Concomitant chemotherapy (CT)–radiotherapy (RT) is a standard of care in locally advanced nasopharyngeal carcinoma (NPC) and a role for induction CT is not established.
Patients with locally advanced ...NPC, WHO type 2 or 3, were randomized to induction TPF plus concomitant cisplatin-RT or concomitant cisplatin-RT alone. The TPF regimen consisted of three cycles of Docetaxel 75mg/m2 day 1; cisplatin 75mg/m2 day 1; 5FU 750mg/m2/day days 1–5. RT consisted of 70Gy in 7weeks plus concomitant cisplatin 40mg/m2 weekly.
A total of 83 patients were included in the study. Demographics and tumour characteristics were well balanced between both arms. Most of the patients (95%) in the TPF arm received three cycles of induction CT. The rate of grade 3–4 toxicity and the compliance (NCI-CTCAE v3) during cisplatin-RT were not different between both arms. With a median follow-up of 43.1months, the 3-year PFS rate was 73.9% in the TPF arm versus 57.2% in the reference arm hazard ratio (HR)=0.44; 95% confidence interval (CI): 0.20–0.97, P=0.042. Similarly the 3years overall survival rate was 86.3% in the TPF arm versus 68.9% in the reference arm (HR=0.40; 95% CI: 0.15–1.04, P=0.05).
In conclusion, several important aspects can be emphasized: the compliance to induction TPF was good and TPF did not compromise the tolerance of the concomitant RT-cisplatin phase. The improved PFS and overall survival rates needs to be confirmed by further trials.
Les informations obtenues par les différentes modalités de la radiothérapie guidée par l’image (image-guided radiotherapy ou IGRT), nous permettent de passer d’un repositionnement orienté sur le ...patient, à un repositionnement centré sur le volume cible. Cette évolution entraîne ainsi une modification des pratiques de contrôle de positionnement. Afin de maîtriser les erreurs de positionnement systématiques, un contrôle lors des trois à cinq premières séances est nécessaire. Les erreurs de repositionnement aléatoires, comme les mouvements de volume cible ne peuvent être maîtrisés que par la réalisation d’une imagerie quotidienne. Enfin, les modalités de radiothérapie guidée par l’image permettent d’évaluer les modifications anatomiques survenant en cours de traitement et ouvrent le champ de la radiothérapie adaptative.
Information obtained by different methods of image-guided radiotherapy now allows us to reposition the target volume. This evolution causes a change in practice and positioning control. In order to control positioning errors, a systematic control during the first three to five sessions is required. Random repositioning errors and clinical target volume motions can be mastered only by performing a daily imaging. Finally, image-guided radiotherapy allows assessing anatomical changes occurring during treatment, and opens the field of adaptive radiotherapy.
To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab–RT in patients with locally advanced-squamous cell carcinoma of head ...and neck (LA-SCCHN).
Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab–RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab–RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20.
Between May 2016 and October 2017, 133 patients were randomized to cetuximab–RT (n = 66) and pembrolizumab–RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab–RT and 60% with pembrolizumab–RT odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab–RT arm than in the cetuximab–RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash.
Compared with the SOC cetuximab–RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.
•This is the first randomized trial testing pembrolizumab–RT versus cetuximab–RT in patients with LA-SCCHN.•No difference of LRC at 15 months between concurrent pembrolizumab–RT and cetuximab–RT.•No difference in overall survival or progression-free survival between the two arms at 2-year follow-up.•Significantly more grade ≥3 adverse events with cetuximab–RT, essentially due to skin and mucosal reactions.
Triple-GEM detectors with pad readout have been employed to equip the innermost region (R1) of the first station (M1) within the Muon system of the LHCb experiment. The GEM detectors have been ...operated with an Ar/CO2/CF4 = 45/15/40 gas mixture at a gas gain of about 4000 with an average particle flux of about 250 kHz/cm2. Throughout RUN1 and RUN2, spanning approximately 440 days of colliding beams, the GEM detectors accumulated a charge of up to 0.5 C/cm2. This paper presents a comparative analysis between a global irradiation test of GEM detectors at the Calliope facility (ENEA-Casaccia, 1.25 MeV γ ray flux from a 60Co source) and the GEMs operated at LHCb, focusing on the impacts of a CF4-based gas mixture. In both instances, the detectors were opened and the GEM foils were examined by the EN-MME-MM CERN group with a Field Emission Gun Scanning Electron Microscope (FEG-SEM) for a magnified image analysis and an X-Max Energy Dispersive X-ray Spectroscopy (EDS) for the chemical one.
Background
The recent introduction of microarrays for genetic analyses has allowed higher etiological diagnostic rates in patient with intellectual disability (ID), autism spectrum disorders (ASD), ...epilepsy and multiple congenital anomalies (MCA), because of its resolution. This approach still results of high complexity and some limitations have been reported. In fact, it discloses several variants of unknown significance (VOUS) or incidental findings. In all cases, a massive amount of data is generated, because of this, the analysis and the interpretation is very difficult and often without a definitive conclusion.
Method
We analysed an Italian cohort of 343 patients with ID, MCA and ASD by array‐comparative genomic hybridization. The purpose of this work was to consider the proportion of the chromosomal abnormalities in such cohort and to assess the distribution of the different type of the chromosomal abnormalities concerning their pathogenic significance, their origin and their correlation to these clinical phenotypes.
