Numerical Study of Carbon Nanofoam Targets for Laser-Driven Inertial Fusion Experiments

Porous materials have peculiar characteristics that are relevant for inertial confinement fusion (ICF). Among them, chemically produced foams are proved to be able to smooth the laser inhomogeneities and to increase the coupling of the laser with the target. Foams realized with other elements and techniques may prove useful as well for ICF applications. In this work, we explore the potential of a novel class of porous materials for ICF, namely, carbon nanofoams produced with the pulsed laser deposition (PLD) technique, by means of hydrodynamic numerical simulations. By comparison with a simulation of solid-density carbon, PLD nanofoams show a higher pressure at the shock front, which could make them potential good candidates as ablators for a capsule for direct-drive fusion

RENO, a European Postmarket Surveillance Registry, confirms effectiveness of coronary brachytheraypy in routine clinical practice.

Purpose: To assess, by a European registry trial, the clinical event rate in patients with discrete stenotic lesions of coronary arteries (de novo or restenotic) in single or multiple vessels (native or bypass grafts) treated with -radiation. Methods and Materials: Between April 1999 and September 2000, 1098 consecutive patients treated in 46 centers in Europe and the Middle East with the Novoste Beta-Cath System were included in Registry Novoste (RENO). Results: Six-month follow-up data were obtained for 1085 patients. Of 1174 target lesions, 94.1% were located in native vessels and 5.9% in a bypass graft; 17.7% were de novo lesions, 4.1% were restenotic, and 77.7% were in-stent restenotic lesions. Intravascular brachytherapy was technically successful in 95.9% of lesions. Multisegmental irradiation, using a manual pullback stepping maneuver to treat longer lesions, was used in 16.3% of the procedures. The in-hospital rate of major adverse cardiac events was 1.8%. At 6 months, the rate was 18.7%. Angiographic follow-up was available for 70.4% of the patients. Nonocclusive restenosis was seen in 18.8% and total occlusion in 5.7% of patients. A combined end point for late (30–180 days) definitive or suspected target vessel closure was reached in 5.4%, but with only 2% of clinical events. Multivariate analysis was performed for major adverse cardiac events and late thrombosis. Conclusion: Data obtained from the multicenter RENO registry study, derived from a large cohort of unselected consecutive patients, suggest that the good results of recent randomized controlled clinical trials can be replicated in routine clinical practice. © 2003 Elsevier Science Inc

Nephrological Complications in Hemoglobinopathies: SITE Good Practice

Background. Hemoglobinopathies, among which thalassemic syndromes (transfusion-dependent and non-transfusion dependent thalassemias) and sickle cell disease (SCD), are the most widespread monogenic diseases worldwide. Hemoglobinopathies are endemic and spread-out all-over Italy, as result of internal and external migration flows. Nowadays, the increase therapeutic options associated to the general aging of patients with hemoglobinopathies related to the improvement in clinical management, contribute to the abnormalities in kidney function going from blood and urine test alterations to chronic kidney disease and end stage renal disease. Methods. Here, we carried out a revision of the literature as panel of recognized experts in hemoglobinopathies with the consultancy and the revision of two nephrologists on kidney alteration and kidney disease in patients with TDT, NTDT and SCD. This is part of the action of the Italian society for the study of thalassemia and hemoglobinopties (SITE). The purpose of this “good practice (GP)” is to provide recommendations for follow-up and therapy for the management of kidney alterations in patients with TDT, NTDT and SCD. The literature review covers the period 1.1.2016 to 31.12.2022. In consideration of the rarity of these diseases, the analysis was extended from 5 to 7 years. Moreover, in the absence of relevant scientific papers in the identified time frame, we referred to pivotal or population studies, when available. Finally, in the absence of evidence-based data from prospective and randomized trials, the authors had to refer to expert opinion (expert consensus) for many topics. Results. We generated question and answer boxes to offer a friendly consultation, using color code strategy and focused answers. Conclusions. The present GP will help in improving the clinical management, and the quality of care of patients with hemoglobinopathies

po 237 the pro oncogenic transcription factor stat3 regulates ca2 release and apoptosis from the endoplasmic reticulum via interaction with the ca2 channel ip3r3

