A randomized phase II study comparing sequential versus simultaneous chemo-radiotherapy in patients with unresectable locally advanced squamous cell cancer of the head and neck

Background: Single-modality radiotherapy is still considered standard treatment for patients with locally advanced unresectable cancer of the head and neck. As treatment outcome is poor, attempts to integrate chemotherapy into the overall management of these patients are ongoing. Patients and methods: A randomized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program. Between February 1986 and February 1991, 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS, T and N class and primary site and then randomized to receive either three courses of neoadjuvant chemotherapy with cisplatin (100 mg/m2 i.v. d 1) and 5-fluorouracil 1000 mg/m2/days 1-5 by continuous i.v. infusion every 3 weeks prior to definitive conventional radiotherapy of 65-70 Gy (sequential treatment), or cisplatin 100 mg/m2 on days 1, 22, 43 given simultaneously for the duration of the same conventional radiotherapy (simultaneous treatment). Results: At the end of the entire treatment 18 complete responses (47%) in the sequential-treatment arm and 18 (41%) in the simultaneous treatment arm were obtained. No statistically significant differences in the 5-yr progression-free survival, in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed. Leukopenia was more frequent in the simultaneous than in the sequential arm (p = 0.03), whereas alopecia (p = 0.008) and phlebitis (p < 0.0001) were more frequent in the sequential-treatment arm. A better compliance was associated with the concomitant treatment, with 87% of the patients completing the entire radiotherapy program versus 63% of those in the sequential arm (p = 0.01). Conclusions: In the present study, the two treatment arms showed similar activity (complete response, progression-free and overall survival rates). Compliance to treatment was better in the concomitant arm. These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck. Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone

Acid and neutral sphingomyelinase behavior in radiation-induced liver pyroptosis and in the protective/preventive role of rMnSOD

Sphingomyelins (SMs) are a class of relevant bioactive molecules that act as key modulators of different cellular processes, such as growth arrest, exosome formation, and the inflammatory response influenced by many environmental conditions, leading to pyroptosis, a form of programmed cell death due to Caspase-1 involvement. To study liver pyroptosis and hepatic SM metabolism via both lysosomal acid SMase (aSMase) and endoplasmic reticulum/nucleus neutral SMase (nSMase) during the exposure of mice to radiation and to ascertain if this process can be modulated by protective molecules, we used an experimental design (previously used by us) to evaluate the effects of both ionizing radiation and a specific protective molecule (rMnSOD) in the brain in collaboration with the Joint Institute for Nuclear Research, Dubna (Russia). As shown by the Caspase-1 immunostaining of the liver sections, the radiation resulted in the loss of the normal cell structure alongside a progressive and dose-dependent increase of the labelling, treatment, and pretreatment with rMnSOD, which had a significant protective effect on the livers. SM metabolic analyses, performed on aSMase and nSMase gene expression, as well as protein content and activity, proved that rMnSOD was able to significantly reduce radiation-induced damage by playing both a protective role via aSMase and a preventive role via nSMase

Multiwavelength observations of 3C 454.3. I. The AGILE 2007 November campaign on the "Crazy Diamond"

[Abridged] We report on a multiwavelength observation of the blazar 3C 454.3 (which we dubbed "crazy diamond") carried out on November 2007 by means of the astrophysical satellites AGILE, INTEGRAL, Swift, the WEBT Consortium, and the optical-NIR telescope REM. 3C 454.3 is detected at a $\sim 19-\sigma$ level during the 3-week observing period, with an average flux above 100 MeV of $F_{\rm E>100MeV} = (170 \pm 13) \times 10^{-8}$ \phcmsec. The gamma-ray spectrum can be fit with a single power-law with photon index $\Gamma_{\rm GRID} = 1.73 \pm 0.16$ between 100 MeV and 1 GeV. We detect significant day-by-day variability of the gamma-ray emission during our observations, and we can exclude that the fluxes are constant at the 99.6% ($\sim 2.9 \sigma$) level. The source was detected typically around 40 degrees off-axis, and it was substantially off--axis in the field of view of the AGILE hard X-ray imager. However, a 5-day long ToO observation by INTEGRAL detected 3C 454.3 at an average flux of about $F_{\rm 20-200 keV} = 1.49 \times 10^{-3}$ \phcmsec with an average photon index of $\Gamma_{\rm IBIS} = 1.75 \pm 0.24$ between 20--200 keV. Swift also detected 3C 454.3 with a flux in the 0.3--10 keV energy band in the range $(1.23-1.40) \times 10^{-2}$ \phcmsec{} and a photon index in the range $\Gamma_{\rm XRT} = 1.56-1.73$. In the optical band, both WEBT and REM show an extremely variable behavior in the $R$ band. A correlation analysis based on the entire data set is consistent with no time-lags between the gamma-ray and the optical flux variations. Our simultaneous multifrequency observations strongly indicate that the dominant emission mechanism between 30 MeV and 30 GeV is dominated by inverse Compton scattering of relativistic electrons in the jet on the external photons from the broad line region.Comment: Accepted for publication in ApJ. Abridged Abstract. 37 pages, 14 Figures, 3 Table

