Cancers du sein : comment associer l'hormonothérapie et la radiothérapie en situation adjuvante [How to combine hormonotherapy and radiation treatment in adjuvant breast cancer?]

Combined radiation and hormone therapies have become common clinical practice in recent years for locally-advanced prostate cancers. The use of such concomitant therapy in the treatment of breast disease has been infrequently reported in the literature, but seems justified given the common hormonal dependence of breast cancer and the potential synergistic effect of these two treatment modalities. As adjuvant therapy, two strategies are used in daily clinical practice: upfront aromatase inhibitors or sequentially after a variable delay of tamoxifen. These molecules may, thus, interact with radiotherapy. Retrospectives studies recently published did not show any differences in terms of locoregional recurrences between concurrent or sequential radiohormonotherapy. Lung and skin fibroses due to concurrent treatment are still under debate. Nevertheless, late side effects appeared to be increased by such a treatment, particularly in hypersensitive patients identified at risk by the lymphocyte predictive test. Concurrent radiohormonotherapy should, thus, be delivered cautiously at least for these patients. This article details the potent advantages and risks of concurrent use of adjuvant hormonotherapy and radiotherapy in localized breast cancers.

Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy.

Ultrafractionation of radiation therapy is a novel regimen consisting of irradiating tumors several times daily, delivering low doses (<0.75 Gy) at which hyperradiosensitivity occurs. We recently demonstrated the high efficiency of ultrafractionated radiotherapy (RT) on glioma xenografts and report here on a phase II clinical trial to determine the safety, tolerability, and efficacy of an ultrafractionation regimen in patients with newly and inoperable glioblastoma (GBM). Thirty-one patients with histologically proven, newly diagnosed, and unresectable supratentorial GBM (WHO grade IV) were enrolled. Three daily doses of 0.75 Gy were delivered at least 4 hours apart, 5 days per week over 6-7 consecutive weeks (90 fractions for a total of 67.5 Gy). Conformal irradiation included the tumor bulk with a margin of 2.5 cm. The primary end points were safety, toxicity, and tolerability, and the secondary end points were overall survival (OS) and progression-free survival (PFS). Multivariate analysis was used to compare the OS and PFS with the EORTC-NCIC trial 26981-22981/CE.3 of RT alone vs radiation therapy and temozolomide (TMZ). The ultrafractionation radiation regimen was safe and well tolerated. No acute Grade III and/or IV CNS toxicity was observed. Median PFS and OS from initial diagnosis were 5.1 and 9.5 months, respectively. When comparing with the EORTC/NCIC trial, in both PFS and OS multivariate analysis, ultrafractionation showed superiority over RT alone, but not over RT and TMZ. The ultrafractionation regimen is safe and may prolong the survival of patients with GBM. Further investigation is warranted and a trial associating ultra-fractionation and TMZ is ongoing.

The radiation of the clownfishes has two geographical replicates

AimThe study of adaptive radiations provides an evolutionary perspective on the interactions between organisms and their environment, and is necessary to understand global biodiversity. Adaptive radiations can sometimes be replicated over several disjunct geographical entities, but most examples are found on island or in lakes. Here, we investigated the biogeographical history of the clownfishes, a clade of coral reef fish with ranges that now span most of the Indo-Pacific Ocean, in order to explore the geographical structure of an unusual adaptive radiation. LocationIndian Ocean, Indo-Australian Archipelago (IAA) and Central Pacific Ocean. MethodsWe generated DNA sequence data comprising seven nuclear markers for 27 of the 30 clownfish species. We then inferred a Bayesian phylogeny and reconstructed the biogeographical history of the group using three different methods. Finally, we applied a biogeographical model of diversification to assess whether diversification patterns differ between the Indian and Pacific Oceans. ResultsThe phylogenetic tree is highly supported and allows reconstruction of the biogeographical history of the clade. While most species arose in the IAA, one clade colonized the eastern shores of Africa and diversified there. We found that the diversification rate of clownfishes does not differ between the main radiation and the African clade. Main conclusionsThe clownfishes first appeared and diversified in the IAA. Following a colonization event, a geographically independent radiation occurred in the Indian Ocean off East Africa. This rare example of replicated adaptive radiation in the marine realm provides intriguing possibilities for further research on ecological speciation in the sea.

