Robustness evaluation of pencil beam scanning proton therapy treatment planning: A systematic review.

Compared to conventional radiotherapy using X-rays, proton therapy, in principle, allows better conformity of the dose distribution to target volumes, at the cost of greater sensitivity to physical, anatomical, and positioning uncertainties. Robust planning, both in terms of plan optimization and evaluation, has gained high visibility in publications on the subject and is part of clinical practice in many centers. However, there is currently no consensus on the methods and parameters to be used for robust optimization or robustness evaluation. We propose to overcome this deficiency by following the modified Delphi consensus method. This method first requires a systematic review of the literature. We performed this review using the PubMed and Web Of Science databases, via two different experts. Potential conflicts were resolved by a third expert. We then explored the different methods before focusing on clinical studies that evaluate robustness on a significant number of patients. Many robustness assessment methods are proposed in the literature. Some are more successful than others and their implementation varies between centers. Moreover, they are not all statistically or mathematically equivalent. The most sophisticated and rigorous methods have seen more limited application due to the difficulty of their implementation and their lack of widespread availability.

Virtual 4DCT generated from 4DMRI in gated particle therapy: phantom validation and application to lung cancer patients.

Objective. Respiration negatively affects the outcome of a radiation therapy treatment, with potentially severe effects especially in particle therapy (PT). If compensation strategies are not applied, accuracy cannot be achieved. To support the clinical practice based on 4D computed tomography (CT), 4D magnetic resonance imaging (MRI) acquisitions can be exploited. The purpose of this study was to validate a method for virtual 4DCT generation from 4DMRI data for lung cancers on a porcine lung phantom, and to apply it to lung cancer patients in PT.Approach. Deformable image registration was used to register each respiratory phase of the 4DMRI to a reference phase. Then, a static 3DCT was registered to this reference MR image set, and the virtual 4DCT was generated by warping the registered CT according to previously obtained deformation fields. The method was validated on a physical phantom for which a ground truth 4DCT was available and tested on lung tumor patients, treated with gated PT at end-exhale, by comparing the virtual 4DCT with a re-evaluation 4DCT. The geometric and dosimetric evaluation was performed for both proton and carbon ion treatment plans.Main results. The phantom validation exhibited a geometrical accuracy within the maximum resolution of the MRI and mean dose deviations, with respect to the prescription dose, up to 3.2% for targetD95%, with a mean gamma pass rate of 98%. For patients, the virtual and re-evaluation 4DCTs showed good correspondence, with errors on targetD95%up to 2% within the gating window. For one patient, dose variations up to 10% at end-exhale were observed due to relevant inter-fraction anatomo-pathological changes that occurred between the planning and re-evaluation CTs.Significance. Results obtained on phantom data showed that the virtual 4DCT method was accurate, allowing its application on patient data for testing within a clinical scenario.

Determination of ion recombination and polarity effects for the PTW Advanced Markus ionization chamber in synchrotron based scanned proton and carbon ion beams.

The aim of this work was the investigation of the ion recombination and polarity factors (ksat ad kpol) for a PTW Advanced Markus ionization chamber exposed to proton and carbon ion beams at the Centro Nazionale di Adroterapia Oncologica. Measurements with protons were specifically dedicated for ocular treatments, in the low energy range and for small, collimated scanning fields. For both protons and carbon ions, several measurements were performed by delivering a 2D single energy layer of 3x3 cm2 and homogeneous, biologically-optimized SOBPs. Data were collected at different depths in water, by varying the voltage values of the ionization chamber and for two different dose rates (the nominal one and one reduced to 20% of it). The ksat-values were determined from extrapolation of the saturation curves. Furthermore kpol-values were calculated using the recommendations from the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice. Results showed that the Advanced Markus performs optimally in this clinical scenario characterized by small treatment volumes and high dose gradients although for both particle types, but particularly for carbon ions, a charge multiplication effect up to 1.7% occurs at voltage higher than 150 V. For protons, both the ion recombination and polarity corrections were always smaller than 0.3%, for all the analysed cases and adopted dose rates, so not affecting the dosimetric measurements for clinical routine. For carbon ions the polarity effect can be neglected while ion recombination has to be carefully calculated and cannot be neglected since corrections even higher than 1% can be found, especially at high LET measuring points.

