Determination of ion recombination and polarity effect correction factors for a plane-parallel ionization Bragg peak chamber under proton and carbon ion pencil beams.

Within the dosimetric characterization of particle beams, laterally-integrated depth-dose-distributions (IDDs) are measured and provided to the treatment planning system (TPS) for beam modeling or used as a benchmark for Monte Carlo (MC) simulations. The purpose of this work is the evaluation, in terms of ion recombination and polarity effect, of the dosimetric correction to be applied to proton and carbon ion curves as a function of linear energy transfer (LET). LET was calculated with a MC code for selected IDDs. Several regions of Bragg peak (BP) curve were investigated. The charge was measured with the plane-parallel BP-ionization chamber mounted in the Peakfinder as a field detector, by delivering a fixed number of particles at the maximum flux. The dose rate dependence was evaluated for different flux levels. The chamber was connected to an electrometer and exposed to un-scanned pencil beams. For each measurement the chamber was supplied with {±400, +200, +100} V. Recombination and polarity correction factors were then calculated as a function of depth and LET in water. Three energies representative of the clinical range were investigated for both particle types. The corrected IDDs (IDD k s) were then compared against MC. Recombination correction factors were LET and energy dependent, ranging from 1.000 to 1.040 (±0.5%) for carbon ions, while nearly negligible for protons. Moreover, no corrections need to be applied due to polarity effect being <0.5% along the whole IDDs for both particle types. IDD k s showed a better agreement than uncorrected curves when compared to MC, with a reduction of the mean absolute variation from 1.2% to 0.9%. The aforementioned correction factors were estimated and applied along the IDDs, showing an improved agreement against MC. Results confirmed that corrections are not negligible for carbon ions, particularly around the BP region.

Monte Carlo simulation tool for online treatment monitoring in hadrontherapy with in-beam PET: A patient study.

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

Fred: a GPU-accelerated fast-Monte Carlo code for rapid treatment plan recalculation in ion beam therapy.

Ion beam therapy is a rapidly growing technique for tumor radiation therapy. Ions allow for a high dose deposition in the tumor region, while sparing the surrounding healthy tissue. For this reason, the highest possible accuracy in the calculation of dose and its spatial distribution is required in treatment planning. On one hand, commonly used treatment planning software solutions adopt a simplified beam-body interaction model by remapping pre-calculated dose distributions into a 3D water-equivalent representation of the patient morphology. On the other hand, Monte Carlo (MC) simulations, which explicitly take into account all the details in the interaction of particles with human tissues, are considered to be the most reliable tool to address the complexity of mixed field irradiation in a heterogeneous environment. However, full MC calculations are not routinely used in clinical practice because they typically demand substantial computational resources. Therefore MC simulations are usually only used to check treatment plans for a restricted number of difficult cases. The advent of general-purpose programming GPU cards prompted the development of trimmed-down MC-based dose engines which can significantly reduce the time needed to recalculate a treatment plan with respect to standard MC codes in CPU hardware. In this work, we report on the development of fred, a new MC simulation platform for treatment planning in ion beam therapy. The code can transport particles through a 3D voxel grid using a class II MC algorithm. Both primary and secondary particles are tracked and their energy deposition is scored along the trajectory. Effective models for particle-medium interaction have been implemented, balancing accuracy in dose deposition with computational cost. Currently, the most refined module is the transport of proton beams in water: single pencil beam dose-depth distributions obtained with fred agree with those produced by standard MC codes within 1-2% of the Bragg peak in the therapeutic energy range. A comparison with measurements taken at the CNAO treatment center shows that the lateral dose tails are reproduced within 2% in the field size factor test up to 20 cm. The tracing kernel can run on GPU hardware, achieving 10 million primary [Formula: see text] on a single card. This performance allows one to recalculate a proton treatment plan at 1% of the total particles in just a few minutes.

The FLUKA Monte Carlo code coupled with the NIRS approach for clinical dose calculations in carbon ion therapy.

Particle therapy facilities often require Monte Carlo (MC) simulations to overcome intrinsic limitations of analytical treatment planning systems (TPS) related to the description of the mixed radiation field and beam interaction with tissue inhomogeneities. Some of these uncertainties may affect the computation of effective dose distributions; therefore, particle therapy dedicated MC codes should provide both absorbed and biological doses. Two biophysical models are currently applied clinically in particle therapy: the local effect model (LEM) and the microdosimetric kinetic model (MKM). In this paper, we describe the coupling of the NIRS (National Institute for Radiological Sciences, Japan) clinical dose to the FLUKA MC code. We moved from the implementation of the model itself to its application in clinical cases, according to the NIRS approach, where a scaling factor is introduced to rescale the (carbon-equivalent) biological dose to a clinical dose level. A high level of agreement was found with published data by exploring a range of values for the MKM input parameters, while some differences were registered in forward recalculations of NIRS patient plans, mainly attributable to differences with the analytical TPS dose engine (taken as reference) in describing the mixed radiation field (lateral spread and fragmentation). We presented a tool which is being used at the Italian National Center for Oncological Hadrontherapy to support the comparison study between the NIRS clinical dose level and the LEM dose specification.