AGILE observation of a gamma-ray flare from the blazar 3C 279

Context. We report the detection by the AGILE satellite of an intense gamma-ray flare from the gamma-ray source 3EG J1255-0549, associated to the Flat Spectrum Radio Quasar 3C 279, during the AGILE pointings towards the Virgo Region on 2007 July 9-13. Aims. The simultaneous optical, X-ray and gamma-ray covering allows us to study the spectral energy distribution (SED) and the theoretical models relative to the flaring episode of mid-July. Methods. AGILE observed the source during its Science Performance Verification Phase with its two co-aligned imagers: the Gamma- Ray Imaging Detector (GRID) and the hard X-ray imager (Super-AGILE) sensitive in the 30 MeV - 50 GeV and 18 - 60 keV respectively. During the AGILE observation the source was monitored simultaneously in optical band by the REM telescope and in the X-ray band by the Swift satellite through 4 ToO observations. Results. During 2007 July 9-13 July 2007, AGILE-GRID detected gamma-ray emission from 3C 279, with the source at ~2 deg from the center of the Field of View, with an average flux of (210+-38) 10^-8 ph cm^-2 s^-1 for energy above 100 MeV. No emission was detected by Super-AGILE, with a 3-sigma upper limit of 10 mCrab. During the observation lasted about 4 days no significative gamma-ray flux variation was observed. Conclusions. The Spectral Energy Distribution is modelled with a homogeneous one-zone Synchrotron Self Compton emission plus the contributions by external Compton scattering of direct disk radiation and, to a lesser extent, by external Compton scattering of photons from the Broad Line Region.Comment: Accepted for publication in Astronomy and Astrophysic

Multiwavelength observations of 3C 454.3 II. The AGILE 2007 December campaign

We report on the second AGILE multiwavelength campaign of the blazar 3C 454.3 during the first half of December 2007. This campaign involved AGILE, Spitzer, Swift,Suzaku,the WEBT consortium,the REM and MITSuME telescopes,offering a broad band coverage that allowed for a simultaneous sampling of the synchrotron and inverse Compton (IC) emissions.The 2-week AGILE monitoring was accompanied by radio to optical monitoring by WEBT and REM and by sparse observations in mid-Infrared and soft/hard X-ray energy bands performed by means of Target of Opportunity observations by Spitzer, Swift and Suzaku, respectively.The source was detected with an average flux of~250x10^{-8}ph cm^-2s^-1 above 100 MeV,typical of its flaring states.The simultaneous optical and gamma-ray monitoring allowed us to study the time-lag associated with the variability in the two energy bands, resulting in a possible ~1-day delay of the gamma-ray emission with respect to the optical one. From the simultaneous optical and gamma-ray fast flare detected on December 12, we can constrain the delay between the gamma-ray and optical emissions within 12 hours. Moreover, we obtain three Spectral Energy Distributions (SEDs) with simultaneous data for 2007 December 5, 13, 15, characterized by the widest multifrequency coverage. We found that a model with an external Compton on seed photons by a standard disk and reprocessed by the Broad Line Regions does not describe in a satisfactory way the SEDs of 2007 December 5, 13 and 15. An additional contribution, possibly from the hot corona with T=10^6 K surrounding the jet, is required to account simultaneously for the softness of the synchrotron and the hardness of the inverse Compton emissions during those epochs.Comment: 13 pages, 8 figures, 2 tables, Accepted for publication in Ap

Expected performance of the ASTRI-SST-2M telescope prototype

ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) is an Italian flagship project pursued by INAF (Istituto Nazionale di Astrofisica) strictly linked to the development of the Cherenkov Telescope Array, CTA. Primary goal of the ASTRI program is the design and production of an end-to-end prototype of a Small Size Telescope for the CTA sub-array devoted to the highest gamma-ray energy region. The prototype, named ASTRI SST-2M, will be tested on field in Italy during 2014. This telescope will be the first Cherenkov telescope adopting the double reflection layout in a Schwarzschild-Couder configuration with a tessellated primary mirror and a monolithic secondary mirror. The collected light will be focused on a compact and light-weight camera based on silicon photo-multipliers covering a 9.6 deg full field of view. Detailed Monte Carlo simulations have been performed to estimate the performance of the planned telescope. The results regarding its energy threshold, sensitivity and angular resolution are shown and discussed.Comment: In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223