External irradiation models for intracranial 9L glioma studies

<p>Abstract</p> <p>Purpose</p> <p>Radiotherapy has been shown to be an effective for the treatment human glioma and consists of 30 fractions of 2 Gy each for 6-7 weeks in the tumor volume with margins. However. in preclinical studies, many different radiation schedules are used. The main purpose of this work was to review the relevant literature and to propose an external whole-brain irradiation (WBI) protocol for a rat 9L glioma model.</p> <p>Materials and methods</p> <p>9L cells were implanted in the striatum of twenty 344-Fisher rats to induce a brain tumor. On day 8, animals were randomized in two groups: an untreated group and an irradiated group with three fractions of 6 Gy at day 8, 11 and 14. Survival and toxicity were assessed.</p> <p>Results</p> <p>Irradiated rats had significantly a longer survival (p = 0.01). No deaths occurred due to the treatment. Toxicities of reduced weight and alopecia were increased during the radiation period but no serious morbidity or mortality was observed. Moreover, abnormalities disappeared the week following the end of the therapeutic schedule.</p> <p>Conclusions</p> <p>Delivering 18 Gy in 3 fractions of 6 Gy every 3 days, with mild anaesthesia, is safe, easy to reproduce and allows for standardisation in preclinical studies of different treatment regimens glioma rat model.</p

Analyse des résultats de la radiothérapie tridimensionnelle conformationnelle par photons et protons de 60 chordomes de la base du crâne et du rachis cervical haut

L' objectif est de définir la faisabilité d un protocole d irradiation par photons-protons avec adaptation de la dose selon des facteurs dosimétriques ; et les facteurs pronostiques de contrôle local et de survie sans récidive chez des patients porteurs d un chordome de la base du crâne. Les méthodes : entre mai 2006 et juin 2008, 60 patients d âge médian 46.70 ans [10.8-79.2] (homme/femme 55/45%) on été traité par une combinaison de photons et de protons de hautes énergies. La composante proton a été délivrée par un faisceau de 201 MeV au centre de protonthérapie d Orsay. La dose médiane au GTV (gross tumor volume) était de 69.1 GyECo [56.6-82.7]. Résultats : Les médianes de suivi clinique et radiologique étaient de 19.48 mois [6.13-34.2].et 18.85 mois [1.67-32.73]. Cinq tumeurs ont récidivé localement et une à distance (pulmonaire et ganglionnaire). Les taux de contrôle local à 1, 2 ans étaient de 99% et 82%, respectivement. En analyse uni factorielle, le nombre de nerfs crâniens atteints (1 versus >1) (p=0.026), l atteinte cervicale (p=0.016), le volume du GTV (p=0.01607) étaient des facteurs significatifs de contrôle local. Le taux de survie sans récidive globale à 1 an était de 98%. En analyse uni factorielle, le nombre de nerfs crâniens touchés (inf. ou égal à 1) (p=0.08), l atteinte cervicale (p=0.002), le volume du GTV (p=0.009) étaient des facteurs significatifs de survie sans récidive globale. Vingt patients (33.33%) ont eu une ou des complications tardives : 5 cas (9%) de grade supérieur ou égal à 3 rapportés. Conclusion : cette étude souligne la faisabilité d un tel protocole d adaptation de dose tant en termes d efficacité que de tolérance. Le délai de suivi étant insuffisant, les comparaisons avec les résultats des autres équipes restent très prudentes.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Assessment of Radiation-Induced Optic Neuropathy in a Multi-Institutional Cohort of Chordoma and Chondrosarcoma Patients Treated with Proton Therapy

Radiation-induced optic neuropathy (RION) is a rare side effect following radiation therapy involving the optic structures whose onset is, due to the low amount of available data, challenging to predict. We have analyzed a multi-institutional cohort including 289 skull-base cancer patients treated with proton therapy who all received >45 GyRBE to the optic apparatus. An overall incidence rate of 4.2% (12) was observed, with chordoma patients being at higher risk (5.8%) than chondrosarcoma patients (3.2%). Older age and arterial hypertension, tumor involvement, and repeated surgeries (>3) were found to be associated with RION. Based on bootstrapping and cross-validation, a NTCP model based on age and hypertension was determined to be the most robust, showing good classification ability (AUC-ROC 0.77) and calibration on our dataset. We suggest the application of this model with a threshold of 6% to segment patients into low and high-risk groups before treatment planning. However, further data and external validation are warranted before clinical application

Dosimetric study between a single isocenter dynamic conformal arc therapy technique and Gamma Knife radiosurgery for multiple brain metastases treatment: impact of target volume geometrical characteristics