Emergence of an Ising critical regime in the clustering of one-dimensional soft matter revealed through string variables.

Soft matter systems are renowned for being able to display complex emerging phenomena such as clustering phases. Recently, a surprising quantum phase transition has been revealed in a one-dimensional (1D) system composed of bosons interacting via a pairwise soft potential in the continuum. It was shown that the spatial coordinates undergoing two-particle clustering could be mapped into quantum spin variables of a 1D transverse Ising model. In this work we investigate the manifestation of an analogous critical phenomenon in 1D classical fluids of soft particles in the continuum. In particular, we study the low-temperature behavior of three different classical models of 1D soft matter, whose interparticle interactions allow for clustering. The same string variables highlight that, at the commensurate density for the two-particle cluster phase, the peculiar pairing of neighboring soft particles can be nontrivially mapped onto a 1D discrete classical Ising model. We also observe a related phenomenon, namely the presence of an anomalous peak in the low-temperature specific heat, thus indicating the emergence of Schottky phenomenology in a nonmagnetic fluid.

Reirradiation of salivary gland tumors with carbon ion radiotherapy at CNAO.

AIMS: To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. METHODS: From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. RESULTS: Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. CONCLUSIONS: CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

Carbon ions therapy as single treatment in chordoma of the sacrum. Histologic and metabolic outcome studies.

OBJECTIVE: Even though carbon ions treatment (CIRT) of sacral chordoma (SC) substantially reduces tumor mass, tumor remnants are observed in most patients. Differentiating tumor remnants from necrosis is challenging, expensive in terms of imaging and time-consuming. So far, there has not been a systematic histological and metabolic analysis of post-CIRT lesions. We designed a prospective study aiming to histologically a metabolically differentiate between viable tumor and foci of necrosis and of fibrosclerosis after CIRT and correlate these findings to clinical outcome in patients with SC. PATIENTS AND METHODS: Between January 2013 and December 2016 18 patients, 12 males and 6 females, with histological confirmation of sacral chordoma, underwent CIRT. The total dose was 70.4 GyE, with a daily fraction of 4.4 GyE, for 4 weeks. MRI was performed every three months after treatment. FDG PET-CT scan and CT-guided needle biopsy were performed 6-12 months after CIRT. The incidence of complications (intraoperative and postoperative), local control (LC), overall survival (OS) and progression-free survival (PFS), changes in neurological status, clinical outcomes and toxicity were considered. RESULTS: All histological analysis but 2 reported signs of necrosis and of fibrosclerosis after CIRT. One of these 2 patients turned into a dedifferentiated chordoma. Radiological partial response (PR) was observed in 10 patients (56.3%) and stable disease (SD) in 5 patients (28.3). Two patients (11%) had a local relapse. The overall survival rate was 100% at 24 months. FDG PET CT after CIRT showed uptake decreasing compared with the baseline exam in all but one patient. CONCLUSIONS: The histological presence of necrosis and of fibrosclerosis after CIRT at the histological analysis supports the previous clinical evidence on the efficacy of CIRT. Volumetric stability of the residual mass should be considered as a success of treatment. In cases of a volumetric increase of the mass, a CT needle biopsy should always be performed. In our series, during the follow-up, the FDG-PET was able to promptly detect an increased uptake in the case which later was histologically defined as dedifferentiated chordoma.

RIDOS: A new system for online computation of the delivered dose distributions in scanning ion beam therapy.

PURPOSE: To describe a new system for scanned ion beam therapy, named RIDOS (Real-time Ion DOse planning and delivery System), which performs real time delivered dose verification integrating the information from a clinical beam monitoring system with a Graphic Processing Unit (GPU) based dose calculation in patient Computed Tomography. METHODS: A benchmarked dose computation algorithm for scanned ion beams has been parallelized and adapted to run on a GPU architecture. A workstation equipped with a NVIDIA GPU has been interfaced through a National Instruments PXI-crate with the dose delivery system of the Italian National Center of Oncological Hadrontherapy (CNAO) to receive in real-time the measured beam parameters. Data from a patient monitoring system are also collected to associate the respiratory phases with each spot during the delivery of the dose. Using both measured and planned spot properties, RIDOS evaluates during the few seconds of inter-spill time the cumulative delivered and prescribed dose distributions and compares them through a fast γ-index algorithm. RESULTS: The accuracy of the GPU-based algorithms was assessed against the CPU-based ones and the differences were found below 1‰. The cumulative planned and delivered doses are computed at the end of each spill in about 300 ms, while the dose comparison takes approximatively 400 ms. The whole operation provides the results before the next spill starts. CONCLUSIONS: RIDOS system is able to provide a fast computation of the delivered dose in the inter-spill time of the CNAO facility and allows to monitor online the dose deposition accuracy all along the treatment.

