[Prospective longitudinal study on the evolution of autobiographical memory in patients irradiated for benign skull base tumour]. / Étude prospective longitudinale sur l'évolution de la mémoire autobiographique de patients irradiés pour une tumeur bénigne de la base du crâne.

PURPOSE: Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory. PATIENTS AND METHODS: From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1year and 2years post-treatment. Neuropsychological tests were converted to Z-Score for comparability. RESULTS: Twelve of the 19 patients included had a complete neuropsychological evaluation at 2years and were analysed. On the "TEMPau" test, no significant difference in autobiographical memory was found at 2years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study. CONCLUSION: Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results.

Spontaneous resolution of intracranial hypertension following radiotherapy for posterior parasagittal meningioma: About two cases and review of the literature.

We report the cases of two patients who underwent normofractionated radiotherapy for evolutive asymptomatic parasagittal meningiomas. After completion of radiotherapy, both patients presented severe headache and vomiting episodes without papillar edema. We then decided a "wait-and-scan" strategy because of the slit-ventricles, and symptoms regressed spontaneously. MRI showed significant tumor regression a year after radiotherapy with a newly developed collateral venous drainage system in the first patient and a left, unusually large, superior anastomotic vein in the second. These clinical presentation and radiological evolution are compatible with venous stenosis caused by radiation-induced symptomatic edema, fading after the development of a collateral venous drainage system. The relation between pressure-related headaches and venous anatomy remains unclear in parasagittal meningiomas. These observations underline the importance of the study of venous anatomy when pressure-related headaches are suspected. Further clinical descriptions might help the clinicians to treat these patients' symptoms.

[Stereotactic radiotherapy of non-tumoral brain pathologies: Arteriovenous malformations and trigeminal neuralgias]. / Radiothérapie stéréotaxique des affections cérébrales non tumorales : malformations artérioveineuses et névralgies trigéminales.

Stereotactic radiotherapy and radiosurgery allow delivery of high irradiation doses in a limited volume. These techniques are specially adapted to brain and nervous pathologies. Indication are not only cancers and tumors but also non tumor tissues such as arteriovenous malformations. In some case purpose of stereotactic radiotherapy is solely functional, for example for trigeminal neuralgia. We detail the questions that raise treatment of these non-tumor pathologies. These pathologies imply a multidisciplinary approach that associate radiation oncologists, neuro-radiologist and neurosurgeons.

[Acupuncture and smoking cessation, a review of the literature]. / Acupuncture et arrêt de la consommation tabagique, une revue de la littérature.

INTRODUCTION: Tobacco smoking represents the main cause of death in industrialised countries. Acupuncture is proposed as an aid to stopping smoking. What are the current studies? BACKGROUND: We found 23 controlled randomised studies with differing protocols in terms of intensity of treatment and methodology. The meta-analyses undertaken were contradictory. The short-term effect of acupuncture is well documented but the medium term effect is more uncertain. OUTLOOK: The undertaking of well-standardised, high-intensity protocols is necessary to produce evidence of a medium term effect. CONCLUSION: Acupuncture can be offered to patients wishing to stop smoking within the framework of a global management programme. The association of acupuncture with classical aids increases the chances of the patient stopping. The conditions of intervention should be defined precisely within the framework of a randomised controlled trial.

[Epidemiology of primary brain tumor]. / Epidémiologie des tumeurs cérébrales primitives.

Two main approaches are generally used to study the epidemiology of primary brain tumors. The first approach is to identify risk factors, which may be intrinsic or related to external causes. The second main approach is descriptive. Intrinsic factors potentially affecting risk include genetic predisposition and susceptibility, gender, race, birth weight and allergy. Radiation exposure is the main extrinsic factor affecting risk. A large body of work devoted, among others, to electromagnetic fields and especially cellular phones, substitutive hormonal therapy, pesticides, and diet have been published. To date, results have been discordant. Descriptive epidemiological studies have reported an increasing annual incidence of primary brain tumors in industrialized countries. The main reasons are the increasing age of the population and better access to diagnostic imaging. Comparing incidences from one registry to another is difficult. Spatial and temporal variations constitute one explanation and evolutions in coding methods another. In all registries, weak incidence of primary brain tumors constitute a very important limiting factor. Renewed interest from the neuro-oncological community is needed to obtain pertinent and essential data which could facilitate improved knowledge on this topic.

