Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study

SIMPLE SUMMARY: The lung is the most frequent site of metastasis in Ewing sarcoma, the second most common bone cancer affecting children, adolescents and young adults. The five-year overall survival of patients with isolated lung metastasis is approximately 50% after multimodal treatments including chemotherapy, surgery and radiotherapy. This retrospective study aimed to investigate the feasibility and the predictors of survival in 68 Ewing sarcoma patients with lung metastases who received high-dose chemotherapy with busulfan and melphalan, followed by reduced dose whole-lung irradiation, as part of two prospective and consecutive treatment protocols. This combined treatment strategy is feasible and might contribute to the disease control in lung metastatic Ewing sarcoma with responsive disease. Furthermore, the results of this study provide support to explore the treatment stratification for lung metastatic Ewing sarcoma based on the histological response of the primary tumor. ABSTRACT: Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor

PixDD: a multi-pixel silicon drift detector for high-throughput spectral-timing studies

The Pixelated silicon Drift Detector (PixDD) is a two-dimensional multi-pixel X-ray sensor based on the technology of Silicon Drift Detectors, designed to solve the dead time and pile-up issues of photon-integrating imaging detectors. Read out by a two-dimensional self-triggering Application-Specific Integrated Circuit named RIGEL, to which the sensor is bump-bonded, it operates in the 0:5 — 15 keV energy range and is designed to achieve single-photon sensitivity and good spectroscopic capabilities even at room temperature or with mild cooling (< 150 eV resolution at 6 keV at 0 °C). The paper reports on the design and performance tests of the 128-pixel prototype of the fully integrated system

A Novel Mixed-Signal Silicon Photomultiplier with Analog-Domain Cross-Correlation Computation for LiDAR Applications

Light Detection and Ranging (LiDAR) is a widespread technique for distance measurements used in several applications. In this work, a novel Mixed-Signal Silicon Photomultiplier (msSiPM) with analog-domain cross-correlation computation for LiDAR applications is presented. Cross-correlation technique is commonly implemented at the end of the LiDAR system signal chain to estimate the Time-of-Flight (ToF) and to calculate the measured distance. In this work, an innovative way of performing an approximated cross-correlation inside the detector frontend is presented and simulated. In particular, the typical impulse response of an analog-SiPM (aSiPM) with a specific dead-time is replaced by a custom impulse response by means of a microcell-level Pulse Shaper stage. In this way, it is possible to tune the pulse to approximate the time-reversed shape of the laser envelope and to perform an analog cross-correlation. Simulations have been carried out in MATLAB software: by using an msSiPM instead of an aSiPM, an advantage in terms of Signal-to-Noise Ratio (SNR) of 6 dB and of Signal-to-Background Ratio (SBR) of about 23 dB is obtained

The sparse readout RIGEL Application Specific Integrated Circuit for Pixel Silicon Drift Detectors in soft X-ray imaging space applications

An Application Specific Integrated Circuit (ASIC), called RIGEL, designed for the sparse readout of a Silicon Pixel Drift Detector (PixDD) for space applications is presented. The low leakage current (less than 1 pA at +20 degrees C) and anode capacitance (less than 40 fF) of each pixel (300 mu m x 300 mu m) of the detector, combined with a low-noise electronics readout, allow to reach a high spectroscopic resolution performance even at room temperature. The RIGEL ASIC front-end architecture is composed by a 2-D matrix of 128 readout pixel cells (RPCs), arranged to host, in a 300 mu m-sided square area, a central octagonal pad (for the PixDD anode bump-bonding), and the full-analog processing chain, providing a full-shaped and stretched signal. In the chip periphery, the back-end electronics features 16 integrated 10-bits Wilkinson ADCs, the configuration register and a trigger management circuit. The characterization of a single RPC has been carried out whose features are: eight selectable peaking times from 0.5 mu s to 5 mu s, an input charge range equivalent to 30 keV, and a power consumption of less than 550 mu W per channel. The RPC has been tested also with a 4x4 prototype PixDD and 167 eV Full Width at Half Maximum (FWHM) at the 5.9 keV line of Fe-55 at 0 degrees C and 1.8 mu s of peaking time has been measured

