Search

Poster: Clinical track: Breast PO-0974: Helical intensity-modulated radiation therapy for locally advanced breast cancer:a prospective study B. Bataille, F. Le Tinier, R. Bennadji, L. Basson, A. Escande, E. Tresch, F. Crop, F. Darloy, D. Carlier, X. Mirabel, E. Lartigau, D. Pasquier. [Extracted from the article]

Background and Objectives: Different mechanisms have been proposed to explain spinal anesthesia failure even after LA injection into the subarachnoid space. The aim of this prospective multicenter study was to assess the incidence of spinal anesthesia failure, excluding technical problems, and then to suggest independent factors leading to failure.Methods: Consecutive spinal anesthetic procedures performed in 21 centers were included. Exclusion criteria were contraindications to spinal anesthesia and technical difficulties. Primary end point was the calculation of failure incidence. Factors leading to spinal anesthesia failure were investigated.Results: One thousand two hundred fourteen spinals were included. Failure rate, reported by 17 of 21 centers, was 3.2% (95% confidence interval [CI], 2.2-4.2). A total failure (no sensory block) was noted in 41% of the 39 cases of failed block. Patients in the failure group were younger as compared with patients in the success group. Using backward logistic regression, factors associated with failure were the number of puncture attempts at 3 or more (odds ratio [OR], 2.86; 95% CI, 1.20-6.79) and the absence of the use of an adjuvant medication with the local anesthetic injected (OR, 2.32; 95% CI, 1.2-4.5). Age older than 70 years (OR, 0.3; 95% CI, 0.20-0.93) was associated with a decrease of failure.Conclusions: The results of this study showed that the incidence of spinal anesthesia failure was 3.2%. The number of puncture attempts at 3 or more and the absence of adjuvant medication associated with local anesthetic were independent factors associated with the increased risk of failure. The failure of spinal anesthesia was rare in patients older than 70 years. [ABSTRACT FROM AUTHOR]

This study assessed the prognostic value of several markers involved in gliomagenesis, and compared it with that of other clinical and imaging markers already used. Four-hundred and sixteen adult patients with newly diagnosed glioma were included over a 3-year period and tumour suppressor genes, oncogenes, MGMT and hTERT expressions, losses of heterozygosity, as well as relevant clinical and imaging information were recorded. This prospective study was based on all adult gliomas. Analyses were performed on patient groups selected according to World Health Organization histoprognostic criteria and on the entire cohort. The endpoint was overall survival, estimated by the Kaplan-Meier method. Univariate analysis was followed by multivariate analysis according to a Cox model. p14(ARF), p16(INK4A) and PTEN expressions, and 10p 10q23, 10q26 and 13q LOH for the entire cohort, hTERT expression for high-grade tumours, EGFR for glioblastomas, 10q26 LOH for grade III tumours and anaplastic oligodendrogliomas were found to be correlated with overall survival on univariate analysis and age and grade on multivariate analysis only. This study confirms the prognostic value of several markers. However, the scattering of the values explained by tumour heterogeneity prevents their use in individual decision-making. [ABSTRACT FROM AUTHOR]

Glial tumours are a devastating, poorly understood condition carrying a gloomy prognosis for which clinicians sorely lack reliable predictive parameters facilitating a sound treatment strategy. Tp73, a p53 family member, expresses two main classes of isoforms--transactivatory activity (TA)p73 and DeltaTAp73--exhibiting tumour suppressor gene and oncogene properties, respectively. The authors examined their expression status in high- and low-grade adult gliomas. Isoform-specific real-time reverse transcription-polymerase chain reaction was used for the analysis of Tp73 isoform transcript expression in a series of 51 adult patients harbouring glial tumours, in order to compare tumour grades with each other, and with non-tumoural samples obtained from epileptic patients as well. Our data demonstrate increase of TAp73 and DeltaTAp73 transcript levels at onset and early stage of the disease. We also show that DeltaEx2-3 isoform expression in low-grade tumours anticipates clinical and imaging progression to higher grades, and correlates to the patients' survival. Expression levels of P1 promoter generated Tp73 isoforms--and particularly DeltaEx2-3--indeed allow for prediction of the clinical progression of low-grade gliomas in adults. Our data are the first such molecular biology report regarding low-grade tumours and as such should be of help for sound decision-making. [ABSTRACT FROM AUTHOR]