[Radiation therapy for glial tumors: technical aspects and clinical indications]. / Radiothérapie des tumeurs gliales: techniques et indications.

Radiotherapy of glial tumors is rapidly evolving with the recent technical and therapeutic progress. About technical aspects, progress in technical imaging and development of non-coplanar conformal and IMRT techniques provide new possibilities for sparing healthy tissue while increasing dose in tumoral volume. Furthermore, functional and molecular imaging are helpful for delineation and for prediction of relapse. Even modest, the actual improvement of survival with radiochemotherapy leads now to new and important developments for clinical research according to clinical data (age, general status), biological data (MGMT promotor methylation and cytogenetic modifications) and technical data (quality of surgery and radiotherapy). Understanding of molecular mechanisms allows for rational targeting or specific pathways of repair, signaling angiogenesis associated with surgery and radiotherapy in a multidisciplinary approach.

[Radiotherapy of adult glial tumors: new developments and perspectives]. / Radiothérapie des tumeurs gliales de l'adulte : actualités et perspectives.

Adult gliomas (WHO grade II, III and IV) are heterogeneous primitive brain tumors. The prognosis of these tumors depends on multiple factors such as age at diagnosis, Karnofsky score, histopathology, biology and treatments. Radiotherapy (RT) plays an important role in the treatment strategy, after surgery. RT has been evaluated in terms of survival, median time to progression and toxicity. Techniques of RT have improved, during the last two decades: neuro-imaging (CT-scan, MRI and PET) and dedicated computers for dosimetry make it possible to deliver an homogeneous dose in the target volume while sparing normal tissues. Photons X are usually delivered with stereotactic or conformational noncoplanar techniques. Total doses delivered range from 50.4 to 60 Gy (1.8-2 Gy/fraction). Median survivals are different with regard to the tumor grade. However, genetic and biological factors also are important prognostic factors such as inactivation of the MGMT gene for glioblastomas and loss of heterozygosity (LOH) 1p/19q, usually associated with pure oligodendroglioma. During the 1990s, temozolomide (TMZ) was specifically developed as a chemotherapy agent against primary brain tumors. The current TMZ/RT regimen in newly diagnosed GBM has been proposed as a standard treatment. The optimal treatment strategy is not known. New clinical trials are needed to assess new techniques of RT; a further improvement in medical treatment requires novel agents.

[Radiotherapy of benign intracranial tumors]. / Radiothérapie des tumeurs intracrâniennes bénignes.

Most of the benign intracranial tumors are meningiomas, vestibular schwannomas, pituitary adenomas, craniopharyngiomas, and glomus tumors. Some of them grow very slowly, and can be observed without specific treatment, especially if they are asymptomatic. Symptomatic or growing tumors are treated by surgery, which is the reference treatment. When surgery is not possible, due to the location of the lesion, or general conditions, radiotherapy can be applied, as it is if there is a postoperative growing residual tumor, or a local relapse. Indications have to be discussed in polydisciplinary meetings, with precise evaluation of the benefit and risks of the treatments. The techniques to be used are the most modern ones, as multimodal imaging and image-guided radiation therapy. Stereotactic treatments, using fractionated or single doses depending on the size or the location of the tumors, are commonly realized, to avoid as much a possible the occurrence of late side effects.

[Radiotherapy for paediatric cancers]. / Radiothérapie des cancers de l'enfant.

The purpose of this article is to describe the specificities of paediatric radiation oncology: cancer types, radiotherapy indications, techniques, organisation and reglementary framework.

[French organization of paediatric radiation treatment: Results of a survey conducted by the radiotherapy Committee of the French Society of Paediatric Cancers (SFCE)]. / Organisation française de la radiothérapie pédiatrique : résultats d'une enquête du comité radiothérapie de la Société française des cancers de l'enfant (SFCE).

