[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.

[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.

Descriptive epidemiology of CNS tumors in France: results from the Gironde Registry for the period 2000-2007.

An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry provides here the first data on CNS tumor incidence and trends in France for all histological types, including benign and malignant tumors, for the period 2000-2007. Incidence rates were calculated globally and for each histological subtype. For trends, a piecewise log-linear model was used. The overall annual incidence rate was found to be 17.6/100 000. Of this rate, 7.9/100 000 were neuroepithelial tumors and 6.0/100 000 were meningiomas. An overall increase in CNS tumor incidence was observed from 2000 to 2007, with an annual percent change (APC) of +2.33%, which was explained mainly by an increase in the incidence of meningiomas over the 8-year period (APC = +5.4%), and also more recently by an increase in neuroepithelial tumors (APC = +7.45% from 2003). The overall increase was more pronounced in women and in the elderly, with an APC peaking at +24.65% in subjects 85 and over. The increase in the incidence rates we observed may have several explanations: not only improvements in registration, diagnosis, and clinical practice, but also changes in potential risk factors.

[Epidemiology of glioblastoma]. / Épidémiologie des glioblastomes.

An increasing incidence of glioblastoma has been observed over the last 30 years. Improvements in diagnostic tools such as CT scans and MRI, changes observed in histological classifications, and adjustments in neurosurgical practices have contributed substantially to this increase. Moreover, the aging of the population and the increasing occurrence of glioblastoma beyond 60 years of age are additional explanations. In Gironde (France), where a specialized registry has been established, the annual incidence of glioblastoma is 4.96/100,000. Wide geographic variations are observed, possibly linked to ethnicity. However, the role of intrinsic and/or extrinsic factors cannot be ruled out. Comparing data between registries is difficult and requires taking into account periods of recruitment and diagnostic tools. Ethnicity, age, sex, hereditary syndromes, some constitutive polymorphisms, and brain irradiation are the established risk factors Allergies or asthma, certain viral infections, autoimmune diseases, nonsteroidal anti-inflammatory drug intake, substitutive hormonal therapy, and dietary antioxidant intake are the established protective factors. Many studies on electromagnetic fields - in particular cellular phones - pesticides, solvents, and other factors have been published. Until now, the results are discordant or are not confirmed because of methodological limitations. Future studies combining constitutive polymorphisms and exposure assessment are likely to provide consistent and important data that will improve our knowledge in the epidemiology of glioblastoma.

[Normal tissue tolerance to external beam radiation therapy: peripheral nerves]. / Dose de tolérance à l'irradiation des tissus sains: les nerfs périphériques.

Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy...) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications.

[Normal tissue tolerance to external beam radiation therapy: adult bone]. / Dose de tolérance à l'irradiation des tissus sains: l'os chez l'adulte.

Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably underevaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume.

[Molecular imaging of tumor hypoxia]. / Imagerie moléculaire de l'hypoxie tumorale.

By allowing an earlier diagnosis and a more exhaustive assessment of extension of the disease, the tomography by emission of positrons (TEP) transforms the care of numerous cancers. At present, (18)F-fluorodesoxyglucose ([(18)F]-FDG) imaging appears as the only one available but new molecular markers are being developed. In the next future they would modify the approach of cancers. In this context, the molecular imaging of the hypoxia and especially the (18)Ffluoromisonidazole TEP ([(18)F]-MISO TEP) can give supplementary information allowing the mapping of hypoxic regions within the tumour. Because of the links, which exist between tumour hypoxia and treatment resistance of very numerous cancers, this information can have an interest, for determination of prognosis as well as for the delineation, volumes to be irradiated. Head and neck tumours are doubtless those for which the literature gives the most elements on the therapeutic impact of tumour hypoxia. Targeted therapies, based on hypoxia, already exist and the contribution of the molecular imaging could be decisive in the evaluation of the impact of such treatment. Molecular imaging of brain tumours remains to be developed. The potential contributions of the [(18)F]-MISO TEP for the care of these patients need to be confirmed. In this context, we propose a review of hypoxia molecular imaging taking as examples head and neck tumours and glioblastomas (GB), two tumours for which hypoxia is one of the key factors to overcome in order to increase therapeutics results.

[Repositioning accuracy of cerebral fractionated stereotactic radiotherapy using CT scanning]. / Evaluation par tomodensitométrie du repositionnement en radiothérapie stéréotaxique fractionnée cérébrale.