A phenomenological relative biological effectiveness approach for proton therapy based on an improved description of the mixed radiation field.

Proton therapy treatment planning systems (TPSs) are based on the assumption of a constant relative biological effectiveness (RBE) of 1.1 without taking into account the found in vitro experimental variations of the RBE as a function of tissue type, linear energy transfer (LET) and dose. The phenomenological RBE models available in literature are based on the dose-averaged LET (LET D ) as an indicator of the physical properties of the proton radiation field. The LET D values are typically calculated taking into account primary and secondary protons, neglecting the biological effect of heavier secondaries. In this work, we have introduced a phenomenological RBE approach which considers the biological effect of primary protons, and of secondary protons, deuterons, tritons (Z = 1) and He fragments (3He and 4He, Z = 2). The calculation framework, coupled with a Monte Carlo (MC) code, has been successfully benchmarked against clonogenic in vitro data measured in this work for two cell lines and then applied to determine biological quantities for spread-out Bragg peaks and a prostate and a head case. The introduced RBE formalism, which depends on the mixed radiation field, the dose and the ratio of the linear-quadratic model parameters for the reference radiation [Formula: see text], predicts, when integrated in an MC code, higher RBE values in comparison to LET D -based parameterizations. This effect is particular enhanced in the entrance channel of the proton field and for low [Formula: see text] tissues. For the prostate and the head case, we found higher RBE-weighted dose values up to about 5% in the entrance channel when including or neglecting the Z = 2 secondaries in the RBE calculation. TPSs able to proper account for the mixed radiation field in proton therapy are thus recommended for an accurate determination of the RBE in the whole treatment field.

Dosimetric commissioning and quality assurance of scanned ion beams at the Italian National Center for Oncological Hadrontherapy.

PURPOSE: To describe the dosimetric commissioning and quality assurance (QA) of the actively scanned proton and carbon ion beams at the Italian National Center for Oncological Hadrontherapy. METHODS: The laterally integrated depth-dose-distributions (IDDs) were acquired with the PTW Peakfinder, a variable depth water column, equipped with two Bragg peak ionization chambers. fluka Monte Carlo code was used to generate the energy libraries, the IDDs in water, and the fragment spectra for carbon beams. EBT3 films were used for spot size measurements, beam position over the scan field, and homogeneity in 2D-fields. Beam monitor calibration was performed in terms of number of particles per monitor unit using both a Farmer-type and an Advanced Markus ionization chamber. The beam position at the isocenter, beam monitor calibration curve, dose constancy in the center of the spread-out-Bragg-peak, dose homogeneity in 2D-fields, beam energy, spot size, and spot position over the scan field are all checked on a daily basis for both protons and carbon ions and on all beam lines. RESULTS: The simulated IDDs showed an excellent agreement with the measured experimental curves. The measured full width at half maximum (FWHM) of the pencil beam in air at the isocenter was energy-dependent for both particle species: in particular, for protons, the spot size ranged from 0.7 to 2.2 cm. For carbon ions, two sets of spot size are available: FWHM ranged from 0.4 to 0.8 cm (for the smaller spot size) and from 0.8 to 1.1 cm (for the larger one). The spot position was accurate to within ± 1 mm over the whole 20 × 20 cm(2) scan field; homogeneity in a uniform squared field was within ± 5% for both particle types at any energy. QA results exceeding tolerance levels were rarely found. In the reporting period, the machine downtime was around 6%, of which 4.5% was due to planned maintenance shutdowns. CONCLUSIONS: After successful dosimetric beam commissioning, quality assurance measurements performed during a 24-month period show very stable beam characteristics, which are therefore suitable for performing safe and accurate patient treatments.

Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation.

This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo(®) TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus(®) chamber. An EBT3(®) film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

Economic analysis of the single-dose immunization strategy against hepatitis A in Argentina.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 vivo radiobiological assessment of the new clinical carbon ion beams at CNAO.

In this article, the in vivo study performed to evaluate the uniformity of biological doses within an hypothetical target volume and calculate the values of relative biological effectiveness (RBE) at different depths in the spread-out Bragg peak (SOBP) of the new CNAO (National Centre for Oncological Hadrontherapy) carbon beams is presented, in the framework of a typical radiobiological beam calibration procedure. The RBE values (relative to (60)Co γ rays) of the CNAO active scanning carbon ion beams were determined using jejunal crypt regeneration in mice as biological system at the entrance, centre and distal end of a 6-cm SOBP. The RBE values calculated from the iso-effective doses to reduce crypt survival per circumference to 10, ranged from 1.52 at the middle of the SOBP to 1.75 at the distal position and are in agreement with those previously reported from other carbon ion facilities. In conclusion, this first set of in vivo experiments shows that the CNAO carbon beam is radiobiologically comparable with the NIRS (National Institute of Radiological Sciences, Chiba, Japan) and GSI (Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany) ones.