Changes in patterns of practice for prostate cancer radiotherapy in Italy 1995-2003. A survey of the Prostate Cancer Study Group of the Italian Radiation Oncology Society.

Aims and background. In 2002, a survey including 1759 patients treated from 1980 to 1998 established a "benchmark" Italian data source for prostate cancer radiotherapy. This report updates the previous one. Methods. Data on clinical management and outcomes of 3001 patients treated in 15 centers from 1999 through 2003 were analyzed and compared with those of the previous survey. Results. Significant differences in clinical management (-10% had abdominal ma-gnetic resonance imaging; +26% received ≥70 Gy, +48% conformal radiotherapy, -20% pelvic radiotherapy) and in G3-4 toxicity rates (-3.8%) were recorded. Actuarial 5-year overall, disease-specific, clinical relapse-free, and biochemical relapse-free survival rates were 88%, 96%, 96% and 88%, respectively. At multivariate analysis, D'Amico risk categories significantly impacted on all the outcomes; higher radiotherapy doses were significantly related with better overall survival rates, and a similar trend was evident for disease-specific and biochemical relapse-free survival; cumulative probability of 5-year late G1-4 toxicity was 24.8% and was significantly related to higher radiotherapy doses (P <0.001). Conclusions. The changing patterns of practice described seem related to an improvement in efficacy and safety of radiotherapy for prostate cancer. However, the impact of the new radiotherapy techniques should be prospectively evaluated.

Predictions from information-theoretical models of nonequilibrium radiation

The radiation distribution function used by Domínguez and Jou [Phys. Rev. E 51, 158 (1995)] has been recently modified by Domínguez-Cascante and Faraudo [Phys. Rev. E 54, 6933 (1996)]. However, in these studies neither distribution was written in terms of directly measurable quantities. Here a solution to this problem is presented, and we also propose an experiment that may make it possible to determine the distribution function of nonequilibrium radiation experimentally. The results derived do not depend on a specific distribution function for the matter content of the system

Temporal variability and trends of the downward solar radiation over Europe during the 20th century, with regional focus in the dimming/brightening phenomena on the Iberian Peninsula

Proyecto de investigación elaborado a partir de una estancia en el Institute for Atmospheric and Climate Science, a Alemanya, entre 2010 y 2012. La radiación solar que alcanza la superficie terrestre es un factor clave entre los procesos que controlan el clima de la Tierra, dado el papel que desempeñan en el balance energético y el ciclo hidrológico. Establecer su contribución al cambio climático reciente supone una gran dificultad debido a la complejidad de los procesos implicados, la gran cantidad de información requerida, y la incertidumbre de las bases de datos disponibles en la actualidad. Así, el objetivo principal del proyecto ha consistido en generar una base de datos de insolación incluyendo las series más largas (desde finales del siglo XIX) disponibles en toda Europa. Esta base de datos complementa para nuestro continente el Global Energy Balance Archive (GEBA) que mantiene y gestiona el grupo que ha acogido al receptor de la ayuda postdoctoral, y permite extender espacial (especialmente en países del sur de Europa) y temporalmente las series climáticas disponibles de mediciones de irradiancia solar. Como la insolación es un proxy de la irradiancia solar, el proyecto actual también ha tratado de calibrar de forma exhaustiva ambas variables, a fin de generar una nueva base de datos reconstruida de esta segunda variable que esté disponible desde finales del siglo XIX en Europa. Un segundo objetivo del proyecto ha consistido en continuar trabajando a escala de mayor detalle sobre la Península Ibérica, con el fin de proporcionar una mejor comprensión del fenómeno del “global dimming/brightening” y su impacto en el ciclo hidrológico y balance energético. Finalmente, un tercer objetivo del presente proyecto postdoctoral ha consistido en continuar estudiando los posibles ciclos semanales a gran escala de diferentes variables climáticas, línea de investigación de interés para la detección de posibles efectos de los aerosoles antrópicos en el clima a escalas temporales breves, y consecuentemente estrechamente vinculado al fenómeno del “global dimming/brightening”.

FY 2004 School District Funding Sources and Amounts, 2003

School district funding sources and amounts

Auditory-visual multisensory interactions in humans: timing, topography, directionality, and sources.