PURPOSE: To evaluate the accuracy of patient repositioning in fractionated cerebral stereotactic radiotherapy using a Brain Lab stereotactic cranial mask in conjunction with standard dental fixation. PATIENTS AND METHODS: Fifty planning and checking CT scans were performed in 25 patients. The check CT scan was performed before or after one of the three sessions of treatment. Coregistration to the planning CT scan was used to assess alignment of the isocentre to the reference markers. The relative position of the PTV with regard to isocentre allowed us to determine its total displacement (3D vector). RESULTS: Mean isocentre translations (+/-SD) taking into account direction were -0.01+/-0.7, -0.2+/-1.3 and 0.07+/-0.5mm in mediolateral, craniocaudal and anteroposterior directions respectively. Mean rotations (+/- SD) were -0.02+/-0.6, -0.08+/-0.3 and -0.1+/-0.3 degree in mediolateral, craniocaudal and anteroposterior axes respectively. Mean overall PTV displacement was 1.8+/-1.5mm. PTV displacement was smaller than 2 and 3mm in 19/25 and 23/25 patients respectively. CONCLUSION: The accuracy of patient positioning using a stereotactic cranial mask system is similar to those reported in the literature and shows a satisfactory reproducibility with a standard dental fixation.

[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.

Verifying patient identity and site of surgery: improving compliance with protocol by audit and feedback.

BACKGROUND: The potential severity of wrong patient/procedure/site of surgery and the view that these events are avoidable, make the prevention of such errors a priority. An intervention was set up to develop a verification protocol for checking patient identity and the site of surgery with periodic audits to measure compliance while providing feedback. ASSESSMENT OF PROBLEM: A nurse auditor performed the compliance audits in inpatients and outpatients during three consecutive 3-month periods and three 1-month follow-up periods; 11 audit criteria were recorded, as well as reasons for not performing a check. STRATEGY FOR CHANGE: The nurse auditor provided feedback to the health professionals, including discussion of inadequate checks. RESULTS: 1,000 interactions between patients and their anaesthetist or nurse anaesthetist were observed. Between the first and second audit periods compliance with all audit criteria except "surgical site marked" noticeably improved, such as the proportion of patients whose identities were checked (62.6% to 81.4%); full compliance with protocol in patient identity checks (9.7% to 38.1%); proportion of site of surgery checks carried out (77.1% to 92.6%); and full compliance with protocol in site of surgery checks (32.2% to 52.0%). Thereafter, compliance was stable for most criteria. The reason for failure to perform checks of patient identity or site of surgery was mostly that the anaesthetist in charge had seen the patient at the preanaesthetic consultation. LESSONS AND MESSAGES: By combining the implementation of a verification protocol with periodic audits with feedback, the intervention changed practice and increased compliance with patient identity and site of surgery checks. The impact of the intervention was limited by communication problems between patients and professionals, and lack of collaboration with surgical services.

[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.

Neoadjuvant phase II multicentre study of new agents in patients with malignant glioma after minimal surgery. Report of a cohort of 187 patients treated with temozolomide.

BACKGROUND: The aim of this study was to assess the efficacy of new agents in patients with malignant glioma in a neoadjuvant setting not confounded by surgery. The first study of neoadjuvant temozolomide aimed to provide a benchmark for future evaluation of new treatments. PATIENTS AND METHODS: This was a multicentre phase II study of chemotherapy in patients with histologically verified glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) who had undergone biopsy alone. Patients were planned to receive two cycles of temozolomide at 200 mg/m(2) orally daily for 5 days at a 28-day interval prior to radiotherapy. Response was assessed by two central observers on pre- and post-chemotherapy enhanced scans using bi-dimensional criteria and as progression-free survival (PFS) at the time of second assessment prior to radiotherapy. Withdrawal from the study due to worsening clinical condition was, in the absence of second imaging, assessed as progressive disease. Survival and quality of life (QOL) were secondary endpoints. RESULTS: Between August 1999 and June 2002, 188 patients from 15 UK and two Italian centres were entered into the study and 187 were analysed. Overall, 162 patients were assessable for response; seven had partial and 25 had minimal response. The objective response rate was 20% [95% confidence interval (CI) 14-26%] and PFS prior to commencing radiotherapy was 64% (95% CI 57-72%). The median survival was 10 months, and 1-year survival 41%. The median survival of responders was 16 months compared to 3 months in patients with progressive disease (P <0.001 on multivariate analysis). CONCLUSION: The phase II study design of primary chemotherapy in patients with malignant glioma following biopsy alone is feasible and provides as objective a method of assessment of efficacy as is currently available. The baseline data on temozolomide provide a benchmark for assessment of efficacy of other agents and combinations.

[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.