The present work investigates the preparation and the release of acetaminophen from spray-dried microparticles. Two cellulose derivatives were tested as sustaining agents: microcrystalline cellulose (MCC) and sodium carboxymethylcellulose (NaCMC). In-vitro dissolution studies were carried out in dissolution media of different pH. With MCC, the adsorption of acetaminophen on the surface or in the pores of the polymer does not allow a significant sustained release of the drug, which completely dissolves in 1 h. Conversely, the use of NaCMC retards the release of acetaminophen over a period of 6-8 h. The drug release depends on the plasticizer used and on the pH of the dissolution medium, and the mechanism consists essentially in the diffusion of the drug through the swollen polymeric matrix. The pH dependence observed can be correlated with a lower hydrophylicity of the polymer in acidic medium, which retards gel formation. [ABSTRACT FROM AUTHOR]

Microcrystalline cellulose (MCC), sodium carboxymethylcellulose (NaCMC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), hydroxypro pylcellulose (HPC), and ethylcellulose (EC) were used for the production of time-controlled acetaminophen delivery systems using a spray-drying technique. The influence of factors such as polymer concentration, inlet temperature, and drug/polymer ratio were investigated. The product yields were a function of the type and concentration of the polymer, with the highest values being reached from feeds containing 1% MCC and EC. Parameters of 1% polymer concentration and an inlet temperature of 140°C gave rise to optimal processing conditions. Using these parameters, the influence of some adjuncts, such as polyethylene glycol 6000 (PEG 6000), dibutyl sebacate (DBS), polyvinylpyrrolidone (PVP), and carboxylic acids such as citric acid (CA), phthalic acid (PA), succinic acid (SA), tartaric acid (TA), and oxalic acid (OA), on the spray-drying process was evaluated. Of the additives tested, PVP (with MCC), DBS (with EC), and PEG 6000 (with NaCMC) induced yield decreases from 70% to 49%, 66% to 39%, and 37% to 17%, respectively. As for carboxylic acids (with NaCMC), similar or better performances of 43%, 45%, 47%, and 49% were obtained with SA, OA, PA, and TA, respectively. Dissolution studies in pH 1 dilute HCl and pH 6.8 phosphate buffer dissolution media showed that formulations consisting of 1% polymer with a drug/polymer ratio of 1/1 exhibited the slowest drug release, with the spheroids coated with NaCMC and HEC showing the longest T50% values (with 45 and 53 min at pH 1 and 49 and 55 min at pH 6.8, respectively). Slightly better sustained drug release in pH 6.8 dissolution medium was reached, showing the following trend: HEC > NaCMC > MCC > EC > HPMC. Concerning the additives, the trends in dissolution T50% of drug revealed TA > SA > CA > OA > PVP > PA > DBS in acidic pH 1 dissolution medium and PVP > OA > TA >... [ABSTRACT FROM AUTHOR]

Objectif de l’étude Le traitement de première intention des carcinomes cutanés est la chirurgie. L’irradiation de contact, technique de radiothérapie délivrant des photons de basse énergie, est parfois une alternative de choix. C’est le cas pour les patients aux nombreuses maladies associées, ou pour les localisations difficiles comme les lésions péri-oculaires. Dans ces situations, la réunion de concertation pluridisciplinaire a tendance à orienter vers la contacthérapie. Nous rapportons ici l’expérience du centre Léonard-de-Vinci de Dechy. Matériel et méthode Entre janvier 2012 et juin 2017, 93 patients ont été pris en charge par contacthérapie pour des carcinomes cutanées périoculaires. L’irradiation était délivrée au moyen d’un appareil de type X-Strahl 100 utilisant des photons de basse énergie (de 50 kV). Le devenir des patients a été analysé par revue rétrospective des dossiers. Par ailleurs, les patients ont été contactés par téléphone pour rechercher la récidive et la toxicité tardive au moyen d’un questionnaire standardisé, et l’aspect esthétique a été noté de 0 à 10 par une autoévaluation. Résultats Dans la majorité des cas, il a été délivré une dose de 45 Gy en 15 fractions de 3 Gy, à raison de deux ou trois séances par semaine (79,3 % des cas). Le suivi médian était de 22 mois (extrêmes : 6–62 mois). Le taux de contrôle local à deux ans était de 96 % (intervalle de confiance à 95 % : 86–100). La toxicité tardive était de bas grade (0 % de grade ≥ 3) : il y avait 11,9 % de sécheresses oculaires (7,1 % de grade 1 ; 4,8 % de grade 2), ainsi que 11,9 % de larmoiements de grade 1. Enfin, l’autoévaluation esthétique retrouvait une note moyenne de 8,7/10, et 100 % des patients interrogés conseillaient ce traitement. Conclusion La radiothérapie de contact est un traitement de choix des carcinomes cutanés péri-oculaires. Elle permet d’obtenir un taux de contrôle local élevé, tout en maintenant des résultats fonctionnels et esthétiques excellents. Elle constitue une très bonne alternative thérapeutique en cas de contre-indication chirurgicale. [ABSTRACT FROM AUTHOR]