Results
Array‐comparative genomic hybridization analysis revealed 76 positive results. Abnormalities were detected in 27.8% of patients with ID, 11.1% with ASD, 10.7% with epilepsy and 19.4% with multiple congenital anomalies. The anomalies were classified in three major groups: group 1 (27 patients) with pathogenic alterations (P group); group 2 (34 patients) with VOUS potentially pathogenic (PP group); and group 3 (13 patients) with VOUS potentially benign (PB group). As expected, comparing the diagnostic groups, we observed a greater number of deletions in the P group and that all the abnormalities of the PB group were inherited.
Conclusions
Our retrospective study resulted in confirming the high detection rate of microarrays. CNV classification remains a complex procedure. The difficulty in CNV classification points out the importance of the patient selection, helping the interpretation of the molecular cytogenetic results.
Simulation of the dielectric charging-up effect in a GEM detector Alfonsi, M.; Croci, G.; Duarte Pinto, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2012, Volume:
671
Journal Article
Peer reviewed
Open access
The charging up effect is well-known in detectors containing dielectric materials and it is due to electrons and ions liberated in an avalanche and collected on the dielectric surfaces. In particular ...in Gas Electron Multiplier (GEM) based detectors, charges can be captured by the Kapton that separates top and bottom electrodes. The collection of a substantial number of charges on the dielectric surfaces induces a modification of the field inside the GEM holes that implies important consequences on some fundamental parameters such as the electron transparency and the effective gain. The correct simulation of this effect opens new ways to the detailed study of the processes that happens in a GEM-based detector and gives the possibility to optimise the GEM geometry in order to avoid it. This paper compares results of the measurements and the simulations, with and without the introduction of the charging-up effect, of the GEM electron transparency in the case of a single GEM detector. The introduction of the charging up effect in the simulation resulted to be crucial in order to get the proper agreement with the measurements. The measurements and simulations of the GEM effective gain will be the subject of a future work.
Neutron GEM-based detectors represent a new frontier of diagnostic devices in neutron-linked physics applications such as detectors for fusion experiments (Croci et al., 2012 1) and spallation ...sources (Murtas et al., 2012 2). Besides, detectors installed in HEP experiments (like LHC at CERN) are dip in a high flux neutron field. For example, the TOTEM T2 GEM telescope (Bagliesi et al., 2010 3) at LHC is currently installed very close to the beam pipe where a high intensity (>104ncm−2s−1) neutron background is present. In order to assess the capability (particularly related to discharge probability) of working in intense neutrons environment, a 10×10cm2 Triple GEM detector has been tested using a high flux (105ncm−2s−1) neutron beam. The neutron-induced discharge probability PDisch was measured to be 1.37×10−7 at an effective gain G=5×104. In addition, the different types of neutron interactions within the detector were fully explained through a GEANT4 simulation.
La radiothérapie conformationnelle avec modulation d'intensité (RCMI) est une nouvelle technique de radiothérapie de haute précision qui doit permettre de limiter la toxicité de la radiothérapie, ...sans compromettre la probabilité de contrôle tumoral. Il s'agit d'une technique plus complexe et plus coûteuse que la radiothérapie classique dont la mise en œuvre nécessite une assurance de qualité renforcée. Les premiers résultats prometteurs obtenus pour les carcinomes des voies aérodigestives supérieures doivent être confirmés par des études cliniques complémentaires, si possible randomisées, pour préciser quelles sont les indications de cette technique dans les carcinomes des voies aérodigestives supérieures et si les bénéfices observés jusqu'à présent sont transposables à l'ensemble des carcinomes des voies aérodigestives supérieures et, en particulier, aux présentations cliniques les plus fréquentes qui sont localement évoluées.
Intensity-modulated radiotherapy (IMRT) is a new high precision radiotherapy technique, allowing to protect some normal tissues without compromising the tumour cure probability. This is a more complex and more costly technique, compared to conventional radiotherapy, which needs increased quality assurance programs. The early results obtained in head-and-neck carcinomas have been very promising but would need to be confirmed in randomised trials to determine whether these results can be transposed to the majority of these cancers and especially to locally advanced cases, which are the most frequently occurring forms of these cancers.
Round spermatids contain high levels of extremely varied mRNAs that are synthesized either throughout early spermatogenesis or during spermiogenesis from the haploid genome. Concomitantly, with major ...changes in the chromatin organization, arrest of transcription occurs at midspermiogenesis. However, previous investigations using RT–PCR have revealed the persistence of numerous and different transcripts in ejaculated spermatozoa. In the present study, a step-by-step analysis by means of macroarray hybridization, RT–PCR and in situ hybridization was performed to identify more accurately the different mRNA species found in the human ejaculated spermatozoa. The data showed an extended pattern of various transcripts encoding a diverse range of proteins involved in signal transduction and cell proliferation. For the first time, they demonstrated that mRNAs coding for the transcription factors NFκB, HOX2A, ICSBP, protein kinase JNK2, growth factor HBEGF and receptors RXRβ and ErbB3 accumulate within the sperm nucleus. The origin and fate of the sperm transcripts remain subject to discussion.
PDF
