Rapid effective dose calculation for raster-scanning 4He ion therapy with the modified microdosimetric kinetic model (mMKM).

PURPOSE: To develop and verify effective dose (DRBE) calculation in 4He ion beam therapy based on the modified microdosimetric kinetic model (mMKM) and evaluate the bio-sensitivity of mMKM-based plans to clinical parameters using a fast analytical dose engine. METHODS: Mixed radiation field particle spectra (MRFS) databases have been generated with Monte-Carlo (MC) simulations for 4He-ion beams. Relative biological effectiveness (RBE) and DRBE calculation using MRFS were established within a fast analytical engine. Spread-out Bragg-Peaks (SOBPs) in water were optimized for two dose levels and two tissue types with photon linear-quadratic model parameters αph, ßph, and (α/ß)ph to verify MRFS-derived database implementation against computations with MC-generated mixed-field α and ß databases. Bio-sensitivity of the SOBPs was investigated by varying absolute values of ßph, while keeping (α/ß)ph constant. Additionally, dose, dose-averaged linear energy transfer, and bio-sensitivity were investigated for two patient cases. RESULTS: Using MRFS-derived databases, dose differences ≲2% in the plateau and SOBP are observed compared to computations with MC-generated databases. Bio-sensitivity studies show larger deviations when altering the absolute ßph value, with maximum D50% changes of ~5%, with similar results for patient cases. Bio-sensitivity analysis indicates a greater impact on DRBE varying (α/ß)ph than ßph in mMKM. CONCLUSIONS: The MRSF approach yielded negligible differences in the target and small differences in the plateau compared to MC-generated databases. The presented analyses provide guidance for proper implementation of RBE-weighted 4He ion dose prescription and planning with mMKM. The MRFS-DRBE calculation approach using mMKM will be implemented in a clinical treatment planning system.

[Construction of radiobiological models as TCP (tumor control probability) and NTCP (normal tissue complication probability): from dose to clinical effects prediction]. / Construction des modèles radiobiologiques de type TCP (tumor control probability) et NTCP (normal tissue complication probability) : de la dose à la prédiction des effets cliniques.

In radiotherapy, the dose prescription is currently based on discretized dose-effects records that do not take into fully account for the complexity of the patient-dose-response relationship. Their predictive performance on both anti-tumour efficacy and toxicity can be optimized by integrating radiobiological models. It is with this in mind that the calculation models TCP (Tumor Control Probability) and NTCP (Normal Tissue Complication Probability) have been developed. Their construction involves several important steps that are necessary and important to understand. The first step is based on radiobiological models allowing to calculate according to more or less complexity the rate of surviving cells after irradiation. Two additional steps are required to convert the physical dose into an equivalent biological dose, in particular a 2Gy equivalent biological dose (EQD2): first to take into account the effect of the fractionation of the dose for both the target volume and the organs at risk; second to convert an heterogeneous dose to an organ into an homogeneous dose having the same effect (Niemierko generalized equivalent uniform dose (gEUD)). Finally, the process of predicting clinical effects based on radiobiological models transform doses into tumour control (TCP) or toxicity (NTCP) probabilities using parameters that reflect the radiobiological characteristics of the tissues in question. The use of these models in current practice is still limited, but since the radiotherapy softwares increasingly integrate them, it is important to know the principle and limits of application of these models.

Offline imaging of positron emitters induced by therapeutic helium, carbon and oxygen ion beams with a full-ring PET/CT scanner: experiments in reference targets.

In vivo verification of light ion therapy based on positron-emission tomography (PET) imaging of irradiation induced patient activation relies on activity predictions from Monte-Carlo (MC) or analytical computational engines for comparison to the measurements. In order to achieve the necessary accuracy, experimental data are indispensable for the validation of the calculation models. For this we irradiated thick reference targets with mono-energetic helium, carbon and oxygen ion beams and measured the resulting material activation offline with a commercial full-ring PET/CT scanner located nearby the treatment room. Acquired PET data were analysed over time to separate the activity contribution of different radionuclides. Determined production yields were compared to published findings obtained from in-beam activation measurements with a limited-angle double-head PET camera. In addition, we investigated the time-dependence of the measured radionuclide-specific contributions and of the distal activity range, as well as the lateral spread of the activity signal as a function of beam penetration depth. We present radionuclide-specific depth-resolved activity distributions and production yields for the radionuclides [Formula: see text], [Formula: see text] and [Formula: see text], dominating irradiation-induced patient activation. We observe systematically lower production yields with a ratio between the dual-head and our full-ring PET measurements of, on average, 1.7 and 1.3 for the oxygen and carbon beam irradiations, and 1.7 (2.1) for the high (low) energy helium beam irradiations. Findings on the temporal development of the activity range confirm the expectation, with the oxygen beam induced signal being the most sensitive scenario. The experimental data reported in this work, acquired with a state-of-the-art full ring PET scanner, provide a comprehensive and consistent basis for the benchmarking of PET signal calculation engines. In particular, they can support a fine-tuning of the underlying physics models used by the respective implementation and therefore improve the accuracy of PET-based therapy verifications at current and future treatment facilities.