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.

Paediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy.

BACKGROUND AND PURPOSE: Brain tumours are the most frequent solid tumours in children and the most frequent radiotherapy indications in paediatrics, with frequent late effects: cognitive, osseous, visual, auditory and hormonal. A better protection of healthy tissues by improved beam ballistics, with particle therapy, is expected to decrease significantly late effects without decreasing local control and survival. This article reviews the scientific literature to advocate indications of protontherapy and carbon ion therapy for childhood central nervous system cancer, and estimate the expected therapeutic benefits. MATERIALS AND METHODS: A systematic review was performed on paediatric brain tumour treatments using Medline (from 1966 to March of 2014). To be included, clinical trials had to meet the following criteria: age of patients 18 years or younger, treated with radiation, and report of survival. Studies were also selected according to the evidence level. A secondary search of cited references found other studies about cognitive functions, quality of life, the comparison of photon and proton dosimetry showing potential dose escalation and/or sparing of organs at risk with protontherapy; and studies on dosimetric and technical issues related to protontherapy. RESULTS: A total of 7051 primary references published were retrieved, among which 40 clinical studies and 60 papers about quality of life, dose distribution and dosimetry were analysed, as well as the ongoing clinical trials. These papers have been summarized and reported in a specific document made available to the participants of a final 1-day workshop. Tumours of the meningeal envelop and bony cranial structures were excluded from the analysis. Protontherapy allows outstanding ballistics to target the tumour area, while substantially decreasing radiation dose to the normal tissues. There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas. Carbon ion therapy is just emerging and may be studied for highly aggressive and radioresistant tumours, as an initial treatment for diffuse brainstem gliomas, and for relapse of high-grade gliomas. CONCLUSION: Both protontherapy and carbon ion therapy are promising for paediatric brain tumours. The benefit of decreasing late effects without altering survival has been described for most paediatric brain tumours with protontherapy and is currently assessed in ongoing clinical trials with up-to-date proton devices. Unfortunately, in 2015, only a minority of paediatric patients in France can receive protontherapy due to the lack of equipment.

Interaction between central alpha 1- and alpha 2-adrenoceptors on sympathetic tone in rats.

The interaction between piperoxan and alpha 2-agonists on sympathetic tone was studied in rats. The sympatho-inhibitory effect of alpha 2-agonists (clonidine, guanfacine, B-HT 933) was assessed by recording heart rate in normotensive bilaterally-vagotomized rats. Clonidine (3 micrograms/kg, i.c.v.) and B-HT 933 (100 micrograms/kg, i.c.v.) induced a bradycardia which was fully reversed by piperoxan (30 micrograms/kg, i.c.v.). However, in rats treated with guanfacine, piperoxan induced a partial recovery of the bradycardic effect. The injection of a small dose of the specific alpha 1-adrenoceptor blocking drug, AR-C 239 (10 micrograms/kg, i.c.v.) which, by itself did not modify heart rate, completely inhibited the reversal effect of piperoxan in rats treated with clonidine, B-HT 933 or guanfacine. In rat brainstem membranes, B-HT 933 was found to bind to both alpha 1- and alpha 2-adrenoceptors and was as potent as clonidine in competing for alpha 1-sites bound by [3H]prazosin. On the other hand, in bilaterally vagotomized rats, piperoxan (30 micrograms/kg, i.c.v.) induced an increase in blood pressure and heart rate which was inhibited by previous administration of AR-C 239 (10 micrograms/kg, i.c.v.). These data suggest that, by inhibiting central alpha 2-adrenoceptors, piperoxan unmasks central alpha 1-adrenoceptor stimulation by endogenous catecholamines leading to an increase in the sympathetic tone, but a full recovery in heart rate could be observed only with the mixed alpha 1- and alpha 2-adrenoceptor agonists, clonidine and B-HT 933. In addition, these data further indicate that alpha 1-adrenoceptors are implicated in a tonic control of the sympathetic nerve activity in normotensive rats.

