical and MRI every 3 months will permit to deliver iterative stereotactic radiotherapies without jeopardizing survival. Simultaneous delivering of stereotactic radiotherapy with targeted medicines should be carefully discussed. [ABSTRACT FROM AUTHOR]

Résumé La chirurgie d’exérèse des métastases cérébrales a été bien évaluée pour les métastases uniques. Deux études randomisées de phase III ont montré que, lorsqu’elle est associée à une irradiation pancérébrale adjuvante, elle améliore significativement la probabilité de survie globale des patients. Cependant, même en présence de localisations cérébrales secondaires multiples, la chirurgie peut être indiquée. Pour des lésions accessibles à la radiochirurgie, la chirurgie d’exérèse sera privilégiée pour des lésions volumineuses, kystiques ou nécrotiques, très œdémateuses, situées en zones éloquentes ou de localisation cortico–sous-corticale. En outre, la chirurgie peut avoir un rôle diagnostique, en absence de documentation histologique de la maladie primitive, pour éliminer un diagnostic différentiel (abcès cérébral, lymphome, tumeur primitive, radionécrose, etc.). Enfin, la question de la documentation biologique de la maladie cérébrale peut se poser dans des situations particulières où une thérapie ciblée peut être proposée. La sélection des patients pour la chirurgie doit prendre en compte trois facteurs, le statut clinique et fonctionnel du patient, le statut de la maladie systémique et les caractéristiques des métastases intracrâniennes. Compte tenu de l’amélioration de la survie des patients liée en partie à l’émergence de thérapies ciblées efficaces, un regain d’intérêt a été apporté aux thérapeutiques locales dans les métastases cérébrales. La chirurgie d’exérèse représente à ce jour un outil majeur dans l’arsenal thérapeutique des métastases cérébrales, mais est également devenu un outil diagnostique et décisionnel à part entière pouvant influer sur la stratégie de prise en charge de ces patients. Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We studied the time course and location of post-movement beta synchronization (PMBS) in patients presenting with sensory deafferentation, in order to assess the hypothetical relationship between the PMBS and the cortical processing of movement-related somatosensory afferent inputs. Methods: We used the event-related synchronization (ERS) method. EEG activity was recorded (via a 128-electrode system) during brisk, unilateral right and left index finger extension by 10 patients presenting with neuropathic pain related to sensory deafferentation. Intra- and post-movement changes in beta source power were calculated relative to pre-movement baseline activity. We compared the PMBS results for the painful and non-painful body sides. Furthermore, PMBS patterns in patients were compared with those in nine healthy volunteers. Results: PMBS pattern related to the painful side had a spatial distribution, with an ipsilateral preponderance, significantly more restricted than PMBS pattern on the non-painful side and in the control group. There were no significant differences between patient PMBS patterns on the non-painful side and those in the control group. Conclusions: Sensory deafferentation disrupts normal PMBS patterns. Significance: This work provides additional arguments to the hypothesis supporting that the PMBS is influenced by movement-related somatosensory input processing. [Copyright &y& Elsevier]

Abstract: Objective: Abnormal low- and high-frequency oscillatory activities have been linked to abnormal movement control in Parkinson’s disease. We aimed to study how low- and high-frequency oscillatory activities are modulated by movement in the contralateral and ipsilateral subcorticocortical loops. Methods: We studied mu, beta and gamma rhythm event-related desynchronisation (ERD) and synchronisation (ERS) recorded from electrode contacts in the subthalamic nucleus (STN) areas and over the primary sensorimotor (PSM) cortex. Results: Mu and beta ERD/ERS patterns were very similar when comparing PSM cortex and STN areas and very different when comparing contralateral and ipsilateral structures. Beta rhythm ERS was more predominant over contralateral structures than over ipsilateral ones. Gamma rhythm ERS was only recorded from the contralateral STN area (particularly following administration of L-Dopa). For all patients, the best bipolar derivations – as defined by the earliest mu and beta ERD and the strongest beta and gamma ERS – always included the STN electrode contacts that produced the best clinical results. Conclusions: Movement-related activity is involved in the movement preparation in the contralateral subthalamo-cortical loop and in the movement execution in the bilateral subthalamo-cortical loops. Significance: Contralateral beta rhythm ERD seemed to be related to bradykinesia of the limb performing the movement. [Copyright &y& Elsevier]

Cerebral stereotaxy is an old methodology allowing an accurate approach of a lesion or a function, in constant renewal with the introduction of computers and robotic. There is a natural complementarity with recent neuroradiological investigations and together, it is possible to reach cerebral deep-seated or functional structures with inocuity and fiability for diagnosis and/or therapy. Its application is very large and also influences neuronavigation procedures, current in conventional neurosurgery. Tumoral stereotaxy is commonly used and achieves a better adaptation of the therapeutical strategy according to the lesions’ site and histological diagnosis. The development of functional stereotaxy is associated with the interest of the neurosurgical treatment of involuntary abnormal movements, without forgetting different aspects of surgery of chronic pain and intractable epilepsies. Moreover, the stereotactic methodology leads the concept of radiosurgery, which is in some indications a true alternative to open surgery (arteriovenous malformations, vestibular schwannoma, metastasis) under the control of accurate selection in a multidisciplinary approach. [Copyright &y& Elsevier]

Résumé La prise en charge des métastases cérébrales a évolué ces quinze dernières années et peut faire appel à des stratégies variables incluant des traitements plus ou moins agressifs, parfois combinés, permettant un allongement de la survie et une amélioration de la qualité de vie des patients. La décision thérapeutique est soumise à une réflexion pluridisciplinaire, prenant en compte des facteurs pronostiques établis incluant l’état général des patients, le statut de la maladie extracérébrale, le tableau clinique et radiologique des métastases cérébrales. Nous proposons, dans cet article, une stratégie de prise en charge basée sur l’état des connaissances et des ressources thérapeutiques actuelles. Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources. [ABSTRACT FROM AUTHOR]