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.

A COMPARISON BETWEEN X-RAY AND CARBON ION IRRADIATION IN HUMAN NEURAL STEM CELLS.

Glioblastoma multiforme (GBM) is characterized by a poor prognosis and a median survival of ~12-18 months. GBM is usually managed by neurosurgery followed by both chemotherapy and radiotherapy. Since GBM develops resistance to conventional therapies, treatment with C-ions is promising to completely eradicate the tumoural mass. During cranial irradiation, exposure of healthy tissues is inevitable. Because of the presence of neural stem cells, a deep investigation on the effects of C-ion irradiation with respect to X-ray induced damage is mandatory to allow a better definition of treatments. In this work, the comparison of X-rays and C-ion irradiation-induced effects on human neural stem cell, focusing on multiple endpoints, such as cell viability, cytokine secretion and spheroid formation is presented. Results show different temporal and dose responses of human neural stem cells to the different radiation qualities, suggesting different underpinning mechanisms of radiation-induced damages.

Dosimetric characterization of carbon fiber stabilization devices for post-operative particle therapy.

PURPOSE: The aim of this study was to evaluate the dosimetric impact caused by recently introduced carbon fiber reinforced polyetheretherketone (CF/PEEK) stabilization devices, in comparison with conventional titanium (Ti) implants, for post-operative particle therapy (PT). METHODS: As a first step, protons and carbon ions Spread-Out Bragg Peaks (SOBPs) were delivered to CF/PEEK and Ti screws. Transversal dose profiles were acquired with EBT3 films to evaluate beam perturbation. Effects on image quality and reconstruction artifacts were then investigated. CT scans of CF/PEEK and Ti implants were acquired according to our clinical protocol and Hounsfield Unit (HU) mean values were evaluated in three regions of interest. Implants and artifacts were then contoured in the sample CT scans, together with a target volume to simulate a spine tumor. Dose calculation accuracy was assessed by comparing optimized dose distributions with Monte Carlo simulations. In the end, the treatment plans of nine real patients (seven with CF/PEEK and two with Ti stabilization devices) were retrospectively analyzed to evaluate the dosimetric impact potentially occurring if improper management of the spine implant was carried out. RESULTS: As expected, CF/PEEK screw caused a very slight beam perturbation in comparison with Ti ones, leading to a lower degree of dose degradation in case of contouring and/or set-up uncertainties. Furthermore, CF/PEEK devices did not determine appreciable HU artifacts on CT images thus improving image quality and, as a final result, dose calculation accuracy. CONCLUSIONS: CF/PEEK spinal fixation devices resulted dosimetrically more suitable than commonly-used Ti implants for post-operative PT.

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.

Optimizing the modified microdosimetric kinetic model input parameters for proton and 4He ion beam therapy application.

Models able to predict relative biological effectiveness (RBE) values are necessary for an accurate determination of the biological effect with proton and 4He ion beams. This is particularly important when including RBE calculations in treatment planning studies comparing biologically optimized proton and 4He ion beam plans. In this work, we have tailored the predictions of the modified microdosimetric kinetic model (MKM), which is clinically applied for carbon ion beam therapy in Japan, to reproduce RBE with proton and 4He ion beams. We have tuned the input parameters of the MKM, i.e. the domain and nucleus radii, reproducing an experimental database of initial RBE data for proton and He ion beams. The modified MKM, with the best fit parameters obtained, has been used to reproduce in vitro cell survival data in clinically-relevant scenarios. A satisfactory agreement has been found for the studied cell lines, A549 and RENCA, with the mean absolute survival variation between the data and predictions within 2% and 5% for proton and 4He ion beams, respectively. Moreover, a sensitivity study has been performed varying the domain and nucleus radii and the quadratic parameter of the photon response curve. The promising agreement found in this work for the studied clinical-like scenarios supports the usage of the modified MKM for treatment planning studies in proton and 4He ion beam therapy.

