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The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

Mono-energetic carbon ion scanning beams of 195.2 MeV/u at the Italian National Centre for Oncological Hadrontherapy (CNAO) have been used to study the microdosimetric features of an “active” carbon ion beam used in hadrontherapy. A 30x30 mm2 area has been scanned by a 6 mm beam with scanning steps of 2 mm. A mini TEPC of 0.57 mm3 has been used to perform measurements in a water phantom at different depths on the beam axis. The detector small size allowed for measuring, with good spatial resolution, also inside the relatively small Bragg peak region and inside the distal edge, where the radiation quality varies quickly. In spite of the high event rate (up to ~ 105 s-1), no pile-up effects were observed. Results showed that the frequency-mean lineal energy scaled well with the absorbed dose. Moreover, the dose-mean lineal energy itself seemed to be a good descriptor of the radiation quality.

Objectives:To study the aetiology, outcome and prognostic indicators in children with acute liver failure (ALF).Study design:Retrospective chart review of 210 patients (107 males/103 females; median age: 5.33 years, range: 1–17.4). Patients were followed until discharge (group 1), death (group 2) or liver transplantation (LT; group 3). Data from group 1 were compared to data from the other two groups and King’s College criteria were also assessed.Results:Final diagnoses were: 128 (61%) hepatitis A, 68 (32%) indeterminate and 14 (7%) others. The characteristics of patients who survived (n = 59), died (n = 61) and underwent LT (n = 90) were analysed. In multivariate analysis, prothrombin time and encephalopathy III/IV were the most significant parameters suggesting a high likelihood of death. When King’s College criteria were applied on admission in patients with and without transplantation, the positive predictive values were 96% and 95%, and the negative predictive values were 82% and 82%, respectively.Conclusions:Hepatitis A is the main cause of ALF in children in Argentina. Advanced encephalopathy and prolonged prothrombin time were significantly associated with death or need for LT. King’s College criteria for predicting the outcome of ALF are applicable in children, including those with ALF due to hepatitis A infection.

•Argentina started universal single dose vaccination against hepatitis A in 2005.•An abrupt decline in cases occurred following this intervention.•Preventive medical and non-medical hepatitis A costs were assessed from 2000 to 2010.•Preventive, medical and non-medical costs decreased 2.6% in 2006–2010.•This strategy could be a good alternative in countries where hepatitis A is endemic. Vaccination against hepatitis A (HA) was carried out only as part of a limited outbreak control strategy in Argentina until June 2005, when universal immunization in infants was introduced into the national immunization calendar. A single-dose strategy was chosen instead of the standard two-dose schedule used elsewhere. This study aimed to estimate preventive, medical, and non-medical costs related to HA and to compare these costs in the periods before and after mass vaccination. A retrospective analysis estimated treatment costs of HA and unspecified hepatitis cases reported to the National Health Surveillance System from 2000 to 2010. Costs related to immunization, fulminant hepatitis (FH), liver transplantation, and death were projected as well. Using a social perspective and a healthcare system perspective, costs in two 5-year periods were compared: 2000–2004 versus 2006–2010. Finally, we evaluated the impact of different discount rates, FH risk, and exclusion of unspecified hepatitis cases in the sensitivity analysis. Total HA and unspecified hepatitis cases decreased from 157,871 in 2000–2004 to 17,784 in 2006–2010. Medical and non-medical costs decreased from US$11,811,600 and US$30,118,222 to US$1,252,694 and US$4,995,895 in those periods, respectively. Immunization costs increased from US$6,506,711 to US$40,912,132. Total preventive, medical, and non-medical costs decreased from US$48,436,534 to US$47,160,721, representing a 2.6% reduction in total costs between the two periods. When a healthcare system perspective was considered or unspecified hepatitis cases were excluded, total costs were 130.2% and 30.8% higher in 2006–2010 than in the previous period, respectively. After implementation of the universal single-dose vaccination against HA in infants in Argentina, an impressive decline was observed in HA cases, with a decrease in medical and non-medical costs in the first 5 years. The single-dose strategy, which is simpler and less expensive than the standard two-dose scheme, can be a good alternative for future vaccination policies in other countries where HA is endemic.

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement.