[Proton therapy for head and neck squamous cell carcinomas: From physics to clinic]. / Protonthérapie des carcinomes épidermoïdes des voies aérodigestives supérieures : de la physique à la clinique.

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.

An overview of recent developments in FLUKA PET tools.

The new developments of the FLUKA Positron-Emission-Tomography (PET) tools are detailed. FLUKA is a fully integrated Monte Carlo (MC) particle transport code, used for an extended range of applications, including Medical Physics. Recently, it provided the medical community with dedicated simulation tools for clinical applications, including the PET simulation package. PET is a well-established imaging technique in nuclear medicine, and a promising method for clinical in vivo treatment verification in hadrontherapy. The application of clinically established PET scanners to new irradiation environments such as hadrontherapy requires further experimental and theoretical research to which MC simulations could be applied. The FLUKA PET tools, besides featuring PET scanner models in its library, allow the configuration of new PET prototypes via the FLUKA Graphical User Interface (GUI) Flair. Both the beam time structure and scan time can be specified by the user, reproducing PET acquisitions in time, in a particle therapy scenario. Furthermore, different scoring routines allow the analysis of single and coincident events, and identification of parent isotopes generating annihilation events. Two reconstruction codes are currently supported: the Filtered Back-Projection (FBP) and Maximum-Likelihood Expectation Maximization (MLEM), the latter embedded in the tools. Compatibility with other reconstruction frameworks is also possible. The FLUKA PET tools package has been successfully tested for different detectors and scenarios, including conventional functional PET applications and in beam PET, either using radioactive sources, or simulating hadron beam irradiations. The results obtained so far confirm the FLUKA PET tools suitability to perform PET simulations in R&D environment.

Helium ions at the heidelberg ion beam therapy center: comparisons between FLUKA Monte Carlo code predictions and dosimetric measurements.

In the field of particle therapy helium ion beams could offer an alternative for radiotherapy treatments, owing to their interesting physical and biological properties intermediate between protons and carbon ions. We present in this work the comparisons and validations of the Monte Carlo FLUKA code against in-depth dosimetric measurements acquired at the Heidelberg Ion Beam Therapy Center (HIT). Depth dose distributions in water with and without ripple filter, lateral profiles at different depths in water and a spread-out Bragg peak were investigated. After experimentally-driven tuning of the less known initial beam characteristics in vacuum (beam lateral size and momentum spread) and simulation parameters (water ionization potential), comparisons of depth dose distributions were performed between simulations and measurements, which showed overall good agreement with range differences below 0.1 mm and dose-weighted average dose-differences below 2.3% throughout the entire energy range. Comparisons of lateral dose profiles showed differences in full-width-half-maximum lower than 0.7 mm. Measurements of the spread-out Bragg peak indicated differences with simulations below 1% in the high dose regions and 3% in all other regions, with a range difference less than 0.5 mm. Despite the promising results, some discrepancies between simulations and measurements were observed, particularly at high energies. These differences were attributed to an underestimation of dose contributions from secondary particles at large angles, as seen in a triple Gaussian parametrization of the lateral profiles along the depth. However, the results allowed us to validate FLUKA simulations against measurements, confirming its suitability for 4He ion beam modeling in preparation of clinical establishment at HIT. Future activities building on this work will include treatment plan comparisons using validated biological models between proton and helium ions, either within a Monte Carlo treatment planning engine based on the same FLUKA code, or an independent analytical planning system fed with a validated database of inputs calculated with FLUKA.

Dosimetric verification in water of a Monte Carlo treatment planning tool for proton, helium, carbon and oxygen ion beams at the Heidelberg Ion Beam Therapy Center.

