G. Magro

The FLUKA Code: An Accurate Simulation Tool for Particle Therapy

Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved. In addition, accurate prediction of emerging secondary radiation is of utmost importance in innovative areas of research aiming at in vivo treatment verification. This contribution will address the recent developments of the FLUKA MC code and its practical applications in this field. Refinements of the FLUKA nuclear models in the therapeutic energy interval lead to an improved description of the mixed radiation field as shown in the presented benchmarks against experimental data with both 4He and 12C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth–dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features.

Biologically optimized helium ion plans: calculation approach and its in vitro validation

Treatment planning studies on the biological effect of raster-scanned helium ion beams should be performed, together with their experimental verification, before their clinical application at the Heidelberg Ion Beam Therapy Center (HIT). For this purpose, we introduce a novel calculation approach based on integrating data-driven biological models in our Monte Carlo treatment planning (MCTP) tool. Dealing with a mixed radiation field, the biological effect of the primary (4)He ion beams, of the secondary (3)He and (4)He (Z  =  2) fragments and of the produced protons, deuterons and tritons (Z  =  1) has to be taken into account. A spread-out Bragg peak (SOBP) in water, representative of a clinically-relevant scenario, has been biologically optimized with the MCTP and then delivered at HIT. Predictions of cell survival and RBE for a tumor cell line, characterized by [Formula: see text] Gy, have been successfully compared against measured clonogenic survival data. The mean absolute survival variation ([Formula: see text]) between model predictions and experimental data was 5.3%  ±  0.9%. A sensitivity study, i.e. quantifying the variation of the estimations for the studied plan as a function of the applied phenomenological modelling approach, has been performed. The feasibility of a simpler biological modelling based on dose-averaged LET (linear energy transfer) has been tested. Moreover, comparisons with biophysical models such as the local effect model (LEM) and the repair-misrepair-fixation (RMF) model were performed. [Formula: see text] values for the LEM and the RMF model were, respectively, 4.5%  ±  0.8% and 5.8%  ±  1.1%. The satisfactorily agreement found in this work for the studied SOBP, representative of clinically-relevant scenario, suggests that the introduced approach could be applied for an accurate estimation of the biological effect for helium ion radiotherapy.

Dose prescription in carbon ion radiotherapy: How to compare two different RBE-weighted dose calculation systems.

BACKGROUND AND PURPOSE In carbon ion radiotherapy (CIRT), the use of different relative biological effectiveness (RBE) models in the RBE-weighted dose (DRBE) calculation can lead to deviations in the physical dose (Dphy) delivered to the patient. Our aim is to reduce target Dphy deviations by converting prescription dose values. MATERIAL AND METHODS Planning data of patients treated at the National Institute of Radiological Sciences (NIRS) were collected, with prescribed doses per fraction ranging from 3.6Gy (RBE) to 4.6Gy (RBE), according to the Japanese semi-empirical model. The Dphy was Monte Carlo (MC) re-calculated simulating the NIRS beamline. The local effect model (LEM)_I was then applied to estimate DRBE. Target median DRBE ratios between MC+LEM_I and NIRS plans determined correction factors for the conversion of prescription doses. Plans were re-optimized in a LEM_I-based commercial system, prescribing the NIRS uncorrected and corrected DRBE. RESULTS The MC+LEM_I target median DRBE was respectively 15% and 5% higher than the NIRS reference, for the lowest and highest dose levels. Uncorrected DRBE prescription resulted in significantly lower target Dphy in re-optimized plans, with respect to NIRS plans. CONCLUSIONS Prescription dose conversion factors could minimize target physical dose variations due to the use of different radiobiological models in the calculation of CIRT RBE-weighted dose.

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.

Commissioning of the 4-D treatment delivery system for organ motion management in synchrotron-based scanning ion beams

PURPOSE The aim of this work was the commissioning of delivery procedures for the treatment of moving targets in scanning pencil beam hadrontherapy. METHODS EBT3 films fixed to the Anzai Respiratory Phantom were exposed to carbon ion scanned homogeneous fields (E=332MeV/u). To evaluate the interplay effect, field size and flatness for 3 different scenarios were compared to static condition: gated irradiation or repainting alone and combination of both. Respiratory signal was provided by Anzai pressure sensor or optical tracking system (OTS). End-exhale phase and 1s gating window were chosen (2.5mm residual motion). Dose measurements were performed using a PinPoint ionization chamber inserted into the Brainlab ET Gating Phantom. A sub-set of tests was also performed using proton beams. RESULTS The combination of gating technique and repainting (N=5) showed excellent results (6.1% vs 4.3% flatness, identical field size and dose deviation within 1.3%). Treatment delivery time was acceptable. Dose homogeneity for gated irradiation alone was poor. Both Anzai sensor and OTS appeared suitable for providing respiratory signal. Comparisons between protons and carbon ions showed that larger beam spot sizes represent more favorable condition for minimizing motion effect. CONCLUSION Results of measurements performed on different phantoms showed that the combination of gating and layered repainting is suitable to treat moving targets using scanning ion beams. Abdominal compression using thermoplastic masks, together with multi-field planning approach and multi-fractionation, have also been assessed as additional strategies to mitigate the effect of patient respiration in the clinical practice.

