First-Line LV5FU2 with or without Aflibercept in Patients with Non-Resectable Metastatic Colorectal Cancer: A Randomized Phase II Trial (PRODIGE 25-FFCD-FOLFA).

Fluropyrimidine monotherapy is an option for some patients with inoperable metastatic colorectal cancer. Unlike bevacizumab, the addition of aflibercept, an antibody acting as an anti-angiogenic agent, has never been evaluated in this context. The aim of the study was to determine whether aflibercept could increase the efficacy of fluoropyrimidine monotherapy without increasing toxicity. This multicenter phase II non-comparative trial evaluated the addition of aflibercept to infusional 5-fluorouracil/folinic acid (LV5FU2 regimen) as first-line treatment in patients unfit to receive doublet cytotoxic chemotherapy. The primary endpoint was 6-month progression-free survival (PFS). The clinical hypotheses expected a PFS rate at 6 months of over 40% (60% expected). A total of 117 patients, with a median age of 81 years, were included: 59 in arm A (LV5FU2-aflibercept) and 58 in arm B (LV5FU2 alone). Six-month PFS was 54.7% in both arms (90% CI 42.5-66.5 in both). Median overall survival was 21.8 months (arm A) and 25.1 months (arm B). Overall toxicity was more common in arm A: grade ≥ 3 toxicity in 82% versus 58.2%. Given the 6-month PFS, the study can be considered positive. However, the toxicity of aflibercept in this population was high, and continuation of the trial into phase III is not envisaged.

Design and modeling of a Laue lens for radiation therapy with hard x-ray photons.

We have designed and modeled a novel optical system composed of a Laue lens coupled to an x-ray tube that produces a focused beam in an energy range near 100 keV (λ= 12.4 picometer). One application of this system is radiation therapy where it could enable treatment units that are considerably simpler and lower in cost than present technologies relying on linear accelerators. The Laue lens is made of Silicon Laue components which exploit the silicon pore optics technology. The lens concentrates photons to a small region thus allowing high dose rates at the focal area with very much lower dose rates at the skin and superficial regions. Monte Carlo simulations with Geant4 indicate a dose deposition rate of 0.2 Gy min-1in a cylindrical volume of 0.7 mm diameter and 10 mm length, and a dose ratio of 72 at the surface (skin) compared to the focus placed 10 cm within a water phantom. Work is ongoing to newer generation crystal technologies to increase dose rate.

[Can trees and forests help in improving environmental noise quality?] / Les arbres et les forêts peuvent-ils contribuer à l'amélioration de l'environnement sonore ?

In this article, we focus on ground transportation noise abatement and more precisely road traffic noise control. From literature as well as our own experience in this field we aim at determining in which planting schemes are trees or forest strips beneficial to environmental noise abatement, for which expected noise attenuation and with which good practices.We start by a brief point on French regulation on road noise management and we present a synthetic review of main attenuation processes observed when sounds propagates through areas with trees: ground, diffusion and refraction effects. Then we consider some typical landscape configurations studied in the scientific literature and we provide with expected acoustic impact: a forest strip along a road infrastructure, a row of trees along a noise protection and trees in the city. We finally give a set of recommendations of correct use of trees and forest strips as an element to the improvement of outdoor sound environment. Our advice is to plant broadleaved evergreens or a mixture of broadleaved evergreens and coniferous, with a minimum density of 0.25 tree/m2. We also advise to cultivate the ground before trees planting and to use well-rotted organic matter. On the other hand we do not recommend planting trees at the top of earth berms.

Extended hard-X-ray emission in the inner few parsecs of the Galaxy.

The Galactic Centre hosts a puzzling stellar population in its inner few parsecs, with a high abundance of surprisingly young, relatively massive stars bound within the deep potential well of the central supermassive black hole, Sagittarius A* (ref. 1). Previous studies suggest that the population of objects emitting soft X-rays (less than 10 kiloelectronvolts) within the surrounding hundreds of parsecs, as well as the population responsible for unresolved X-ray emission extending along the Galactic plane, is dominated by accreting white dwarf systems. Observations of diffuse hard-X-ray (more than 10 kiloelectronvolts) emission in the inner 10 parsecs, however, have been hampered by the limited spatial resolution of previous instruments. Here we report the presence of a distinct hard-X-ray component within the central 4 × 8 parsecs, as revealed by subarcminute-resolution images in the 20-40 kiloelectronvolt range. This emission is more sharply peaked towards the Galactic Centre than is the surface brightness of the soft-X-ray population. This could indicate a significantly more massive population of accreting white dwarfs, large populations of low-mass X-ray binaries or millisecond pulsars, or particle outflows interacting with the surrounding radiation field, dense molecular material or magnetic fields. However, all these interpretations pose significant challenges to our understanding of stellar evolution, binary formation, and cosmic-ray production in the Galactic Centre.

Loss of Bcl-2 expression in colon cancer: a prognostic factor for recurrence in stage II colon cancer.

AIMS: To evaluate the prognostic value of immunohistochemical expression of Bcl-2 in colon cancers. PATIENTS AND METHODS: Two hundred and twenty-six resected and paraffin-embedded colon carcinomas were analysed by immunostaining using monoclonal antibodies for Bcl-2. We evaluated whether the Bcl-2 staining patterns, semi-quantitatively assessed, could be correlated with the pTNM stage, size and tumour circumference, differentiation, appearance, vascular invasion, perineural invasion, colloid component, margins, involvement of adjacent structures, stromal appearance, flow cytometry and the S-phase. RESULTS: Eighty patients (36%) were considered Bcl-2 positive. The extent of Bcl-2 expression by tumour cells decreased significantly with respect to increasing tumour size (P=0.042), the extension of parietal invasion pT (P=0.007), the invasive nature of the tumour (P=0.024), and extent of the circumference (P=0.024). In a multivariate analysis, Bcl-2 expression does not appear as an independent prognosis factor in the overall population as in the 166 patients with optimal resection. Of the 59 stage II patients, using univariate analysis, Bcl-2 appears to be predictive of relapse-free survival (P=0.025) but not of overall survival (P=0.09). CONCLUSION: The loss of Bcl-2 expression appears to be correlated with increase in number of relapses in the stage II colon cancers and could be a potential useful additional histo-prognostic marker in therapy decision making. Bcl-2 immunodetection seems to be associated with slower local tumour growth.