International audiencePurpose: To compare linac-based mono-isocentric radiosurgery with Brainlab Elements Multiple Brain Mets (MBM) SRS and the Gamma Knife using a specific statistical method and to analyze the dosimetric impact of the target volume geometric characteristics. A dose fall-off analysis allowed to evaluate the Gradient Index relevancy for the dose spillage characterization.Material and methods: Treatments were planned on twenty patients with three to nine brain metastases with MBM 2.0 and GammaPlan 11.0. Ninety-five metastases ranging from 0.02 to 9.61 cc were included. Paddick Index (PI), Gradient Index (GI), dose fall-off, volume of healthy brain receiving more than 12 Gy (V12Gy) and DVH were used for the plan comparison according to target volume, major axis diameter and Sphericity Index (SI). The multivariate regression approach allowed to analyze the impact of each geometric characteristic keeping all the others unchanged. A parallel study was led to evaluate the impact of the isodose line (IDL) prescription on the MBM plan quality.Results: For mono-isocentric linac-based radiosurgery, the IDL around 70-75% was the best compromise found. For both techniques, the GI and the dose fall-off decreased with the target volume. In comparison, PI was slightly improved with MBM for targets 0.78. GI was improved with GP for targets 0.4 cc or SI 5 cc against 6.5 cc with GP. The presence of OAR close to the PTV had no impact on the dose fall off values. The dose fall-off was higher for volumes < 3.8 cc with GP which had the sharpest dose fall-off in the infero-superior direction up to 30%/mm. The mean beam-on time was 94 min with GP against 13 min with MBM.Conclusions: The dose fall-off and the V12Gy were more relevant indicators than the GI for the low dose spillage assessment. Both evaluated techniques have comparable plan qualities with a slightly improved selectivity with MBM for smaller lesions but with a healthy tissues sparing slightly favorable to GP at the expense of a considerably longer irradiation time. However, a higher healthy tissue exposure must be considered for large volumes in MBM plans

Prise en charge de la douleur au cours des procédures invasives en cancérologie :efficacité et acceptabilité du mélange inhalé 50 % N2O/O2 (MEOPA)

Inhaled 50% N2O/O2 premix efficacy and safety, in addition to usual treatment, during painful procedures in oncology, was evaluated in a double-blind randomised study performed in patients ≥18 years. Initial and maximum pain during the procedure experienced by the patient was assessed using a visual analogical scale (VAS). Thirty percent of 199 patients suffered from a permanent background pain. Maximum pain felt by the patients during the invasive procedure was 10 mm lower in the 50% N2O/O 2 premix group vs the placebo group (p < 0.01). Feasibility by patient and medical team was greater than 89%. This study shows that administration of 50% N2O/O2 premix is an efficient, well-tolerated complement with good feasibility, according to the patient and medical team. © 2010 Médecine et Hygiène et Springer-Verlag France.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Primary CNS lymphoma of the corpus callosum: presentation and neurocognitive outcomes

International audienc

Surgery and protontherapy in Grade I and II skull base chondrosarcoma: A comparative retrospective study.

OBJECTIVE:Skull base chondrosarcoma is a rare tumour usually treated by surgery and proton therapy. However, as mortality rate is very low and treatment complications are frequent, a less aggressive therapeutic strategy could be considered. The objective of this study was to compare the results of surgery only vs surgery and adjuvant proton therapy, in terms of survival and treatment adverse effects, based on a retrospective series. METHODS:Monocentric retrospective study at a tertiary care centre. All patients treated for a skull base grade I and II chondrosarcoma were included. We collected data concerning surgical and proton therapy treatment and up-to-date follow-up, including Common Terminology Criteria for Adverse Events (CTCAE) scores. RESULTS:47 patients (23M/24F) were operated on between 2002 and 2015; mean age at diagnosis was 47 years-old (10-85). Petroclival and anterior skull base locations were found in 34 and 13 patients, respectively. Gross total resection was achieved in 17 cases (36%) and partial in 30 (64%). Adjuvant proton therapy (mean total dose 70 GyRBE,1.8 GyRBE/day) was administered in 23 cases. Overall mean follow-up was 91 months (7-182). Of the patients treated by surgery only, 8 (34%) experienced residual tumour progression (mean delay 51 months) and 5 received second-line proton therapy. Adjuvant proton therapy was associated with a significantly lower rate of relapse (11%; p = 0.01). There was no significant difference in 10-year disease specific survival between patients initially treated with or without adjuvant proton therapy (100% vs 89.8%, p = 0.14). Difference in high-grade toxicity was not statistically significant between patients in both groups (25% (7) vs 11% (5), p = 0.10). The most frequent adverse effect of proton therapy was sensorineural hearing loss (39%). CONCLUSION:Long-term disease specific survival was not significantly lower in patients without adjuvant proton therapy, but they experienced less adverse effects. We believe a surgery only strategy could be discussed, delaying as much as possible proton therapy in cases of relapse. Further prospective studies are needed to validate this more conservative strategy in skull base chondrosarcoma