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.

Characterization of a commercial scintillation detector for 2-D dosimetry in scanned proton and carbon ion beams.

INTRODUCTION: Pencil beam scanning technique used at CNAO requires beam characteristics to be carefully assessed and periodically checked to guarantee patient safety. This study aimed at characterizing the Lynx® detector (IBA Dosimetry) for commissioning and periodic quality assurance (QA) for proton and carbon ion beams, as compared to EBT3 films, currently used for QA checks. METHODS AND MATERIALS: The Lynx® is a 2-D high-resolution dosimetry system consisting of a scintillating screen coupled with a CCD camera, in a compact light-tight box. The scintillator was preliminarily characterized in terms of short-term stability, linearity with number of particles, image quality and response dependence on iris setting and beam current; Lynx® was then systematically tested against EBT3 films. The detector response dependence on radiation LET was also assessed. RESULTS: Preliminary results have shown that Lynx is suitable to be used for commissioning and QA checks for proton and carbon ion scanning beams; the cross-check with EBT3 films showed a good agreement between the two detectors, for both single spot and scanned field measurements. The strong LET dependence of the scintillator due to quenching effect makes Lynx® suitable only for relative 2-D dosimetry measurements. CONCLUSION: Lynx® appears as a promising tool for commissioning and periodic QA checks for both protons and carbon ion beams. This detector can be used as an alternative of EBT3 films, allowing real-time measurements and analysis, with a significant time sparing.

Quality assurance of carbon ion and proton beams: A feasibility study for using the 2D MatriXX detector.

PURPOSE: The quality assurance (QA) procedures in particle therapy centers with active beam scanning make extensive use of films, which do not provide immediate results. The purpose of this work is to verify whether the 2D MatriXX detector by IBA Dosimetry has enough sensitivity to replace films in some of the measurements. METHODS: MatriXX is a commercial detector composed of 32×32 parallel plate ionization chambers designed for pre-treatment dose verification in conventional radiation therapy. The detector and GAFCHROMIC® films were exposed simultaneously to a 131.44MeV proton and a 221.45MeV/u carbon-ion therapeutic beam at the CNAO therapy center of Pavia - Italy, and the results were analyzed and compared. RESULTS: The sensitivity MatriXX on the beam position, beam width and field flatness was investigated. For the first two quantities, a method for correcting systematic uncertainties, dependent on the beam size, was developed allowing to achieve a position resolution equal to 230µm for carbon ions and less than 100µm for protons. The beam size and the field flatness measured using MatriXX were compared with the same quantities measured with the irradiated film, showing a good agreement. CONCLUSIONS: The results indicate that a 2D detector such as MatriXX can be used to measure several parameters of a scanned ion beam quickly and precisely and suggest that the QA would benefit from a new protocol where the MatriXX detector is added to the existing systems.

A novel algorithm for the calculation of physical and biological irradiation quantities in scanned ion beam therapy: the beamlet superposition approach.

The calculation algorithm of a modern treatment planning system for ion-beam radiotherapy should ideally be able to deal with different ion species (e.g. protons and carbon ions), to provide relative biological effectiveness (RBE) evaluations and to describe different beam lines. In this work we propose a new approach for ion irradiation outcomes computations, the beamlet superposition (BS) model, which satisfies these requirements. This model applies and extends the concepts of previous fluence-weighted pencil-beam algorithms to quantities of radiobiological interest other than dose, i.e. RBE- and LET-related quantities. It describes an ion beam through a beam-line specific, weighted superposition of universal beamlets. The universal physical and radiobiological irradiation effect of the beamlets on a representative set of water-like tissues is evaluated once, coupling the per-track information derived from FLUKA Monte Carlo simulations with the radiobiological effectiveness provided by the microdosimetric kinetic model and the local effect model. Thanks to an extension of the superposition concept, the beamlet irradiation action superposition is applicable for the evaluation of dose, RBE and LET distributions. The weight function for the beamlets superposition is derived from the beam phase space density at the patient entrance. A general beam model commissioning procedure is proposed, which has successfully been tested on the CNAO beam line. The BS model provides the evaluation of different irradiation quantities for different ions, the adaptability permitted by weight functions and the evaluation speed of analitical approaches. Benchmarking plans in simple geometries and clinical plans are shown to demonstrate the model capabilities.

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.

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.