Purpose Many studies have demonstrated disparities in breast cancer (BC) incidence and mortality among Black women. We hypothesized that in Pennsylvania (PA), a large economically diverse state, BC diagnosis and mortality would be similar among races when stratified by a municipality’s median income. Methods We collected the frequencies of BC diagnosis and mortality for years 2011–2015 from the Pennsylvania Cancer Registry and demographics from the 2010 US Census. We analyzed BC diagnoses and mortalities after stratifying by median income, municipality size, and race with univariable and multivariable logistic regression models. Results In this cohort, of 5,353,875 women there were 54,038 BC diagnoses (1.01% diagnosis rate) and 9,828 BC mortalities (0.18% mortality rate). Unadjusted diagnosis rate was highest among white women (1.06%) but Black women had a higher age-adjusted diagnosis rate (1.06%) than white women (1.02%). Race, age and income were all significantly associated with BC diagnosis, but there were no differences in BC diagnosis between white and Black women across all levels of income in the multivariable model. BC mortality was highest in Black women, a difference which persisted when adjusted for age. Black women 35 years and older had a higher mortality rate in all income quartiles. Conclusion We found that in PA, age, race and income are all associated with BC diagnosis and mortality with noteworthy disparities for Black women. Continued surveillance of differences in both breast cancer diagnosis and mortality, and targeted interventions related to education, screening and treatment may help to eliminate these socioeconomic and racial disparities.

Purpose The aim of this study was to characterize the population pharmacokinetics of peginterferon (PEG-IFN) alfa-2b in pediatric patients with chronic hepatitis C and to identify covariates influencing PEG-IFN alfa-2b disposition. Methods Pharmacokinetic data from a multicenter open-label study of subcutaneously administered peginterferon alfa-2b (60 μg/m 2 /wk) plus oral ribavirin (15 mg/kg/day) in patients with chronic hepatitis C aged 3–17 years old was used to develop a population pharmacokinetic nonlinear mixed-effects model. Results The final population pharmacokinetic analysis was conducted with the pooled data from 107 pediatric patients. A one-compartment model with first-order absorption, first-order elimination, exponential inter-individual variability on clearance, and a combination additive and proportional residual error model adequately described the PEG-IFN alfa-2b pharmacokinetic profile. Age (apparent clearance and apparent volume of distribution) and sex (apparent clearance) were significant covariates. The mean body surface area normalized apparent clearance of PEG-IFN alfa-2b was 0.56 L/h/m 2 , and was similar when evaluated across the pediatric age groups. Conclusion The final population model suggests age-dependent increases in clearance and volume of distribution of PEG-IFN alfa-2b in pediatric patients with chronic hepatitis C. The apparent clearance normalized to body surface area was similar across pediatric age groups, supporting the use of body size–adjusted dosing in pediatric subjects.

The aim of this work was to study a possible use of carbon ion pencil beams (delivered with active scanning modality) for the treatment of ocular melanomas at the Centro Nazionale di Adroterapia Oncologica (CNAO). The promising aspect of carbon ions radiotherapy for the treatment of this disease lies in its superior relative radio-biological effectiveness (RBE). The Monte Carlo (MC) Geant4 10.00 toolkit was used to simulate the complete CNAO extraction beamline, with the active and passive components along it. A human eye modeled detector, including a realistic target tumor volume, was used as target. Cross check with previous studies at CNAO using protons allowed comparisons on possible benefits on using such a technique with respect to proton beams. Experimental data on proton and carbon ion beams transverse distributions were used to validate the simulation.

Charged particle therapy delivered using scanned pencil beams shows the potential to produce better dose conformity than conventional radiotherapy, although the dose distributions are more sensitive to anatomical changes and patient motion. Therefore, the introduction of engines to monitor the dose as it is being delivered is highly desirable, in order to enhance the development of adaptive treatment techniques in hadrontherapy. A tool for fast dose distributions analysis is presented, which integrates on GPU a Fast Forward Planning, a Fast Image Deformation algorithm, a fast computation of Gamma-Index and Dose-Volume Histogram. The tool is being interfaced with the Dose Delivery System and the Optical Tracking System of a synchrotron-based facility to investigate the feasibility to quantify, spill by spill, the effects of organ movements on dose distributions during treatment deliveries with protons and carbon-ions. The dose calculation and comparison times for a patient treated with protons on a 61.3 cm3 planning target volume, a CT matrix of 512x512x125 voxels, and a computation matrix of 170x170x125 voxels are within 1 s per spill. In terms of accuracy, the absolute dose differences compared with benchmarked Treatment Planning System results are negligible (<10-4 Gy).