Impact du mouvement des nerfs optiques en fonction de l’orientation du regard sur la radiothérapie des tumeurs intra-orbitaires

International audiencePurpose: Management of inter- and intra-fraction movements of target volumes and organs at risk (OARs) during radiotherapy is essential. While there is little OAR or target volume movement, the movements and orientation of the eyes can be significant during radiotherapy and they can affect the position of the optic nerve. The objective of the present study was to assess the variations of the optic nerve position due to gaze direction and to discuss their clinical consequences on the radiation treatment of intraorbital tumors.Material and methods: Three patients without a history of oculomotor nerve palsy underwent six CT acquisitions with a thermoplastic mask: eyes open with different gaze directions (straight ahead, left, right, up, down) and eyes closed. The acquisition with the straight-ahead gaze was chosen as the reference position. Left and right optic nerves were segmented on the six acquisitions, and total volumes and maximum amplitude motions were calculated in three dimensions.Results: Maximum differences were observed while looking left and up, with a median maximum amplitude of 5 and 6mm [range: 2-7mm], respectively. These motions induced a position variation of more than 50% of the volume of the optic nerve (compared to the reference position). Greater variations of motion were observed for the anterior portion of the nerve. The gaze position with the fewest variations compared to the reference position was eyes closed.Conclusion: Optic nerve positions vary significantly due to the gaze direction, especially for the anterior portion of the nerve. These variations should be taken into account for the treatment of small intraorbital tumors involving the anterior third of the optic nerve.Objectif de l’étudeLa gestion des mouvements inter- et intra-fractions des volumes cibles et des organes à risque pendant la radiothérapie est essentielle. Bien qu’il y ait peu de mouvements des OAR ou des volumes cibles, les mouvements et l’orientation des yeux peuvent être significatifs pendant la radiothérapie et ils peuvent affecter la position du nerf optique. L’objectif de cette étude était d’évaluer les variations de la position du nerf optique dues à la direction du regard et de discuter des conséquences cliniques sur la radiothérapie des tumeurs intra-orbitaires.Matériel et méthodesTrois patients sans antécédents de paralysie du nerf oculomoteur ont eu six acquisitions scanographiques avec un masque thermoplastique: yeux ouverts avec différentes directions du regard (droit devant, gauche, droite, haut, bas) et yeux fermés. L’acquisition avec le regard droit devant a été choisie comme position de référence. Les nerfs optiques gauche et droit ont été segmentés sur les six acquisitions, les volumes totaux et les mouvements d’amplitude maximale ont été calculés en trois dimensions.RésultatsLes différences maximales ont été observées en regardant vers la gauche et vers le haut, avec des amplitudes maximales médianes de 5 et 6 mm [2–7 mm]. Ces mouvements ont induit une variation de position de plus de 50 % du volume du nerf optique (par rapport à la position de référence). Des variations de mouvement plus importantes ont été observées pour la partie antérieure du nerf. Très peu de variations de mouvement étaient observées quand le patient avait les yeux fermés.ConclusionLes positions du nerf optique varient significativement en fonction de la direction du regard, en particulier pour la partie antérieure du nerf. Ces variations doivent être prises en compte pour le traitement des petites tumeurs intra-orbitaires impliquant le tiers antérieur du nerf optique

Primary vitreoretinal lymphoma: short review of the literature, results of a European survey and French guidelines of the LOC network for diagnosis, treatment and follow-up

International audiencePurpose of review. The aim of this study was to highlight the diagnostic and management challenges of primary vitreoretinal lymphoma (PVRL) through a review of the literature and a European survey on real-life practices for PVRL.Recent findings. The care of PVRL patients is heterogeneous between specialists and countries. Upfront systemic treatment based on highdose methotrexate chemotherapy, with or without local treatment, might reduce or delay the risk of brain relapse. Ibrutinib, lenalidomide with or without rituximab, and temozolomide are effective for patients with relapsed/refractory PVRL and should be tested as first-line treatments.Summary. The prognosis of PVRL remains dismal. No firm conclusion regarding optimal treatment can yet be drawn. The risk of brain relapse remains high. Diagnostic procedures and assessment of therapeutic responses need to be homogenized. Collaboration between specialists involved in PVRL and multicentric prospective therapeutic studies are strongly needed. The recommendations of the French group for primary oculocerebral lymphoma (LOC network) are provided, as a basis for further European collaborative work