Possible role of alpha 1- and alpha 2-adrenoceptors in the modulation of the sympathetic component of the baroreflex.

In anaesthetized and bilaterally vagotomized dogs, reflex bradycardia elicited by intravenous injection of noradrenaline was facilitated by AR-C 239, a new alpha 1-adrenoceptor blocking drug and inhibited by the alpha 2-adrenoceptor antagonist, yohimbine. Both alpha-blocking drugs were administered into the vertebral artery. In another group of bilaterally vagotomized dogs, unilateral electrical stimulation of the carotid sinus nerve induced a frequency-dependent decrease in mean blood pressure solely mediated through the sympatho-inhibitory component of the baroreflex. Administration of the alpha 1-adrenoceptor blocking drugs, AR-C 239 and prazosin (5 micrograms/kg) into the vertebral artery decreased basal mean blood pressure and increased depressor responses to the carotid sinus nerve stimulation, whereas the intracisternal injection of phenylephrine (30 micrograms/kg), a preferential alpha 1-agonist, increased mean blood pressure but inhibited the hypotension resulting from electrical stimulation. In addition, the injection into the vertebral artery of yohimbine (100 micrograms/kg), an alpha 2-adrenoceptor blocking agent which caused no change in mean arterial pressure, inhibited the decrease in the sympathetic component. In conclusion, these results suggest the possible participation of the two types of alpha-adrenoceptors in the modulation of the sympathetic component of the baroreflex: alpha 1-adrenoceptor stimulation could inhibit, whereas alpha 2-adrenoceptor activation facilitates the reflex activity in the sympathetic fibres.

Characterization of dihydropyridine binding sites in the rat brain: hypertension and age-dependent modulation of [3H](+)-PN 200-110 binding.

The properties of [3H]dihydropyridine (DHP), nitrendipine and (+)-PN 200-110, binding to rat cerebral membranes were investigated. In normotensive Wistar-Kyoto (WKY) adult rats, the highest densities of [3H]DHP binding sites were found in the hippocampus. Frontal cerebral cortex and hypothalamus had intermediate levels and no specific binding of [3H]DHP and [125I]iodipine could be detected in the brainstem membranes and more precisely in the nucleus tractus solitarius and in the locus coeruleus. Changes in the maximal number of DHP binding sites (Bmax) were observed in spontaneously hypertensive rats (SHR) and in old Sprague-Dawley rats. In adult SHR, there was a significant increase in the Bmax values of [3H](+)-PN 200-110 binding in the hippocampus when compared to the values obtained in WKY. There was no difference in the Bmax values between young (3 weeks) prehypertensive SHR and age-matched WKY. In senescent (26 months) Sprague-Dawley rats, the Bmax values of [3H](+)-PN 200-110 binding were significantly reduced (30%) in the frontal cerebral cortex and the hippocampus, as compared with the number of DHP binding sites found in mature Sprague-Dawley rats (15 weeks).

Role of alpha 1- and alpha 2-adrenoceptors in the modulation of the baroreflex vagal bradycardia.

Yohimbine (100 micrograms/kg), an alpha 2-adrenoceptor blocking agent when injected into the vertebral artery of anaesthetized dogs decreased the vagally mediated bradycardia induced by carotid sinus nerve stimulation. Intracisternal administration of phenylephrine (30 micrograms/kg) an alpha 1-adrenoceptor agonist decreased, whereas AR-C 239 (5 micrograms/kg) and prazosin (5 micrograms/kg) two potent alpha 1-adrenoceptor antagonists injected into the vertebral artery, potentiated the bradycardiac response. These results suggest the presence of two types of alpha-adrenoceptors to modulate the baroreceptor pathway: alpha 1-adrenoceptors inhibit and alpha 2-adrenoceptors facilitate the transmission of baroreceptor impulses.

Possible role of central alpha 1-adrenoceptors in the control of the autonomic nervous system in normotensive and spontaneously hypertensive rats.

