Welcome and Introduction Room: Salón de Actos

State of the art in ion beam therapy

• Carsten Peter Welsch (Cockcroft Institute / University of Liverpool)

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Next-generation therapy accelerators

• Yves Jongen (IBA)

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FlashTherapy: an innovation in radiation therapy

• Lucia Giuliano (INFN - National Institute for Nuclear Physics)

Room: Salón de Actos The Radiation Therapy (RT) goal is to destroy cancer cells, minimizing the damage to the rest of the body as well as any side effect. The "FLASH" Therapy, an innovative technique in radiation therapy, has shown that short pulses of electrons at very high dose rates are less harmful to healthy tissues but just as efficient as conventional dose rate radiation to inhibit tumour growth. The therapy has been successfully tested with low energy electrons in small animals. It foresees millisecond pulses of radiation (beam on time < 100-500ms) delivered at a high dose-rate (>40-100 Gy/s), over 2000 times faster and more than 1000 more intense than conventional RT. We will discuss the genesis of this methodology, the instrumentations used and its evolution.

Technical Challenges for FLASH Proton Therapy

• Simon Jolly (University College London)

Room: Salón de Actos There is growing interest in the radiotherapy community over the applications of FLASH radiotherapy, wherein the X-ray dose is delivered to the entire treatment volume in less than a second. Early pre-clinical evidence suggests that these extremely high dose rates provide significant sparing of healthy tissue compared to conventional radiotherapy without reducing the damage to cancerous cells. This interest has been reflected in the proton therapy community, with early tests indicating that the FLASH effect is also present with high dose rate proton irradiation. In order to deliver clinically relevant doses at FLASH dose rates, significant technical hurdles must be overcome before FLASH proton therapy can be realised, particularly for modern spot-scanning dose delivery. The current state of the art in clinical proton therapy technology is discussed, along with the current specification for clinical FLASH proton therapy. The technical challenges are outlined for each of the existing accelerator and beam delivery technologies, with possible routes discussed by which the technology can evolve to meet these challenges.

Exploring of advances in high gradient technologies for use in hadron therapy accelerators

• Anna Vnuchenko (Instituto de Física Corpuscular (IFIC), Valencia, Spain)

Room: Salón de Actos Research in the field of hadron therapy has led to a new perspective for radiotherapy treatment of cancer patients through the development of a linear proton accelerator based on high gradient technology. The main challenges of such a facility are the effective acceleration of low energy beams and the reduction of the facility footprint and its electricity consumption. All-linac designs for proton and light ion therapy linacs have potential advantages over existing circular facilities. Recent developments at CERN high frequency RFQs and high-gradient accelerating structures can make important contributions to linac-based facilities. High performance of these components during high power test indicates their potential. The maximum gradient and high gradient limiting factors of linacs are described.

Imaging beam in patient

• Katia Parodi (Ludwig-Maximilians-Universität München)

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PET Imaging and Dose correlation from Proton Activation.

• Victor Valladolid Onecha (Grupo de Física Nuclear, Universidad Complutense de Madrid)

Room: Salón de Actos Range verification techniques for protontherapy include positron-emission tomography (PET) and prompt-gamma (PG) imaging. The main challenges preventing their clinical implementation are, in case of PET, the relatively long half-lives of the isotopes of interest and the large energy needed to activate PET-decaying nuclei [1]. We have investigated the use of certain isotopes as contrast agents for PET, increasing their activation rates and shifting the activity peaks towards the Bragg peak. For this purpose we have developed an activation calculation tool in different software packages such as TOPAS and PenH, and we have compared both. The experiental and theoretical results show an increased PET activation at the distal end of a 150 MeV proton beam, within 1 mm from the Bragg peak (BP), using Water-18O (H2O18) as a contrast agent. The activation maps of 18F (T1/2≈110 min) and 15O (T1/2≈122 s) obtained from TOPAS and the SuperArgus 4R preclinical PET scanner [2] have been simulated with PeneloPET [3], in order to obtain 5-minute-long acquisitions right after irradiation and 15 minutes later. Results show the dominance of the 15O signal in a delocalized region far from BP in the first 5 minutes, but the BP distal end is perfectly identified for the 15 minutes delayed acquisition due to the 18F signal arising from the proton activation of 18O. The H2O18 is perfect for validation and verification with phantoms, and in vivo patients, provided if it could be biologically fixed in area of maximum dose deposition. [1] S. España, et al., “The reliability of proton-nuclear interaction cross-section data to predict proton-induced PET images in proton therapy”, Phys. Med. Biol., 56(9) 2687–2698, 2011. [2] S. España, et al., “PeneloPET, a Monte Carlo PET simulation tool based on PENELOPE: features and validation,” Phys. Med. Biol., 54 (6) 1723–1742, 2009. [3] J. M. Udías, et al., “Performance evaluation of the PET subsystem of the extended FOV SuperArgus 6R preclinical scanner,” IEEE NSS MIC, 2018.

