Basal cell carcinoma: 10-year experience with electrochemotherapy

BACKGROUND: Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking. METHODS: In this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016. RESULTS: Disease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39-61%). Primary presentation (p = 0.004), tumor size <3 cm (p < 0.001), well-defined borders (p = 0.021), absence of tumor ulceration (p = 0.001), non-aggressive BCC histology (p = 0.046) and age 6469 years were associated with higher complete response rate. In patients with local BCC, the clearance rate was 72.5 and 85% after one or two ECT cycles, respectively. In the laBCC group, 32 patients (78%) achieved an objective response. Five-year recurrence rate for local and laBCC was 20 and 38%, respectively (p 64 0.001). CONCLUSIONS: One or two ECT cycles with bleomycin may be a valuable palliative treatment in well-selected patients with multiple BCCs and favorable tumor features. Validation of predictive factors will be imperative to match patients with optimal ECT treatment modalities. Management of laBCC with ECT warrants further investigation. Trial registration ISRCTN14633165 Registered 24 March 2017 (retrospectively registered)

Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors

BACKGROUND: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. METHODS: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). RESULTS: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade 653, 7.8%) was lower in patients with tumors <2 cm (p 640.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). CONCLUSIONS: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs

CAD-based computer vision: the automatic generation of recognition stragtegies

Journal ArticleThree-dimensional model-based computer vision uses geometric models of objects and sensed data to recognize objects in a scene. Likewise, Computer Aided Design (CAD) systems are used to interactively generate three-dimensional models during these fields. Recently, the unification of CAD and vision systems has become the focus of research in the context of manufacturing automation. This paper explores the connection between CAD and computer vision. A method for the automatic generation of recognition strategies based on the geometric properties of shape has been devised and implemented. This uses a novel technique developed for quantifying the following properties of features which compose models used in computer vision: robustness, completeness, consistency, cost, and uniqueness. By utilizing this information, the automatic synthesis of a specialized recognition scheme, called a Strategy Tree, is accomplished. Strategy Trees describe, in a systematic and robust manner. the search process used for recognition and localization of particular objects in the given scene. They consist of selected features which satisfy system constraints and Corroborating Evidence Subtrees which are used in the formation of hypotheses. Verification techniques, used to substantiate or refute these hypotheses, are explored. Experiments utilizing 3-D data are presented

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations

Studies of the mass composition of cosmic rays and proton-proton interaction cross-sections at ultra-high energies with the Pierre Auger Observatory

In this work, we present an estimate of the cosmic-ray mass composition from the distributions of the depth of the shower maximum (Xmax) measured by the fluorescence detector of the Pierre Auger Observatory. We discuss the sensitivity of the mass composition measurements to the uncertainties in the properties of the hadronic interactions, particularly in the predictions of the particle interaction cross-sections. For this purpose, we adjust the fractions of cosmic-ray mass groups to fit the data with Xmax distributions from air shower simulations. We modify the proton-proton cross-sections at ultra-high energies, and the corresponding air shower simulations with rescaled nucleus-air cross-sections are obtained via Glauber theory. We compare the energy-dependent composition of ultra-high-energy cosmic rays obtained for the different extrapolations of the proton-proton cross-sections from low-energy accelerator data

Study of downward Terrestrial Gamma-ray Flashes with the surface detector of the Pierre Auger Observatory

The surface detector (SD) of the Pierre Auger Observatory, consisting of 1660 water-Cherenkov detectors (WCDs), covers 3000 km2 in the Argentinian pampa. Thanks to the high efficiency of WCDs in detecting gamma rays, it represents a unique instrument for studying downward Terrestrial Gamma-ray Flashes (TGFs) over a large area. Peculiar events, likely related to downward TGFs, were detected at the Auger Observatory. Their experimental signature and time evolution are very different from those of a shower produced by an ultrahigh-energy cosmic ray. They happen in coincidence with low thunderclouds and lightning, and their large deposited energy at the ground is compatible with that of a standard downward TGF with the source a few kilometers above the ground. A new trigger algorithm to increase the TGF-like event statistics was installed in the whole array. The study of the performance of the new trigger system during the lightning season is ongoing and will provide a handle to develop improved algorithms to implement in the Auger upgraded electronic boards. The available data sample, even if small, can give important clues about the TGF production models, in particular, the shape of WCD signals. Moreover, the SD allows us to observe more than one point in the TGF beam, providing information on the emission angle

The dynamic range of the upgraded surface-detector stations of AugerPrime

The detection of ultra-high-energy cosmic rays by means of giant detector arrays is often limited by the saturation of the recorded signals near the impact point of the shower core at the ground, where the particle density dramatically increases. The saturation affects in particular the highest energy events, worsening the systematic uncertainties in the reconstruction of the shower characteristics. The upgrade of the Pierre Auger Observatory, called AugerPrime, includes the installation of an 1-inch Small PhotoMultiplier Tube (SPMT) inside each water-Cherenkov station (WCD) of the surface detector array. The SPMT allows an unambiguous measurement of signals down to about 250m from the shower core, thus reducing the number of events featuring a saturated station to a negligible level. In addition, a 3.8m2 plastic scintillator (Scintillator Surface Detector, SSD) is installed on top of each WCD. The SSD is designed to match the WCD (with SPMT) dynamic range, providing a complementary measurement of the shower components up to the highest energies. In this work, the design and performances of the upgraded AugerPrime surface-detector stations in the extended dynamic range are described, highlighting the accuracy of the measurements. A first analysis employing the unsaturated signals in the event reconstruction is also presented

Investigating multiple elves and halos above strong lightning with the fluorescence detectors of the Pierre Auger Observatory

ELVES are being studied since 2013 with the twenty-four FD Telescopes of the Pierre Auger Observatory, in the province of Mendoza (Argentina), the world’s largest facility for the study of ultra-high energy cosmic rays. This study exploits a dedicated trigger and extended readout. Since December 2020, this trigger has been extended to the three High levation Auger Telescopes (HEAT), which observe the night sky at elevation angles between 30 and 60 degrees, allowing a study of ELVES from closer lightning. The high time resolution of the Auger telescopes allows us to upgrade reconstruction algorithms and to do detailed studies on multiple ELVES. The origin of multiple elves can be studied by analyzing the time difference and the amplitude ratio between flashes and comparing them with the properties of radio signals detected by the ENTLN lightning network since 2018. A fraction of multi-ELVES can also be interpreted as halos following ELVES. Halos are disc-shaped light transients emitted at 70-80 km altitudes, appearing at the center of the ELVES rings, due to the rearrangement of electric charges at the base of the ionosphere after a strong lightning event