Current models of brain organization include multisensory interactions at early processing stages and within low-level, including primary, cortices. Embracing this model with regard to auditory-visual (AV) interactions in humans remains problematic. Controversy surrounds the application of an additive model to the analysis of event-related potentials (ERPs), and conventional ERP analysis methods have yielded discordant latencies of effects and permitted limited neurophysiologic interpretability. While hemodynamic imaging and transcranial magnetic stimulation studies provide general support for the above model, the precise timing, superadditive/subadditive directionality, topographic stability, and sources remain unresolved. We recorded ERPs in humans to attended, but task-irrelevant stimuli that did not require an overt motor response, thereby circumventing paradigmatic caveats. We applied novel ERP signal analysis methods to provide details concerning the likely bases of AV interactions. First, nonlinear interactions occur at 60-95 ms after stimulus and are the consequence of topographic, rather than pure strength, modulations in the ERP. AV stimuli engage distinct configurations of intracranial generators, rather than simply modulating the amplitude of unisensory responses. Second, source estimations (and statistical analyses thereof) identified primary visual, primary auditory, and posterior superior temporal regions as mediating these effects. Finally, scalar values of current densities in all of these regions exhibited functionally coupled, subadditive nonlinear effects, a pattern increasingly consistent with the mounting evidence in nonhuman primates. In these ways, we demonstrate how neurophysiologic bases of multisensory interactions can be noninvasively identified in humans, allowing for a synthesis across imaging methods on the one hand and species on the other.

Status of eye lens radiation dose monitoring in European hospitals.

A questionnaire was developed by the members of WG12 of EURADOS in order to establish an overview of the current status of eye lens radiation dose monitoring in hospitals. The questionnaire was sent to medical physicists and radiation protection officers in hospitals across Europe. Specific topics were addressed in the questionnaire such as: knowledge of the proposed eye lens dose limit; monitoring and dosimetry issues; training and radiation protection measures. The results of the survey highlighted that the new eye lens dose limit can be exceeded in interventional radiology procedures and that eye lens protection is crucial. Personnel should be properly trained in how to use protective equipment in order to keep eye lens doses as low as reasonably achievable. Finally, the results also highlighted the need to improve the design of eye dosemeters in order to ensure satisfactory use by workers.

Distortion control for delay-sensitive sources

We investigate the problem of finding minimum-distortion policies for streaming delay-sensitive but distortion-tolerant data. We consider cross-layer approaches which exploit the coupling between presentation and transport layers. We make the natural assumption that the distortion function is convex and decreasing. We focus on a single source-destination pair and analytically find the optimum transmission policy when the transmission is done over an error-free channel. This optimum policy turns out to be independent of the exact form of the convex and decreasing distortion function. Then, for a packet-erasure channel, we analytically find the optimum open-loop transmission policy, which is also independent of the form of the convex distortion function. We then find computationally efficient closed-loop heuristic policies and show, through numerical evaluation, that they outperform the open-loop policy and have near optimal performance.

Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer.

Although non-melanoma skin cancer (NMSC) is the most common human cancer and its incidence continues to rise worldwide, the mechanisms underlying its development remain incompletely understood. Here, we unveil a cascade of events involving peroxisome proliferator-activated receptor (PPAR) β/δ and the oncogene Src, which promotes the development of ultraviolet (UV)-induced skin cancer in mice. UV-induced PPARβ/δ activity, which directly stimulated Src expression, increased Src kinase activity and enhanced the EGFR/Erk1/2 signalling pathway, resulting in increased epithelial-to-mesenchymal transition (EMT) marker expression. Consistent with these observations, PPARβ/δ-null mice developed fewer and smaller skin tumours, and a PPARβ/δ antagonist prevented UV-dependent Src stimulation. Furthermore, the expression of PPARβ/δ positively correlated with the expression of SRC and EMT markers in human skin squamous cell carcinoma (SCC), and critically, linear models applied to several human epithelial cancers revealed an interaction between PPARβ/δ and SRC and TGFβ1 transcriptional levels. Taken together, these observations motivate the future evaluation of PPARβ/δ modulators to attenuate the development of several epithelial cancers.