Toward a novel treatment planning approach accounting for prompt gamma range verification

• Liheng Tian (LMU)

Room: Salón de Actos Toward a novel treatment planning approach accounting for prompt gamma range verification Introduction: Prompt gamma (PG) monitoring is widely investigated to reduce range uncertainties in proton therapy. Our previous study proposed to re-optimize the treatment plan (TP) based on spot-by-spot conformities between the PG and the dose (so called PG-dose correlation). However, a good PG-dose correlation on the planning CT could still be affected by fractional anatomical changes, for which a new approach is proposed and investigated in this study. Materials and Methods: In this work, Monte Carlo (MC) TPs are created using an extension of a research computational platform, combining MC (Geant4) pre-calculated pencil beams with the TP system (TPS) engine CERR (A computational Environment for Radiotherapy Research). Other than the previously proposed PG-dose correlation indicator, which compares the laterally integrated PG and dose profiles, a new indicator is proposed to account for the sensitivity of individual pencil beams to heterogeneities in the 3D dose distribution. This is accomplished by using a 2D distal surface derived from 3D dose distributions of single pencil beams. Combining the indicators above, new TPs are created by boosting a few pencil beams (PBs) recommended for better PG imaging. TPs are MC-recalculated on three different fractional CT scans of a head and neck and a prostate cancer patient and then compared. Advantages over other proposed methods such as spot aggregation are also investigated. Results: Re-optimized and initial TPs are comparable in terms of dose distribution and dose-averaged linear energy transfer distribution on all CTs, while the PBs boosted in the new TP maintain good PG-dose correlation in the cases of fractional anatomical changes. Comparison to the performance of the spot aggregation will be also discussed. Conclusion: Based on our previous proposal to re-optimize treatment plans using the spot-by-spot conformities of PG and dose, an improved approach is put forward to ensure enhanced robustness of the PG-dose correlation of boosted PBs in presence of interfractional anatomical changes. Acknowledgments: EU-MSCA GA n. 675265 (OMA)

The SiFi-CC project - prompt gamma imaging for real time monitoring of proton therapy

• Katarzyna Rusiecka (Marian Smoluchowski Institute of Physics, Jagiellonian University)

Room: Salón de Actos As proton therapy has become a well-established cancer treatment modality, research towards improvement of quality assurance and new treatment monitoring methods have intensified. Proton therapy offers more favorable dose deposition pattern than conventional radiotherapy, however it could be further improved if currently applied safety margins were reduced. This would be possible if methods of real time monitoring were introduced into standard clinical practice. Various real time treatment monitoring techniques based on the detection of secondary radiation have been proposed so far, with prompt gamma imaging (PGI) being one of the most promising candidates. In my presentation I will introduce the SiFi-CC project, which is a joint effort of physicists from the Jagiellonian University and the RWTH Aachen University. The aim is to develop a method for real time monitoring of dose distribution deposited during proton therapy exploiting prompt gamma radiation. For that reason, a dedicated setup is being under development, taking advantage of the latest advances in the field of scintillating detectors - heavy inorganic scintillating fibers read out by silicon photomultipliers (SiPMs). Hence the name of the collaboration - SiPMs and Fiber-based Compton Camera. The proposed detection setup will be operating in two modes: as a Compton camera (CC) and as a coded mask detector (CM). In order to optimize performance of the detector, Monte Carlo simulations of the geometry and physics performance have been carried out. Similarly, laboratory tests of various inorganic scintillators have been conducted in order to find the optimal material. The use of suitable heavy scintillating material for the active part of the detection system ensures large light output, high detection efficiency, good energy resolution and timing properties. High granularity of the proposed detector along with the fast signals and modern electronics allow for high rate capability and reduced background. The data acquisition system will be based on FPGA technology, with first stage of data processing and reduction performed on-board, which will provide high throughput, fast image reconstruction and flexibility needed for the operation of the two detection modalities.