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.

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.

Sensitivity study of the microdosimetric kinetic model parameters for carbon ion radiotherapy

In carbon ion therapy treatment planning, the relative biological effectiveness (RBE) is accounted for by optimization of the RBE-weighted dose (biological dose). The RBE calculation methods currently applied clinically in carbon ion therapy are derived from the microdosimetric kinetic model (MKM) in Japan and the local effect model (LEM) in Europe. The input parameters of these models are based on fit to experimental data subjected to uncertainties. We therefore performed a sensitivity study of the MKM input parameters, i.e. the domain radius (r d ), the nucleus radius (R n ) and the parameters of the linear quadratic (LQ) model (α x and β). The study was performed with the FLUKA Monte Carlo code, using spread out Bragg peak (SOBP) scenarios in water and a biological dose distribution in a clinical patient case. Comparisons were done between biological doses estimated applying the MKM with parameters based on HSG cells, and with HSG parameters varied separately by  ±{5, 25, 50}%. Comparisons were also done between parameter sets from different cell lines (HSG, V79, CHO and T1), as well as versions of the LEM. Of the parameters, r d had the largest impact on the biological dose distribution, especially on the absolute dose values. Increasing this parameter by 25% decreased the biological dose level at the center of a 3 Gy(RBE) SOBP by 14%. Variations in R n only influenced the biological dose distribution towards the particle range, and variations in α x resulted in minor changes in the biological dose, with an increasing impact towards the particle range. β had the overall smallest influence on the SOBPs, but the impact could become more pronounced if alternative (LET dependent) implementations are used. The resulting percentage change in the SOBPs was generally less than the percentage change in the parameters. The patient case showed similar effects as with the SOBPs in water, and parameter variations had similar impact on the biological dose when using the clinical MKM and the general MKM. The clinical LEM calculated the highest biological doses to both tumor and surrounding healthy tissues, with a median target dose (D 50%) of 40.5 Gy(RBE), while the MKM with HSG and V79 parameters resulted in a D 50% of 34.2 and 36.9 Gy(RBE), respectively. In all, the observed change in biological dose distribution due to parameter variations demonstrates the importance of accurate input parameters when applying the MKM in treatment planning.

FRoG—A New Calculation Engine for Clinical Investigations with Proton and Carbon Ion Beams at CNAO

A fast and accurate dose calculation engine for hadrontherapy is critical for both routine clinical and advanced research applications. FRoG is a graphics processing unit (GPU)-based forward calculation tool developed at CNAO (Centro Nazionale di Adroterapia Oncologica) and at HIT (Heidelberg Ion Beam Therapy Center) for fast and accurate calculation of both physical and biological dose. FRoG calculation engine adopts a triple Gaussian parameterization for the description of the lateral dose distribution. FRoG provides dose, dose-averaged linear energy transfer, and biological dose-maps, -profiles, and -volume-histograms. For the benchmark of the FRoG calculation engine, using the clinical settings available at CNAO, spread-out Bragg peaks (SOBPs) and patient cases for both proton and carbon ion beams have been calculated and compared against FLUKA Monte Carlo (MC) predictions. In addition, FRoG patient-specific quality assurance (QA) has been performed for twenty-five proton and carbon ion fields. As a result, for protons, biological dose values, using a relative biological effectiveness (RBE) of 1.1, agree on average with MC within ~1% for both SOBPs and patient plans. For carbon ions, RBE-weighted dose (DRBE) agreement against FLUKA is within ~2.5% for the studied SOBPs and patient plans. Both MKM (Microdosimetric Kinetic Model) and LEM (Local Effect Model) DRBE are implemented and tested in FRoG to support the NIRS (National Institute of Radiological Sciences)-based to LEM-based biological dose conversion. FRoG matched the measured QA dosimetric data within ~2.0% for both particle species. The typical calculation times for patients ranged from roughly 1 to 4 min for proton beams and 3 to 6 min for carbon ions on a NVIDIA® GeForce® GTX 1080 Ti. This works demonstrates FRoG’s potential to bolster clinical activity with proton and carbon ion beams at CNAO.