The spatial side of somatoparaphrenia: a case study

The perception of the bodily self in space is a composite cognitive function requiring a dynamic integrated brain mechanism. Somatoparaphrenia (SP), a delusional belief concerning the experienced disownership for the contralesional paralyzed arm, represents the disruption of such mechanism. In two experiments, we have investigated the alteration of limb disownership after spatial manipulations in a right-brain-damaged patient affected by chronic SP. In experiment 1 the patient's spatial attention was switched between the left and right sides of space. SP signs worsened when the patient was interviewed from the left compared to the right bedside. In the second experiment we showed the first systematic transient remission of SP using left caloric vestibular stimulation (CVS), a physiologic manipulation mainly acting on the spatial frame of reference. Taken together, these results shed further light on the spatial nuance of SP and on the importance of vestibular signals for the generation of a coherent body representation. Furthermore, our case study demonstrated the possibility of eliciting more severe SP signs if the patient is interviewed from the left bedside. Additionally, CVS applications may have an important impact on the rehabilitation of these symptoms

Quantum ghost imaging based on a “looking back” 2D SPAD array

Quantum ghost imaging (QGI) is an intriguing imaging protocol that exploits photon-pair correlations stemming from spontaneous parametric down-conversion (SPDC). QGI retrieves images from two-path joint measurements, where single-path detection does not allow us to reconstruct the target image. Here we report on a QGI implementation exploiting a two-dimensional (2D) single-photon avalanche diode (SPAD) array detector for the spatially resolving path. Moreover, the employment of non-degenerate SPDC allows us to investigate samples at infrared wavelengths without the need for short-wave infrared (SWIR) cameras, while the spatial detection can be still performed in the visible region, where the more advanced silicon-based technology can be exploited. Our findings advance QGI schemes towards practical applications

A 100x100 CMOS SPAD Array with In-Pixel Correlation Techniques for Fast Quantum Ghost Imaging Applications

In this paper, a 100x100 CMOS Single Photon Avalanche Diode (SPAD) array designed for quantum imaging applications requiring synchronization with an external unpredictable and aperiodic trigger is presented. The targeted application takes advantage of non-classical quantum states of light to achieve quantum ghost imaging in the middle-infrared (MIR) up to 7 μm wavelength by detecting the corresponding entangled photons in the visible spectrum with the SPAD imager. For this purpose, a SPAD array with in-pixel backward-looking temporal correlation capabilities has been implemented to spatially resolve the entangled photons in a ghost imaging setup. The correlation is performed through a pixel-wise asynchronous delayed time window, whose width can be tuned to maximize the correlation efficiency. Two pixel variants, without and with resource sharing, have been designed: the resulting imager has been implemented in a 110 nm CIS FSI technology, achieving a correlation window width between 2 ns and 27 ns and a delay range between 5 ns and 40 ns, with 17 μm pixel pitch and fill-factor of 19.3% and 31.3%. A smart readout architecture has been implemented to improve the acquisition duty cycle, given the expected sparsity of the detected events

Synchronous bilateral Wilms tumor

BACKGROUND: The optimal management of bilateral Wilms tumor (BWT) is challenging, and their survival is lower than for unilateral tumors. This report discusses a large series of BWTs treated in Italy in the last 2 decades. METHODS: This analysis concerns patients with synchronous BWT registered at Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers between 1990 and 2011; details on their treatment and outcome are presented and discussed. RESULTS: Ninety BWTs were registered in the AIEOP Wilms tumor database. Preoperative chemotherapy was given for a median 12 weeks before definitive tumor resection was attempted. Forty-eight percent of the patients had preservation of bilateral renal parenchyma. The proportion of bilateral nephron-sparing surgeries was not higher in the 37 patients initially given doxorubicin/vincristine/actinomycin D (32%) than in the 43 children receiving vincristine/actinomycin D alone (58%). The 4-year disease-free survival rate was 66.5% \ub1 5% and overall survival was 80% \ub1 5% for the cohort as a whole. The 4-year disease-free survival (overall survival) for 18 children with diffuse anaplasia or postchemotherapy blastemal-type tumors was 51% \ub1 13% (62% \ub1 13%), as opposed to 72% \ub1 3% (88% \ub1 4%) for 68 children with a favorable histology (log-rank P = .04 [P = .007]). CONCLUSIONS: These results provide further evidence that the optimal duration and choice of drugs for preoperative chemotherapy remain an open question. Outcome remained significantly worse for BWT than for unilateral Wilms tumor. To enable the conservative treatment of as many affected kidneys as possible, only centers with experience in BWT should manage such case