Beam Diagnostics

• Michele Caldara (AVO/ADAM)

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Characterisation of the LHCb VELO detector modules as a non-invasive Proton Beam Monitor

• Roland Schnuerer (Cockcroft Institute)

Room: Salón de Actos In proton beam therapy, knowledge of the detailed beam properties is essential to ensure effective dose delivery to the patient. In clinical practice, currently used interceptive ionisation chambers require daily calibration and suffer from slow response time. Therefore, novel silicon-based detector technologies are developed. This contribution presents a non-invasive method for dose online monitoring. It is based on the silicon multi-strip sensor LHCb VELO (VErtex LOcator), developed originally for the LHCb experiment at CERN. The semi-circular detector geometry offers the possibility to measure beam intensity through halo measurements without interfering with the beam core. The technology has been recently tested at the MC40 proton beamline at the University of Birmingham, UK. Precise measurements of the proton beam halo were performed by synchronising the readout of the VELO detector with the RF cyclotron frequency and an in-beam ionisation chamber. Different beam sizes and beam current settings were recorded and are presented. The experimental results are compared to beam tracking simulation and summarised to characterise the VELO detector as a halo beam monitor.

Beamline characterization of a Dielectric-filled Reentrant Cavity Resonator as a Beam Current Monitor for medical cyclotron beamline at PSI, Switzerland: Its advantanges and limits

• Sudharsan Srinivasan (PSI - Paul Scherrer Institut)

Room: Salón de Actos At PSI (Paul Scherrer Institute) Villigen, Switzerland, a superconductive cyclotron called “COMET” delivers pulsed proton beam of 250MeV at 72.85MHz for proton radiation therapy. Measuring proton beam current (0.1-40 nA) is of crucial importance and is traditionally measured with invasive monitors such as ionization chambers. A new non-invasive beam current monitor working on the principle of resonance is envisaged to replace ionization chambers (due to associated scattering) and to preserve the beam quality delivered. The resonator working on its fundamental mode is tuned to the second harmonic of the pulse rate at 145.7MHz, thus providing signals proportional to beam current. The cavity resonator installed in the PROSCAN beamline of the COMET is used to measure beam current at different energies: 141, 171, 201 and 231 MeV with multiple current sweeps. This paper focuses on the signal processing chain, its noise figure evaluation and helps to identify the relationship of the resonator calibration factor as a function of beam energy. We summarize the paper with measured resonator sensitivity, its potential advantages compared to invasive beam diagnostic such as an ionization chamber and its limitation due to noise

Beam and detector characterisation using Medipix3 at MedAustron IR1 using protons and carbon ions at clinical flux rates and full energy range

• Navrit Johan Singh Bal (Nikhef National institute for subatomic physics (NL))

Room: Salón de Actos MedAustron is a synchrotron based medical accelerator using protons and carbon ions for cancer treatment, it is based near Vienna in Wiener-Neustadt, Austria. It has been operational since 2016 and it treated 193 patients in 2018. Simultaneous beam intensity and beam profile measurements over time with various beam parameters at the IR1 non-clinical research beamline have been performed with Medipix3, a single quantum counting hybrid pixel detector typically used for x-ray and electron detection. The energy range used in these measurements for protons is 62 to 800 MeV and for carbon ions is 120 to 400 MeV/A, which is the full clinical range with the addition of the experimental 800 MeV proton option intended for various research applications including proton CT. Count rate linearity was investigated using degrader plates to vary between approximately 10 and 100% of the beam intensity, resulting in count rates of up to 10$^9$ particles per second over the whole sensitive area of 28 x 28 mm$^2$. In addition, experimental low flux proton beams have been measured reducing the intensity over intermediate steps down to 10$^3$ particles per second. With and without the measurements using degrader discs, current analysis shows very high linearity (R$^2$ = 0.9995) between the expected proton fluence at 62 MeV and the integrated counts on the Medipix3 from 10$^7$ to 10$^{11}$ total counts. Average deviations of the measurements from the linear fit were found to be 2.9% without the degrader measurements and 36.2% with them. Another set of linearity measurements were performed using 800 MeV protons and degrader discs, they show high linearity (R$^2$ = 0.9749) between the integrated counts over the whole detector and the degrader percentage, excluding the degrader 10 measurements. Frequency components in the intensity of the beam have been calculated for proton beams at 50 to 1000 FPS (frames per second), significant components at 252.51 Hz (σ = 0.83), 49.98 (σ = 0.29) and 30.55 (σ = 0.55) were observed.