Development and application of tools for Monte Carlo based simulations in a particle beam radiotherapy facility.

The integration of Monte Carlo (MC) transport codes into a particle therapy facility could be more easily achieved thanks to dedicated software tools. MC approach has been applied to several purposes at CNAO (Centro Nazionale di Adroterapia Oncologica), such as database generation for the treatment planning system, quality assurance calculations and biologically related simulations. In this paper we describe another application of the MC code and its tools by analyzing the impact of the dose delivery and range uncertainties on patient dose distributions.

Dosimetric accuracy assessment of a treatment plan verification system for scanned proton beam radiotherapy: one-year experimental results and Monte Carlo analysis of the involved uncertainties.

During one year of clinical activity at the Italian National Center for Oncological Hadron Therapy 31 patients were treated with actively scanned proton beams. Results of patient-specific quality assurance procedures are presented here which assess the accuracy of a three-dimensional dose verification technique with the simultaneous use of multiple small-volume ionization chambers. To investigate critical cases of major deviations between treatment planning system (TPS) calculated and measured data points, a Monte Carlo (MC) simulation tool was implemented for plan verification in water. Starting from MC results, the impact of dose calculation, dose delivery and measurement set-up uncertainties on plan verification results was analyzed. All resulting patient-specific quality checks were within the acceptance threshold, which was set at 5% for both mean deviation between measured and calculated doses and standard deviation. The mean deviation between TPS dose calculation and measurement was less than ±3% in 86% of the cases. When all three sources of uncertainty were accounted for, simulated data sets showed a high level of agreement, with mean and maximum absolute deviation lower than 2.5% and 5%, respectively.

[Risk assessment: use of the SOBANE model at the Health Authority of Lodi province]. / La valutazione del rischio: applicazione del modello SOBANE nell'ASL di Lodi.

The evaluation of the risks for the health safeguard within the workplace, represents a fundamental moment of the intervention planning. During the years it has been enriched by experiences, improvements and techniques essentially introduced by a set of laws; in particular the 626/94 Legislative Decree. This was the first well-organized expression of the new strategies identified on the basis of the assigned responsibilities and the protection of the production process. With the 81/08 L.D. such strategies have been once again highlighted but with a particular emphasis on the partecipation of the workers in the risk detection. This work just deals with such aspect by means of the experimentation of a specific method represented by the so called SOBANE pattern. The results point out some aspects that are positive in terms of satisfaction and handiness. These aspects may contribute to the employment of the method to a wide range of services with important effects on the drawing up of the evaluation document of the business risks

Fallo hepático fulminante por hepatitis a: evolución y costos / Fulminant liver failure caused by hepatitis A: outcome and cost

La hepatitis A (HA) es una de las enfermedades inmunoprevenibles más frecuente, constituye actualmente en nuestro país un grave problema de la Salud Pública, por su alta incidencia 40/100.000 habitantes según informe del SINAVE 2002. La complicación más severa es el fallo Hepático fulminante (FHF), emergencia médica que se presenta en el 1/1000 de los pacientes sintomáticos infectados por virus de hepatitis A (VHA). Las tasas de morbimortalidad del FHF continúan siendo altas, lo que genera importantes costos. Nuestro objetivo fue analizar características, evolución y costos de la población internada por FHF secundario a VHA con indicación de trasplante hepático (TXH) en el Hospital de Pediatría Juan P. Garrahan, en el período comprendido entre noviembre de 1992 a junio de 2003. Se analizó: Lugar de procedencia, edad, días de internación en cuidados intermedios (CIM) y/o intensivos (UCI) y evolución. Los costos se obtuvieron del Departamento de Costos del hospital. Para evaluar el tiempo perdido por muerte prematura, utilizamos el cálculo de los años de vida potencial perdidos. Durante el período de estudio se realizaron 308 trasplantes hepáticos. Fueron asistidos por Falla Hepática Fulminante 145 pacientes (p) de ellos el 58 por ciento (p:84) fueron Hepatitis por Virus de Hepatitis A. La edad media de los niños fue de 4.6 años (1a-11a). Los datos de la evolución fueron: el 20 por ciento (n:17) fallecieron en lista de espera de emergencia, el 11 por ciento (n:9). la función hepática se recuperó antes que el injerto apareciera, el 69% (n:58) fueron trasplantados. El TXH se realizó con donante cadavérico en el 90% (n:52) de los casos, se utilizó donante vivo relacionado en el 10 por ciento (n:6). Requirieron retrasplante el (19 por ciento) (n: 11). La mortalidad del FHF por VHA fue del 38 por ciento (n:32). La mortalidad por trasplante hepático fue del 26 por ciento (n:15). Los años perdidos por muerte prematura fueron 2.275 años.