The introduction of 'new' ion species in particle therapy needs to be supported by a thorough assessment of their dosimetric properties and by treatment planning comparisons with clinically used proton and carbon ion beams. In addition to the latter two ions, helium and oxygen ion beams are foreseen at the Heidelberg Ion Beam Therapy Center (HIT) as potential assets for improving clinical outcomes in the near future. We present in this study a dosimetric validation of a FLUKA-based Monte Carlo treatment planning tool (MCTP) for protons, helium, carbon and oxygen ions for spread-out Bragg peaks in water. The comparisons between the ions show the dosimetric advantages of helium and heavier ion beams in terms of their distal and lateral fall-offs with respect to protons, reducing the lateral size of the region receiving 50% of the planned dose up to 12 mm. However, carbon and oxygen ions showed significant doses beyond the target due to the higher fragmentation tail compared to lighter ions (p and He), up to 25%. The Monte Carlo predictions were found to be in excellent geometrical agreement with the measurements, with deviations below 1 mm for all parameters investigated such as target and lateral size as well as distal fall-offs. Measured and simulated absolute dose values agreed within about 2.5% on the overall dose distributions. The MCTP tool, which supports the usage of multiple state-of-the-art relative biological effectiveness models, will provide a solid engine for treatment planning comparisons at HIT.

Experimental dosimetric comparison of 1H, 4He, 12C and 16O scanned ion beams.

At the Heidelberg Ion Beam Therapy Center, scanned helium and oxygen ion beams are available in addition to the clinically used protons and carbon ions for physical and biological experiments. In this work, a study of the basic dosimetric features of the different ions is performed in the entire therapeutic energy range. Depth dose distributions are investigated for pencil-like beam irradiation, with and without a modulating ripple filter, focusing on the extraction of key Bragg curve parameters, such as the range, the peak-width and the distal 80%-20% fall-off. Pencil-beam lateral profiles are measured at different depths in water, and parameterized with multiple Gaussian functions. A more complex situation of an extended treatment field is analyzed through a physically optimized spread-out Bragg peak, delivered with beam scanning. The experimental results of this physical beam characterization indicate that helium ions could afford a more conformal treatment and in turn, increased tumor control. This is mainly due to a smaller lateral scattering than with protons, leading to better lateral and distal fall-off, as well as a lower fragmentation tail compared to carbon and oxygen ions. Moreover, the dosimetric dataset can be used directly for comparison with results from analytical dose engines or Monte Carlo codes. Specifically, it was used at the Heidelberg Ion Beam Therapy Center to generate a new input database for a research analytical treatment planning system, as well as for validation of a general purpose Monte Carlo program, in order to lay the groundwork for biological experiments and further patient planning studies.

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.

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.

First in situ TOF-PET study using digital photon counters for proton range verification.

Positron emission tomography (PET) is the imaging modality most extensively tested for treatment monitoring in particle therapy. Optimal use of PET in proton therapy requires in situ acquisition of the relatively strong (15)O signal due to its relatively short half-life (~2 min) and high oxygen content in biological tissues, enabling shorter scans that are less sensitive to biological washout. This paper presents the first performance tests of a scaled-down in situ time-of-flight (TOF) PET system based on digital photon counters (DPCs) coupled to Cerium-doped Lutetium Yttrium Silicate (LYSO:Ce) crystals, providing quantitative results representative of a dual-head tomograph that complies with spatial constraints typically encountered in clinical practice (2 × 50°, of 360°, transaxial angular acceptance). The proton-induced activity inside polymethylmethacrylate (PMMA) and polyethylene (PE) phantoms was acquired within beam pauses (in-beam) and immediately after irradiation by an actively-delivered synchrotron pencil-beam, with clinically relevant 125.67 MeV/u, 4.6 × 10(8) protons s(-1), and 10(10) total protons. 3D activity maps reconstructed with and without TOF information are compared to FLUKA simulations, demonstrating the benefit of TOF-PET to reduce limited-angle artefacts using a 382 ps full width at half maximum coincidence resolving time. The time-dependent contributions from different radionuclides to the total count-rate are investigated. We furthermore study the impact of the acquisition time window on the laterally integrated activity depth-profiles, with emphasis on 2 min acquisitions starting at different time points. The results depend on phantom composition and reflect the differences in relative contributions from the radionuclides originating from carbon and oxygen. We observe very good agreement between the shapes of the simulated and measured activity depth-profiles for post-beam protocols. However, our results also suggest that available experimental cross sections underestimate the production of (10)C for in-beam acquisitions, which in PE results in an overestimation of the predicted activity range by 1.4 mm. The uncertainty in the activity range measured in PMMA using the DPC-based TOF-PET prototype setup equals 0.2 mm-0.3 mm.

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.

Data-driven RBE parameterization for helium ion beams.