Dose Delivery

• Antony Lomax (PSI)

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Superconducting gantry for proton therapy and imaging

• Ewa Oponowicz (University of Manchester/Cockcroft Institute)

Room: Salón de Actos *Introduction*: Proton computed tomography can reduce uncertainties in proton therapy treatment planning. It requires a 330 MeV proton beam for full imaging of an adult body and the beam rigidity increases to 2.8 Tm (from 2.3 Tm at 230 MeV). If such rotating beam delivery system is to be placed in a hospital-based facility, superconducting technology must be employed to minimise the gantry weight and volume. A compact superconducting gantry of large energy acceptance is presented. *Methods*: The initial gantry optics design was modelled in MAD-X, followed by the design of superconducting bending magnets. Canted cosine theta dipoles of 3.9 T central field were complete in Opera-3D software for electromagnetic simulations. Monte Carlo simulations of the full design, including the energy degrader mounted on the gantry, were performed in G4Beamline. *Results*: An isocentric superconducting gantry for both proton therapy and proton computed tomography was designed. It is an achromatic design with normal-conducting quadrupoles and superconducting CCT dipoles. The gantry is equipped with a boron carbide energy degrader to minimise space requirements and downstream pencil beam scanning system. *Discussion/Conclusions*: Whilst superconductivity ensures no significant volume reduction for typical proton treatment gantries, high field superconducting magnets are of benefit at higher energies. A compact large acceptance superconducting gantry can be placed in a conventional proton treatment room to deliver protons for both imaging and therapy. This improves the precision of treatment planning and allows for the patient’s setup to remain the same for both procedures.

Design considerations of a superconducting gantry with alternating-gradient combined-function magnets

• Bin Qin (Huazhong University of Science and Technology)

Room: Salón de Actos A proton therapy facility based on the superconducting cyclotron is under development in HUST (Huazhong University of Science and Technology), which uses warm magnets for beam transport lines and gantries. For future upgrade, a lightweight superconducting gantry is under consideration. This paper describes the design of a superconducting gantry with alternating-gradient combined-function magnets and downstream scanning. +/-15% momentum acceptance is achieved from demonstration of beam optics including high order aberrations and realistic fringe field effect. From the viewpoint of systematic design for this superconducting gantry, an integrated fast degrader and a compact scanner to perform fast 3D pencil beam scanning will also be introduced.

Public Talk - Acelerando partículas para tratar el cáncer

• María Isabel Gallardo

Monte Carlo Dosimetry

• Antonio Lallena (University of Granada)

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Review of the improved nuclear physics models in FLUKA for helium and carbon ion therapy

• Giulia Arico' (European Organization for Nuclear Research (CERN), Geneva, Switzerland)