Introduction Signal Transducer and Activator of Transcription (STAT) 3 is an oncogenic transcription factor found constitutively activated in several tumours, where it exerts its functions both as a canonical transcription factor and as a non-canonical regulator of energy metabolism and mitochondrial functions. These two activities rely on different post-translational activating events; the phosphorylation on Y705 is involved in nuclear activities, while that on S727 is relevant for mitochondrial functions. Mitochondrial STAT3 increases aerobic glycolysis and decreases ROS production, partly by interacting with the Electron Transfer Complexes (ETC). Material and methods By means of cell fractionations, we tested STAT3 localization to the Endoplasmic Reticulum (ER) in breast cancer cell lines dependent or not on STAT3 activity. We then measured Ca2+ release and apoptotic response in the same cells. The physical interaction between inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) and STAT3 was demonstrated by co-IP either of the endogenous proteins or of their truncated/mutated forms, while STAT3 role in the degradation of IP3R3 was tested by serum starvation and refeeding experiments, followed by WB. Results and discussions We describe here the previously undetected abundant localization of STAT3 also to the ER. In this cellular compartment IP3R3, a Ca2+ channel that allows Ca2+ release from the ER and the mitochondrial associated membranes (MAMs) in response to IP3, regulates the balance between mitochondrial activation and Ca2+-triggered apoptosis. We observed that STAT3 within the ER physically interacts with IP3R3 and, via its phosphorylation on S727, it down-regulates Ca2+ release and apoptosis. Indeed, STAT3 silencing enhances both ER Ca2+ release and sensitivity to apoptosis following oxidative stress in STAT3-dependent mammary tumour cells, correlating with increased IP3R3 levels. In line with this, basal-like breast tumours, which frequently display constitutively active STAT3, show an inverse correlation between IP3R3 and STAT3 protein levels. Conclusion Our results indicate that S727-phosphorylated STAT3 contribute to mammary tumour aggressiveness, also by localising to the ER and regulating Ca2+ fluxes. STAT3-mediated enhanced IP3R3 degradation leads to decreased Ca2+ release and thus to resistance to apoptosis. This new non-canonical STAT3 role appears to be particularly relevant in basal-like breast cancers, adding a new mechanisms through which STAT3 exerts its well established pro-oncogenic anti-apoptotic role

Quality of life in patients with chordomas/chondrosarcomas during treatment with proton beam therapy

Introduction: Health-related quality of life (HQL) parameters have never been tested in patients having chondromas/chondrosarcomas who are being treated with protons. The aim of this study was to document changes in HQL of chordoma/chondrosarcoma patients treated with proton beam radiotherapy. Treatments commenced in September 2011 at CNAO, and HQL studies were initiated in January 2012 for all patients undergoing treatment. Methods: The validated Italian translation of the EORTC QLQ-C30 version 3.0 was used for HQL evaluation. The HQL assessments were made prior to starting radiation and at completion of treatment. Scoring was as per the EORTC manual. As per standard norms, a difference of >10 points in the mean scores was taken to be clinically meaningful. Results: Between January and September 2012, 17 patients diagnosed with chordoma or chondrosarcoma, with a mean \ub1 SD age of 49.5 \ub1 16.4 years, had completed treatment. The involved sites were skull base (n = 12) and sacral/paraspinal (n = 5). The prescribed dose was 70-74 GyE at 2 GyE per fraction, 5 days/week. When comparing pre- and post-treatment scores, neither a clinically meaningful nor a statistically significant change was documented. Conclusions: During treatment, HQL is not adversely affected by protons, allowing normal life despite the long course of treatment. This is an ongoing study and more long-term assessment will help evaluate the actual impact of proton therapy on HQL for these slow-responding tumours

VERO (R) radiotherapy for low burden cancer: 789 patients with 957 lesions

Purpose: The aim of this retrospective study is to evaluate patient profile, feasibility, and acute toxicity of RadioTherapy (RT) delivered by VERO\uae in the first 20 months of clinical activity. Methods: Inclusion criteria: 1) adult patients; 2) limited volume cancer (M0 or oligometastatic); 3) small extracranial lesions; 4) treatment between April 2012 and December 2013 and 5) written informed consent. Two techniques were employed: intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). Toxicity was evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria. Results: Between April 2012 and December 2013, 789 consecutive patients (957 lesions) were treated. In 84% of them one lesion was treated and in 16% more than one lesion were treated synchronously/metachronously; first radiotherapy course in 85%, re-irradiation in 13%, and boost in 2% of cases. The treated region included pelvis 46%, thorax 38%, upper abdomen 15%, and neck 1%. Radiotherapy schedules included <5 and >5 fractions in 75% and 25% respectively. All patients completed the planned treatment and an acceptable acute toxicity was observed. Conclusions: RT delivered by VERO\uae was administrated predominantly to thoracic and pelvic lesions (lung and urologic tumours) using hypofractionation. It is a feasible approach for limited burden cancer offering short and well accepted treatment with favourable acute toxicity profile. Further investigation including dose escalation and other available VERO\uae functionalities such as real-time dynamic tumour tracking is warranted in order to fully evaluate this innovative radiotherapy system

