Carotid Dose Spring in Definitive Irradiation of T1N0 Squamous Cell Laryngeal Carcinoma Using Helical Tomotherapy

Purpose/Objective(s): To implement a carotid dose sparing protocol using helical Tomotherapy in T1N0 squamous cell laryngeal carcinoma.Materials/Methods: Between July and August 2010, 7 men with stage T1N0 laryngeal carcinoma were included in this study. Age ranged from 47 - 74 years. Staging included endoscopic examination, CT-scan and MRI when indicated. Planned irradiation dose was 70 Gy in 35 fractions over 7 weeks. A simple treatment planning algorithm for carotid sparing was used: maximum point dose to the carotids 35 Gy, to the spinal cord 30 Gy, and 100% PTV volume to be covered with 95% of the prescribed dose. Carotid volume of interest extended to 1 cm above and below of the PTV. Doses to the carotid arteries, to the critical organs, and to the planned target volume (PTV) with our standard laryngeal irradiation protocol was compared. Daily megavoltage scans were obtained before each fraction. When necessary, the Planned Adaptive software (TomoTherapy Inc., Madison, WI) was used to evaluatethe need for a re-planning, which has never been indicated. Dose data were extracted using the VelocityAI software (Atlanta, GA), and data normalization and dose-volume histogram (DVH) interpolation were realized using the Igor Pro software (Portland, OR).Results:A significant (p\0.05) carotid dose sparing compared to our standard protocol with an average maximum point dose of 38.3 Gy (standard deviation [SD] 4.05 Gy), average mean dose of 18.59 Gy (SD 0.83 Gy) was achieved. In all patients, 95% of the carotid volume received less than 28.4 Gy (SD 0.98 Gy). The average maximum point dose to the spinal cord was 25.8 Gy (SD 3.24 Gy). PTV was fully covered with more than 95% of the prescribed dose for all patients with an average maximum point dose of 74.1 Gy and the absolute maximum dose in a single patient of 75.2 Gy. To date, the clinical outcomes have been excellent. Three patients (42%) developed stage 1 mucositis that was conservatively managed, and all the patients presented a mild to moderate dysphonia. All adverse effects resolved spontaneously in the month following the end of treatment. Early local control rate is 100% considering a 4 - 5 months post treatment follow-up.Conclusions: Helical Tomotherapy allows a clinically significant decrease of carotid irradiation dose compared to standard irradiation protocols with an acceptable spinal cord dose tradeoff. Moreover, this technique allows the PTV to be homogenously covered with a curative irradiation dose. Daily control imaging brings added security margins especially when working with high dose gradients. Further investigations and follow-up are underway to better evaluate the late clinical outcomes especially the local control rate, late laryngeal and vascular toxicity, and expected potential impact on cerebrovascular events.

An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells.

Arteriovenous-lymphatic endothelial cell fates are specified by the master regulators, namely, Notch, COUP-TFII, and Prox1. Whereas Notch is expressed in the arteries and COUP-TFII in the veins, the lymphatics express all 3 cell fate regulators. Previous studies show that lymphatic endothelial cell (LEC) fate is highly plastic and reversible, raising a new concept that all 3 endothelial cell fates may co-reside in LECs and a subtle alteration can result in a reprogramming of LEC fate. We provide a molecular basis verifying this concept by identifying a cross-control mechanism among these cell fate regulators. We found that Notch signal down-regulates Prox1 and COUP-TFII through Hey1 and Hey2 and that activated Notch receptor suppresses the lymphatic phenotypes and induces the arterial cell fate. On the contrary, Prox1 and COUP-TFII attenuate vascular endothelial growth factor signaling, known to induce Notch, by repressing vascular endothelial growth factor receptor-2 and neuropilin-1. We show that previously reported podoplanin-based LEC heterogeneity is associated with differential expression of Notch1 in human cutaneous lymphatics. We propose that the expression of the 3 cell fate regulators is controlled by an exquisite feedback mechanism working in LECs and that LEC fate is a consequence of the Prox1-directed lymphatic equilibrium among the cell fate regulators.