The cardiovascular effects of AR-C 239, a new and selective alpha 1-adrenoceptor blocking drug were studied in normotensive and spontaneously hypertensive rats (SHR). AR-C 239 (300 micrograms/kg i.v.) did not change the heart rate in control (without pretreatment) and bilaterally vagotomized normotensive rats, but induced significant bradycardia in rats pretreated with a beta-adrenoceptor blocking drug. This bradycardic effect was inhibited by atropine or bilateral vagotomy. In SHR, the administration of AR-C 239 reduced heart rate in the control, bilaterally vagotomized and beta-blocked rats. Blood pressure was decreased in the same way in the two rat strains. It is suggested that central alpha 1-adrenoceptors could participate in the control of vagal tone in normotensive and SH rats, and of sympathetic activity in the SHR only.

Central alpha 1-adrenoceptors and cardiovascular control in normotensive and spontaneously hypertensive rats.

Intracerebroventricular (i.c.v.) injections of AR-C 239 (30 micrograms/kg), a selective alpha 1-adrenoceptor blocking drug, did not modify the heart rate in normotensive control (without pretreatment), bilaterally vagotomized and beta blocked rats and in spontaneously hypertensive (SH) bilaterally vagotomized rats. Intracisternal (i.c.) administrations of AR-C 239 (30 micrograms/kg) however decreased the heart rate in normotensive beta blocked and in SH bilaterally vagotomized rats. The differential effect on heart rate of i.c.v. versus i.c. administration of AR-C 239 suggests a brainstem localization of the alpha 1-adrenoceptors involved. The binding of [3H]prazosin was significantly higher in homogenates from whole brain and in membranes from the cerebral cortex and hypothalamus of SH rats as compared to normotensive rats. In addition, the binding of [125I]BE 2254, a new iodinated radioligand of high specific radioactivity used to characterize alpha 1-adrenoceptors, was significantly increased in membranes from the NTS of SH rats. These results suggest that central alpha 1-adrenoceptors localized in the brainstem and in the hypothalamus and the cortex play a role in the control of vagal tone in normotensive rats and of sympathetic activity in SH animals. Thus, it is postulated that central alpha 1-adrenoceptors may participate in either the genesis or the maintenance of genetic hypertension.

Effects of L-glutamic acid and kainic acid on central cardiovascular control.

L-Glutamic acid and kainic acid injected into the cisterna magna of dogs, produced a dose-dependent increase in blood pressure and a decrease in heart rate. In contrast, intravenous injection of both compounds was ineffective. The hypertension was probably due to an increase in sympathetic tone as guanethidine prevented the rise in blood pressure induced by central administration of L-glutamic acid and kainic acid. Kainic acid was 1 000 fold more potent than L-glutamic acid.

[Postoperative radiotherapy of a benign tumor of the ankle]. / Radiothérapie postopératoire d'une tumeur bénigne de la cheville.

Pigmented villonodular synovitis is a rare benign tumor. The high rate or recurrence after surgery exposes the risk of non-conservative or non-functional treatment. External irradiation of post-surgical residual disease seems to be useful for the prevention of relapse and conservation with a good functional result. We report a clinical observation of a case with a diffuse type of pigmented villonodular synovitis of the ankle, operated on three times, and then treated by external irradiation. The published results in terms of response and functional prognosis of 14 cases of multi-recurrent villonodular synovitis treated by irradiation seem to confirm this therapeutic option.

[Volume-effect and radiotherapy [II]. Part II: volume-effect and normal tissue]. / Effet volume en radiothérapie [II]. Deuxième partie : volume et tolérance des tissus sains.

The first part of our work has focused on the relationship between tumor volume and tumor control. Indeed, it is well known that the importance of irradiated volume could be a main parameter of radiation-induced complications. Numerous mathematical models have described the correlation between the irradiated volume and the risk of adverse effects. These models should predict the complication rate of each treatment planning. At the present time late effects have been the most studied. In this report we firstly propose a review of different mathematical models described for volume effect. Secondly, we will discuss whether these theoretical considerations can influence our view of radiation treatment planning optimization.