Room: Salón de Actos FLUKA (Ferrari et al. 2005, Böhlen et al. 2014) is a multi-purpose Monte Carlo code for particle transport, developed by a CERN-INFN collaboration. In hadron therapy it is used to generate the basic input data for the treatment planning systems (e.g. at CNAO in Italy, and at HIT and MIT in Germany), to validate the dose calculations, and for research purposes (Battistoni et al. 2016). Besides proton and carbon ions, already in use in several facilities worlwide, HIT is planning to exploit helium ions for cancer treatments in the near future. In order to provide accurate dose calculations in FLUKA, as a support for the treatment planning system at HIT, refinements of the total and non-elastic cross section models embedded in FLUKA were carried out. Experimental data acquired at HIT (Horst et al. 2017, Horst et al. 2019) were used to benchmark the code. A better agreement between FLUKA and experimental measurements of depth-dose profiles was achieved, especially in the Bragg peak. The dose distributions predicted by the previous and revised FLUKA versions were compared in realistic clinical cases. This work is crucial in view of the use of helium ions for hadron therapy at HIT. For estimation of the cell lethal lesions induced by the radiotherapy treatments, accurate calculations of the RBE-weighted dose are needed. Different radiobiological models have been developed, among which there are the local effect model I (LEM I) (Scholz et al. 1997, Krämer and Scholz 2006) and the microdosimetric kinetic model (MKM) (Inaniwa et al. 2010), both used in clinics. LEM IV (Grün et al. 2012, Krämer et al. 2016) is a revised version of LEM I, which has been optimized particularly for heavy ions. In addition, the biophysical analysis of cell death and chromosome aberrations (BIANCA) model (Carante et al. 2018) has been developed at the University of Pavia and INFN-Pavia (Italy). In our research we interfaced the FLUKA code with the four above-mentioned radiobiological models. For a given physical dose, the resulting RBE-weighted dose distributions obtained using different models were compared. Real clinical cases treated at the CNAO facility were used for studies with primary carbon ions. Comparisons between simulations and in-vitro experimental data were performed for helium ion and carbon ion beams. The most relevant achievements will be presented. *References*: Battistoni G et al. 2016 The FLUKA Code: An Accurate Simulation Tool for Particle Therapy Front Oncol. 6: 116 Böhlen TT et al. 2014 The FLUKA Code: Developments and Challenges for High Energy and Medical Applications, Nuclear Data Sheets 120 211-14 Carante MP et al 2018 BIANCA, a physical model of a cell survival and chromosome damage by protons, C-ions and He-ions at energies and doses used in hadrontherapy, Phys. Med. Biol.63(7) 075007 Ferrari A et al. 2005 FLUKA: a multi-particle transport code, CERN-2005-10, INFN/TC-05/11, SLAC-R-773 Horst F et al. 2017 Measurement of charge- and mass-changing cross sections for 4He+12C collisions in the energy range 80–220 MeV/u for applications in ion beam therapy, Phys. Rev. C 96, 024624 Horst F et al. 2019 Measurement of 4He charge- and mass-changing cross sections on H, C, O, and Si targets in the energy range 70–220 MeV/u for radiation transport calculations in ion-beam therapy, Phys. Rev. C 99, 014603 Krämer M and Scholz M 2006 Rapid calculation of biological effects in ion radiotherapy, Phys. Med. Biol. 51 1959–70 Krämer M et al. 2016 Helium ions for radiotherapy? Physical and biological verifications of a novel treatment modality, Med. Phys. 43 1995 Grün R et al. 2012 Impact of enhancements in the local efffect model (LEM) on the predicted RBE-weighted target dose distribution in carbon ion therapy, Phys. Med. Biol. 57 7621-74 Inaniwa T et al. 2010 Treatment planning for a scanned carbon beam with a modified microdosimetric kinetic model Phys. Med. Biol. 55 6721 Scholz M et al. 1997 Computation of cell survival in heavy ion beams for therapy. The model and its approximation, Radiat Environ Biophys 36(1) 59-66

A data-driven nuclear fragmentation model for a fast Monte-Carlo code, FRED, in Particle Therapy with Carbon beams

• Micol De Simoni (Università di Roma "La Sapienza", Fisica, Rome, Italy)