Helium ion beams are expected to be available again in the near future for clinical use. A suitable formalism to obtain relative biological effectiveness (RBE) values for treatment planning (TP) studies is needed. In this work we developed a data-driven RBE parameterization based on published in vitro experimental values. The RBE parameterization has been developed within the framework of the linear-quadratic (LQ) model as a function of the helium linear energy transfer (LET), dose and the tissue specific parameter (α/ß)ph of the LQ model for the reference radiation. Analytic expressions are provided, derived from the collected database, describing the RBEα = αHe/αph and Rß = ßHe/ßph ratios as a function of LET. Calculated RBE values at 2 Gy photon dose and at 10% survival (RBE10) are compared with the experimental ones. Pearson's correlation coefficients were, respectively, 0.85 and 0.84 confirming the soundness of the introduced approach. Moreover, due to the lack of experimental data at low LET, clonogenic experiments have been performed irradiating A549 cell line with (α/ß)ph = 5.4 Gy at the entrance of a 56.4 MeV u(-1)He beam at the Heidelberg Ion Beam Therapy Center. The proposed parameterization reproduces the measured cell survival within the experimental uncertainties. A RBE formula, which depends only on dose, LET and (α/ß)ph as input parameters is proposed, allowing a straightforward implementation in a TP system.

A model for the accurate computation of the lateral scattering of protons in water.

A pencil beam model for the calculation of the lateral scattering in water of protons for any therapeutic energy and depth is presented. It is based on the full Molière theory, taking into account the energy loss and the effects of mixtures and compounds. Concerning the electromagnetic part, the model has no free parameters and is in very good agreement with the FLUKA Monte Carlo (MC) code. The effects of the nuclear interactions are parametrized with a two-parameter tail function, adjusted on MC data calculated with FLUKA. The model, after the convolution with the beam and the detector response, is in agreement with recent proton data in water from HIT. The model gives results with the same accuracy of the MC codes based on Molière theory, with a much shorter computing time.

Integration and evaluation of automated Monte Carlo simulations in the clinical practice of scanned proton and carbon ion beam therapy.

Monte Carlo (MC) simulations of beam interaction and transport in matter are increasingly considered as essential tools to support several aspects of radiation therapy. Despite the vast application of MC to photon therapy and scattered proton therapy, clinical experience in scanned ion beam therapy is still scarce. This is especially the case for ions heavier than protons, which pose additional issues like nuclear fragmentation and varying biological effectiveness. In this work, we present the evaluation of a dedicated framework which has been developed at the Heidelberg Ion Beam Therapy Center to provide automated FLUKA MC simulations of clinical patient treatments with scanned proton and carbon ion beams. Investigations on the number of transported primaries and the dimension of the geometry and scoring grids have been performed for a representative class of patient cases in order to provide recommendations on the simulation settings, showing that recommendations derived from the experience in proton therapy cannot be directly translated to the case of carbon ion beams. The MC results with the optimized settings have been compared to the calculations of the analytical treatment planning system (TPS), showing that regardless of the consistency of the two systems (in terms of beam model in water and range calculation in different materials) relevant differences can be found in dosimetric quantities and range, especially in the case of heterogeneous and deep seated treatment sites depending on the ion beam species and energies, homogeneity of the traversed tissue and size of the treated volume. The analysis of typical TPS speed-up approximations highlighted effects which deserve accurate treatment, in contrast to adequate beam model simplifications for scanned ion beam therapy. In terms of biological dose calculations, the investigation of the mixed field components in realistic anatomical situations confirmed the findings of previous groups so far reported only in homogenous water targets. This work can thus be useful to other centers commencing clinical experience in scanned ion beam therapy.

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.

A Monte Carlo-based treatment planning tool for proton therapy.

In the field of radiotherapy, Monte Carlo (MC) particle transport calculations are recognized for their superior accuracy in predicting dose and fluence distributions in patient geometries compared to analytical algorithms which are generally used for treatment planning due to their shorter execution times. In this work, a newly developed MC-based treatment planning (MCTP) tool for proton therapy is proposed to support treatment planning studies and research applications. It allows for single-field and simultaneous multiple-field optimization in realistic treatment scenarios and is based on the MC code FLUKA. Relative biological effectiveness (RBE)-weighted dose is optimized either with the common approach using a constant RBE of 1.1 or using a variable RBE according to radiobiological input tables. A validated reimplementation of the local effect model was used in this work to generate radiobiological input tables. Examples of treatment plans in water phantoms and in patient-CT geometries together with an experimental dosimetric validation of the plans are presented for clinical treatment parameters as used at the Italian National Center for Oncological Hadron Therapy. To conclude, a versatile MCTP tool for proton therapy was developed and validated for realistic patient treatment scenarios against dosimetric measurements and commercial analytical TP calculations. It is aimed to be used in future for research and to support treatment planning at state-of-the-art ion beam therapy facilities.