preoperative therapy with trastuzumab and oral vinorelbine endocrine therapy in patients with her2 positive breast cancer

Abstract Background Combined trastuzumab and intravenous vinorelbine yielded high clinical activity as preoperative treatment in patients (pts) with HER 2/ neu positive breast cancer. Patients and methods We tested a preoperative combination of trastuzumab with oral vinorelbine (oV) in pts with locally advanced (T2-T4 N0-3 M0) HER2-positive breast cancer. Trastuzumab was administered i.v q 3 wks and oV was administered at the dose of 55 mg/sqm on days 1 and 3 q 3 wks, for 8 courses. Pts with ER ≥ 10% tumors received endocrine therapy with letrozole 2.5 mg/day, plus monthly triptorelin if premenopausal. Results Forty-five pts entered the study. The overall response rate (CR + PR) was 76% (95% CI: 60%–87%). pCR was observed in 4 pts (10%). Among ER-positive tumors 21/25 pts obtained a clinical response (84%) and two pts obtained a pCR (8%). Conclusions The combination of trastuzumab and oral vinorelbine demonstrated encouraging activity in patients with HER 2 positive ER-positive tumors. Alternative strategies should be investigated in patients with endocrine non responsive disease

increased mean corpuscular volume of red blood cells predicts response to metronomic capecitabine and cyclophosphamide in combination with bevacizumab

Abstract Background There is an urgent need for the identification of commonly assessable predictive factors in the treatment of patients with metastatic breast cancer. Methods During the course of a treatment including low dose metronomic oral cyclophosphamide and capecitabine plus i.v. bevacizumab (plus erlotinib in one third of the patients) for metastatic breast cancer, we observed that a relevant number of patients developed repeatedly elevated levels of mean corpuscular volume (MCV) of red blood cells without a significant fall in hemoglobin levels. We conducted a retrospective analysis on these 69 patients to evaluate if the increase in MCV could be associated to tumor response. Results During the course of treatment 42 out of 69 patients (61%) developed macrocytosis. Using Cox proportional hazards modeling that incorporated macrocytosis (MCV≥100 fl) as a time-dependent covariate, macrocytosis resulted in a halved risk of disease progression (HR 0.45; 95% CI, 0.22–0.92, p-value 0.028). In a landmark analysis limited to patients with no sign of progression after 24 weeks of treatment, median time to progression was 72 weeks (48 weeks after landmark) in patients who had developed macrocytosis, and 43 weeks (19 weeks after landmark) in patients who had not (p = 0.023). Conclusion Macrocytosis inversely related to risk of disease progression in patients treated with metronomic capecitabine plus cyclophosphamide and bevacizumab for metastatic breast cancer. This finding may be explained through thymidylate synthase inhibition by capecitabine. Whether bevacizumab has a role in determining macrocytosis, similarly to what happens with sunitinib, has to be further investigated. If other studies will confirm our findings, macrocytosis might be used as an early marker of response during metronomic treatment with capecitabine and cyclophosphamide with or without bevacizumab

Erratum to: Oncoplastic Breast-Conserving Surgery for Tumors Larger than 2 Centimeters: Is it Oncologically Safe? A Matched-Cohort Analysis

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Integrated petrological and geophysical constraints on magma system architecture in the western Galápagos Archipelago: insights from Wolf volcano

The 2015 eruption of Wolf volcano was one of the largest eruptions in the Galápagos Islands since the onset of routine satellite-based volcano monitoring. It therefore provides an excellent opportunity to combine geophysical and petrological data, to place detailed constraints on the architecture and dynamics of sub-volcanic systems in the western archipelago. We present new geodetic models which show that pre-eruptive inflation at Wolf was caused by magma accumulation in a shallow flat-topped reservoir at ~1.1 km, whereas edifice-scale deformation during the eruption was related to a deflationary source at 6.1–8.8 km. Petrological observations suggest that the erupted material was derived from both a sub-volcanic mush and a liquid-rich magma body. Using a combination of olivine-plagioclase-augite-melt (OPAM) and clinopyroxene-melt barometry, we show that the majority of magma equilibration, crystallisation and mush entrainment occurred at a depth equal to or greater than the deep geodetic source, with little petrological evidence of material sourced from shallower levels. Hence, our multidisciplinary study does not support a fully trans-crustal magmatic system beneath Wolf volcano before the 2015 eruption, but instead indicates two discrete storage regions, with a small magma lens at shallow levels and the major zone of magma storage in the lower crust, from which most of the erupted material was sourced. A predominance of lower crustal magma storage has previously been thought typical of sub-volcanic systems in the eastern Galápagos Archipelago, but our new data suggest that this may also occur beneath the more active volcanoes of the western archipelago

Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands.

Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems

The 2014–2015 eruption of Fogo volcano: Geodetic modeling of Sentinel-1 TOPS interferometry

After 20 years of quiescence, Fogo volcano erupted in November 2014. The eruption produced fast-moving lava flows that traveled for several kilometers and destroyed two villages. This event represents the first episode of significant surface deformation imaged by the new European Space Agency's Sentinel-1 satellite in its standard acquisition mode, Terrain Observation by Progressive Scans (TOPS), which differs from that of previous synthetic aperture radar (SAR) missions. We perform a Bayesian inversion of Sentinel-1 TOPS SAR interferograms spanning the eruption and accurately account for variations in the TOPS line-of-sight vector when modeling displacements. Our results show that magma ascended beneath the Pico do Fogo cone and then moved laterally toward its southwestern flank, where the eruptive fissure opened. This study provides important insights into the inner workings of Fogo volcano and shows the potential of Sentinel-1 TOPS interferometry for geophysical (e.g., volcano monitoring) applications

Evolution of deformation and stress changes during the caldera collapse and dyking at Bárdarbunga, 2014–2015: Implication for triggering of seismicity at nearby Tungnafellsjökull volcano

Stress transfer associated with an earthquake, which may result in the seismic triggering of aftershocks (earthquake–earthquake interactions) and/or increased volcanic activity (earthquake–volcano interactions), is a well-documented phenomenon. However limited studies have been undertaken concerning volcanic triggering of activity at neighbouring volcanoes (volcano–volcano interactions). Here we present new deformation and stress modelling results utilising a wealth of diverse geodetic observations acquired during the 2014–2015 unrest and eruption within the Bárdarbunga volcanic system. These comprise a combination of InSAR, GPS, LiDAR, radar profiling and optical satellite measurements. We find a strong correlation between the locations of increased seismicity at nearby Tungnafellsjökull volcano and regions of increased tensile and Coulomb stress changes. Our results suggest that stress transfer during this major event has resulted in earthquake triggering at the neighbouring Tungnafellsjökull volcano by unclamping faults within the associated fissure swarm. This work has immediate application to volcano monitoring; to distinguish the difference between stress transfer and new intrusive activity

Integration of SAR Data Into Monitoring of the 2014-2015 Holuhraun Eruption, Iceland: Contribution of the Icelandic Volcanoes Supersite and the FutureVolc Projects

We report how data from satellite and aerial synthetic aperture radar (SAR) observations were integrated into monitoring of the 2014–2015 Holuhraun eruption in the Bárðarbunga volcanic system, the largest effusive eruption in Iceland since the 1783–84 Laki eruption. A lava field formed in one of the most remote areas in Iceland, after the propagation of a ∼50 km-long dyke beneath the Vatnajökull ice cap, where the Bárðarbunga caldera is located. Due to the 6 month duration of the eruption, mainly in wintertime, daily monitoring was particularly challenging. During the eruption, the European volcanological project FutureVolc was ongoing, allowing collaboration of many European experts on volcano monitoring activities. Icelandic volcanoes are also a permanent Supersite within the Geohazard Supersites and Natural Laboratories (GSNL) initiative, with support from the Committee on Earth Observation Satellite (CEOS) in the form of a large collection of SAR images. SAR data were acquired by Cosmo-SkyMed (CSK) and TerraSAR-X (TSX) satellites and complemented by aerial SAR images. The large set of SAR satellite data significantly contributed to the daily monitoring during the unrest at Bárðarbunga caldera, the Holuhraun eruption and the year following the eruption. Detection of surface changes using both SAR amplitude and phase information was conducted throughout the whole duration of the volcano-tectonic event, and in the following months, to quantify and track the evolution of volcanic processes at Holuhraun and geothermal activity at Bárðarbunga volcano. Combination of SAR data with other data sets, e.g., satellite optical images and geodetic Global Positioning System (GPS) measurements, was essential for the evaluation of the volcanic hazard in the whole area. International collaboration within the FutureVolc project formed the basis for successful analyses and interpretation of the large SAR data set. Information was provided at Scientific Advisory Board meetings of the Icelandic Civil Protection and used in decision-making, as well as for supporting field-deployment and air-based surveys

Gradual caldera collapse at Bárdarbunga volcano, Iceland, regulated by lateral magma outflow

Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption.We usemultiparameter geophysical and geochemical data to show that the 110-squarekilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014-2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, nearexponential decline of both collapse rate and the intensity of the 180-day-long eruption.</p