Résumé L’incidence des métastases cérébrales est en augmentation en raison notamment de nouveaux agents thérapeutiques qui permettent une amélioration de la survie des patients, mais qui possèdent généralement une mauvaise diffusion à travers les barrières du système nerveux central. Les possibilités de prise en charge ont également évolué avec une meilleure connaissance des données immuno-histochimiques et de biologie moléculaire, l’apparition de nouvelles techniques chirurgicales, de radiothérapie, ainsi que les progrès réalisés avec les traitements systémiques. Le pronostic reste encore souvent limité à quelques mois, néanmoins une survie relativement longue peut désormais être observée dans quelques groupes de patients. Les facteurs pronostiques principaux concernent le type et le sous-type du cancer primitif, l’âge et l’état général du patient, le nombre et la localisation des métastases cérébrales, l’évolution de la maladie extracérébrale. La discussion multidisciplinaire doit tenir compte de l’ensemble de ces paramètres. Il faut également souligner que certains traitements, y compris la chirurgie et la radiothérapie, peuvent être proposés à visée symptomatique dans les phases palliatives de la maladie, justifiant de poursuivre la collaboration multidisciplinaire même dans les phases avancées de la maladie. Ce chapitre rapporte les recommandations proposées par le groupe de travail de l’Association de neuro-oncologie d’expression française (Anocef), l’ensemble des rédacteurs et relecteurs du référentiel. La prise en charge des métastases de cancers du sein et de cancers du poumon est discutée dans un chapitre dédié à ces deux entités tumorales, la prise en charge des métastases de mélanome est discutée dans un chapitre spécifique en raison principalement de la sensibilité différente à la radiothérapie cérébrale. The incidence of brain metastases is increasing because of the use of new therapeutic agents, which allow an improvement of overall survival, but with only a poor penetration into the central nervous system brain barriers. The management of brain metastases has changed due to a better knowledge of immunohistochemical data and molecular biological data, the development of new surgical, radiotherapeutic approaches and improvement of systemic treatments. Most of the time, the prognosis is still limited to several months, nevertheless, prolonged survival may be now observed in some sub-groups of patients. The main prognostic factors include the type and subtype of the primitive, age, general status of the patient, number and location of brain metastases, extracerebral disease. The multidisciplinary discussion should take into account all of these parameters. We should notice also that treatments including surgery or radiotherapy may be proposed in a symptomatic goal in advanced phases of the disease underlying the multidisciplinary approach until late in the evolution of the disease. This article reports on the ANOCEF (French neuro-oncology association) guidelines. The management of brain metastases of breast cancers and lung cancers are discussed in the same chapter, while the management of melanoma brain metastases is reported in a separate chapter due to different responses to the brain radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: In the context of chronic pain, the technics of neuromodulation have a significative place especially when they are neuropathic with a precise selection of the indications according to the neurophysiological, anatomical and clinical data. The choice is essentially based upon the severity and the site of pain. They are totally conservative, adaptable and reversible but it is necessary to organize a very rigorous clinical and technical follow-up according to a multidisciplinary approach. [Copyright &y& Elsevier]

The evaluation of response for brain metastases (BM) may be challenging in the context of treatment by stereotactic radiotherapy (SRT) or immunotherapy or both, which represent major therapeutic options for melanoma BM. We reviewed clinical and neuroimaging data of 62 melanoma patients with newly diagnosed BM treated by the combination of immunotherapy and SRT (n = 33, group A), immunotherapy alone (n = 10, group B) or SRT alone or in combination with other systemic therapies (BRAF inhibitors, n = 7; alkylating agents, n = 6; no systemic treatment, n = 6), (n = 19, group C). Response was assessed using RECIST 1.1, RANO or iRANO criteria. BRAF mutations were noted in 26 patients. Until BM diagnosis, a median of 1 (range 1-4) line of systemic treatment was given. At BM diagnosis, median age was 58 years (range 23-85.5). Fifty-four patients (87%) had 1-3 metastases. The median maximum diameter was 18.5 mm (range, 9-49). The median DS-GPA was 3 (1-4). After a median follow-up of 30.5 months for surviving patients, 39 patients have experienced CNS progression, 16 (48.5%) in group A, 9 (90%) in group B, 14 (73.5%) in group C. Median PFS was 129.5 days (range 82-532) in group A, 75 days (range 35-203) in group B, 136 days (range 59-514) in group C. Forty-seven patients (76%) had died at the time of the analysis, 22 (66.5%) in group A, 7 (70%) in group B, 18 (94.5%) in group C. Median OS was 345 days (range 65-1824) in group A, 174.5 days (range 50-1361) in group B, 409 days (range 102-1244) in group C. 52 MRI scans were available for central review: pseudoprogression was documented in 9 patients (29%) in group A, 0 (0%) in group B, and 5 (29.5%) in group C. Response rates were similar with all three sets of response criteria. Progressive disease was less often called when applying iRANO to assess SRT target lesions. While the retrospective nature and small sample size for subgroups are major limitations of this study, these data may indicate that the omission of SRT from first-line treatment may compromise outcome. Pseudoprogression is uncommon with immunotherapy alone; pseudoprogression rates were similar after SRT alone or in combination with immunotherapy or other systemic treatment. University Hospital of Zurich. Has not received any funding. All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]