Right coronary MR angiography at 7 T: a direct quantitative and qualitative comparison with 3 T in young healthy volunteers.

PURPOSE: To objectively compare quantitative parameters related to image quality attained at coronary magnetic resonance (MR) angiography of the right coronary artery (RCA) performed at 7 T and 3 T. MATERIALS AND METHODS: Institutional review board approval was obtained, and volunteers provided signed informed consent. Ten healthy adult volunteers (mean age ± standard deviation, 25 years ± 4; seven men, three women) underwent navigator-gated three-dimensional MR angiography of the RCA at 7 T and 3 T. For 7 T, a custom-built quadrature radiofrequency transmit-receive surface coil was used. At 3 T, a commercial body radiofrequency transmit coil and a cardiac coil array for signal reception were used. Segmented k-space gradient-echo imaging with spectrally selective adiabatic fat suppression was performed, and imaging parameters were similar at both field strengths. Contrast-to-noise ratio between blood and epicardial fat; signal-to-noise ratio of the blood pool; RCA vessel sharpness, diameter, and length; and navigator efficiency were quantified at both field strengths and compared by using a Mann-Whitney U test. RESULTS: The contrast-to-noise ratio between blood and epicardial fat was significantly improved at 7 T when compared with that at 3 T (87 ± 34 versus 52 ± 13; P = .01). Signal-to-noise ratio of the blood pool was increased at 7 T (109 ± 47 versus 67 ± 19; P = .02). Vessel sharpness obtained at 7 T was also higher (58% ± 9 versus 50% ± 5; P = .04). At the same time, RCA vessel diameter and length and navigator efficiency showed no significant field strength-dependent difference. CONCLUSION: In our quantitative and qualitative study comparing in vivo human imaging of the RCA at 7 T and 3 T in young healthy volunteers, parameters related to image quality attained at 7 T equal or surpass those from 3 T.

La implicació de les famílies immigrades en els processos educatius dels seus fills/es: estratègies davant l'èxit i el fracàs escolar

En el present projecte hem analitzat els determinants de les trajectòries educatives dels i les adolescents d'origen immigrant, centrant I'atenció en el paper de les seves famílies davant de I ‘èxit o fracàs escolar del seu fillla. Amb aquest objectiu, I'estudi combina tècniques quantitatives i qualitatives. Per una banda hem analitzat les dades longitudinals del Panel de Famílies i lnfancia, que ens permeten fer un seguiment de les trajectòries educatives i personals de 248 alumnes d'origen immigrant que al 2006 estudiaven I'ESO al llarg de la seva adolescència, i identificar els factors socials responsables de la seva diversificació. Els resultats indiquen que malgrat presentar actituds bastant favorables als estudis i I'assoliment educatiu, concentren diverses situacions de vulnerabilitat a la llar (dificultats socioeconòmiques, estructures familiars atípiques, i erosió de capital social), que incideixen negativament sobre els seus rendiments acadèmics. Per altra, hem realitzat 59 entrevistes semi-estructurades per a complementar i facilitar la interpretació dels resultats obtinguts a la recerca quantitativa i copsar les narratives dels propis protagonistes. Aquestes entrevistes s'han realitzat a: una submostra de les famílies d'aquests alumnes, seleccionades en funció de perfils d’èxit o fracàs educatiu de la trajectòria del menor (46), una submostra d'estudiants resilients (a), i una sèrie d'agents educatius i socials, que inclou membres d'equips directius de centres escolars, AMPA i entitats dedicades a I'atenció a la infància i les famílies (5). El projecte que presentem té una clara vocació de servei públic. L'objectiu és incrementar el coneixement de factors "extraescolars" que poden condicionar I ‘èxit escolar dels estudiants d'origen immigrant. Aquest coneixement constitueix la base per al disseny i orientació de programes d'acompanyament a les famílies dels infants en situació de risc. La nostra voluntat (que reflecteix el principal objectiu de I'lnstitut d’infància i Món Urbà, instituci6 que impulsa el projecte) és contribuir a la transferència de coneixement que pugui ser d'utilitat pels agents que treballen directament sobre les qüestions que estudiem.