IART® (Intra-Operative Avidination for Radionuclide Therapy) for accelerated radiotherapy in breast cancer patients. Technical aspects and preliminary results of a phase II study with 90Y-labelled biotin

Background: Breast conserving surgery (BCS) plus external beam radiotherapy (EBRT) is considered the standard treatment for early breast cancer. We have investigated the possibility of irradiating the residual gland, using an innovative nuclear medicine approach named IART® (Intra-operative Avidination for Radionuclide Therapy). Aim: The objective of this study was to determine the optimal dose of avidin with a fixed activity (3.7 GBq) of 90Y-biotin, in order to provide a boost of 20 Gy, followed by EBRT to the whole breast (WB) at the reduced dose of 40 Gy. Local and systemic toxicity, patient's quality of life, including the cosmetic results after the combined treatment with IART® and EBRT, were assessed. Methods: After tumour excision, the surgeon injected native avidin diluted in 30 ml of saline solution into and around the tumour bed (see video). Patients received one of three avidin dose levels: 50 mg (10 pts), 100 mg (15 pts) and 150 mg (10 pts). Between 12 to 24 h after surgery, 3.7 GBq 90Y-biotin spiked with 185 MBq 111In-biotin was administered intravenously (i.v.). Whole body scans and SPECT images were performed up to 30 h post-injection for dosimetric purposes. WB-EBRT was administered four weeks after the IART® boost. Local toxicity and quality of life were evaluated. Results: Thirty-five patients were evaluated. No side effects were observed after avidin administration and 90Y-biotin infusion. An avidin dose level of 100 mg resulted the most appropriate in order to deliver the required radiation dose (19.5 + 4.0 Gy) to the surgical bed. At the end of IART®, no local toxicity occurred and the overall cosmetic result was good. The tolerance to the reduced EBRT was also good. The highest grade of transient local toxicity was G3, which occurred in 3/32 pts following the completion of WB-EBRT. The combination of IART® +EBRT was well accepted by the patients, without any changes to their quality of life. Conclusions: These preliminary results support the hypothesis that IART® may represent a valid approach to accelerated WB irradiation after BCS. We hope that this nuclear medicine technique will contribute to a better management of breast cancer patients. © the authors; licensee ecancermedicalscience

Initial clinical experience with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO)

We report the initial toxicity data with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO). In September 2011, CNAO commenced patient treatment with scanned proton beams within two prospective Phase II protocols approved by the Italian Health Ministry. Patients with chondrosarcoma or chordoma of the skull base or spine were eligible. By October 2012, 21 patients had completed treatment. Immobilization was performed using rigid non-perforated thermoplastic-masks and customized headrests or body-pillows as indicated. Non-contrast CT scans with immobilization devices in place and MRI scans in supine position were performed for treatment-planning. For chordoma, the prescribed doses were 74 cobalt grey equivalent (CGE) and 54 CGE to planning target volume 1 (PTV1) and PTV2, respectively. For chondrosarcoma, the prescribed doses were 70 CGE and 54 CGE to PTV1 and PTV2, respectively. Treatment was delivered five days a week in 35-37 fractions. Prior to treatment, the patients' positions were verified using an optical tracking system and orthogonal X-ray images. Proton beams were delivered using fixed-horizontal portals on a robotic couch. Weekly MRI incorporating diffusion-weighted-imaging was performed during the course of proton therapy. Patients were reviewed once weekly and acute toxicities were graded with the Common Terminology Criteria for Adverse Events (CTCAE). Median age of patients = 50 years (range, 21-74). All 21 patients completed the proton therapy without major toxicities and without treatment interruption. Median dose delivered was 74 CGE (range, 70-74). The maximum toxicity recorded was CTCAE Grade 2 in four patients. Our preliminary data demonstrates the clinical feasibility of scanned proton beams in Italy