La tomothérapie, radiothérapie conformationnelle avec modulation d'intensité, permet une meilleure couverture des volumes cibles complexes pour l'irradiation adjuvante mammaire. L'objectif de cette étude était d'évaluer la toxicité aaiguë et tardive ainsi que la qualité de vie. Il s'agit d'une étude de soins courants, prospective, bicentrique, incluant les patientes prises charge par tomothérapie avec boost intégré pour un cancer du sein localisé. L'irradiation délivrait 50 Gy en 25 fractions de 2 Gy dans le sein ou la paroi, et les aires ganglionnaires, avec boost concomitant à la dose de 60 Gy (fractions de 2,4 Gy) dans le volume tumoral. En tout, 288 patientes ont été incluses de novembre 2014 à janvier 2018, dont 260 ont reçu une irradiation des aires ganglionnaires (soit 90,3 %). Le suivi médian était de 25 mois. Deux-cent-soixante-dix-huit patientes ont été atteintes d'une épithéliite aiguë (soit 96,5 %), dont 172 de grade 1 (soit 59,7 %), 102 de grade 2 (soit 35,4 %), et quatre de grade 3 (soit 1,4 %) ; 18 patientes ont été atteintes d'une œsophagite aiguë de grade 2 (soit 6,3 %) ; 86 patientes souffrant d'une toxicité cutanée chronique (soit 29,9 %), dont 82 cas de grade 1. Une fibrose mammaire et du lit opératoire de grade 2 ou plus a été retrouvée chez respectivement 18 patientes (soit 6,3 %) et 17 patientes (soit 10,1 %). En analyse multifactorielle, le tabagisme, la dose dans 98 % du volume de la peau susclaviculaire et l'absence de chimiothérapie étaient associés à la toxicité cutanée de grade 2 ou plus. L'aspect esthétique du sein à 1 an était jugé « bon ou excellent » dans 86,7 % des cas selon le médecin et 84,6 % selon les patientes. La qualité de vie représentée par un statut de santé globale, des échelles fonctionnelles et symptomatiques, s'améliorait pour la plupart des patientes au cours du temps, et ce de façon plus marquée pour celles ayant reçu une chimiothérapie. La tomothérapie du cancer du sein avec boost concomitant a une toxicité faible et donne de bons résultats esthétiques, cependant un suivi plus long est nécessaire. [ABSTRACT FROM AUTHOR]

Abstract: The increased need for predicting the properties of granular systems has become a growing challenge for the pharmaceutical industry. Experimental design has hastened developments in the field of pharmaceuticals and helped scientists to better understand the behavior of particles in the wet granulation process. In this research, the production of pellets containing binary mixtures of high-dose paracetamol (40, 60 and 80%) and microcrystalline cellulose (Microcel® MC 101) was evaluated. Three commercial grades of the drug at three concentrations each were used. Pellets were prepared by axial and radial extrusion systems and then spheronized. The formulation and process, as input variables, were analyzed using a response surface methodology (RSM). The responses considered as output variables were energy spent on the extrusion, particle size distribution of the granules and the parameters of the Weibull function, time (τ d) and shape (β), in terms of dissolution behavior. The results indicated that less energy is spent during the radial extrusion process for commercial-grade paracetamol with 80% of drug and fine particle size. Also, these conditions resulted in a higher percentage of the pellet being in the main size fraction (0.800–1.250mm) and a larger time required to dissolve 63.2% of the drug (τd). It was observed that the τ d value decreased with increasing particle size of the powder formulation. The β parameter was strongly influenced by the drug load and paracetamol grade for both extrusion procedures. The higher the content (percentage) and the smaller the particle size of the drug the higher the β parameter, indicating a parabolic shape changing to sigmoidal shape for the behavior of this parameter. These findings concerning formulations containing paracetamol can be extended to other drugs of equivalent particle size and water-solubility. The RSM tool was able to identify the manner and amplitude of the effects of the input variables on the output variables studied. [Copyright &y& Elsevier]