Room: Salón de Actos To really exploit the potential benefits of Particle Therapy (PT), the highest possible accuracy in the calculation of dose and its spatial distribution is required in treatment planning. Commonly used Treatment Planning Software (TPS) solutions adopt a simplified beam–body interaction model using a 3D water equivalent representation of the patient morphology. An alternative is the use of Monte Carlo (MC) simulations which explicitly take into account the interaction of charged particles with actual human tissues. Full MC calculations are not routinely used in clinical practice because they typically demand for substantial computational resources and they are usually only used to check treatment plans for a restricted number of difficult cases. Therefore, presently one of the major issues related to TPS improvement is the high computational time required in order to meet the goal of high accuracy. The code FRED (Fast paRticle thErapy Dose evaluator) has been developed to allow a fast optimization of the treatment plans in charged PT while profiting from the dose release accuracy of a MC tool. Within FRED the proton and ion interactions are described with the precision level available in leading edge MC tools used for medical physics applications, with the advantage of reducing the simulation time up to a factor 1000. Moreover, running on GPU cards, the code allows a plan re-optimization in few minutes instead of several of hours on CPU hardware. FRED 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 and the code is already used as research tool for proton beams at several clinical and research centres in Europe (Krakow, Trento, Maastricht, Lyon). The excellent results achieved with protons determined the interest of the CNAO (Centro Nazionale di Adroterapia Oncologica) center (Pavia, Italy) to develop FRED also for Carbon therapy applications. Models for the interaction of Carbon ions with matter are currently under development to be implemented in the FRED code. In particular, the main difference is in the fragmentation of the projectile since protons do not fragment while ions do. As the beam fragmentation process is related to the dose release outside the tumor region its description is of paramount importance and has to be accurately modeled. Currently, the development of the model is based on the use of data taken during experiments at GANIL (laboratory of CAEN, France) where the fragmentation of Carbon ions on thin targets (H, C, O, Al and Ti) has been studied (J. Dudouet, et al, DOI:10.1103/PhysRevC.88.024606). To tune the algorithm in the energy range used in PT treatments, and not only at beam energies of the GANIL experiment, an appropriated scaling is used, obtaining energy and angular cross-sections specific for every energies. In the next future, new data from other experiments (i.e. FOOT experiment) will be used to improve the model. The status of new developments and the performance of FRED will be presented.

Monte Carlo modelling of the Clatterbridge Proton Therapy beamline for Beam Diagnostics integration

• Jacinta Yap (University of Liverpool / Cockcroft Institute)

Room: Salón de Actos The Clatterbridge Cancer Centre (CCC) in the United Kingdom is the world’s first hospital proton beam therapy facility, treating patients with ocular cancer since 1989. In recent years there has been rapid growth across Europe in both the demand and provision of particle radiation therapy treatments, with multiple centres under development in the UK. Correspondingly, this has brought about the need for advanced diagnostics and technologies, to fully exploit the fundamental benefits of ion beam therapy. One such device currently under development by the QUASAR group, is an online beam monitor based on LHCb VErtex LOcator (VELO) detector technology. The capability of the detector as a beam halo, dose monitor for clinical ion beam accelerators is being investigated and is planned for implementation into the CCC beamline. In order to assess the performance and suitability of the system, it is important to know the characteristics and operational parameters of the beam. Facility related constraints have required extensive study and modelling of the beamline and recent work toward complete characterisation of the beam is presented. This is the first comprehensive end-to-end model of the CCC beamline, developed using the Monte Carlo toolkit, Geant4 and with extensions, Beam Delivery Simulation (BDSIM) and TOol for PArticle Simulation (TOPAS). This has allowed the possibility of simulating the beam anywhere from the exit of the cyclotron to beyond the treatment nozzle and simulation results are shown alongside experimental measurements obtained for comparison and validation. The specific application of detector integration and several other anticipated outcomes is also discussed; planned experimental campaigns, halo maps for VELO and verification as a standard model for all related work performed at the beamline.

A Monte Carlo study of target fragmentation in Protontherapy

• Alessia Embriaco (INFN - National Institute for Nuclear Physics)

Room: Salón de Actos In protontherapy, secondary particles can be produced through primary beam interactions with the patient’s body. Fragments created in inelastic interactions of the beam with the target nuclei have low kinetic energy, high atomic number and high LET as compared to primary protons. These secondary particles produce an altered dose distribution, due to their different ranges. The residual range of such fragments is of the order of 10-100 $\mu m$ so they are in general confined within a single cell [1]. They have high LET, locally leading to an increase of RBE for the same delivered dose. The energy dependence of the nuclear interaction cross section makes target fragmentation relevant mostly in the entrance region [2] for normal healthy tissues. The inclusion of target fragmentation processes can be important for the accurate calculation of the dose in the treatment. Nowadays, target fragmentation is not implemented in commercial TPSs. Furthermore, the production yield of fragments at therapeutic energy is still poorly measured. In the MoVe IT (Modeling and Verification for Ion beam Treatment planning) project, the effect of target fragmentation will be included in the TPS. The TRiP98 code[3] is able to properly account for the mixed radiation field for the description of biological effects of target fragmentation. In order to implement the transport of fragments in the TPS, a database for fragments fluence will be created. In this work, Monte Carlo simulations were employed to evaluate the impact of target fragmentation in protontherapy. MC codes are able to take full account of the mixed radiation fields and provide detailed predictions of particles originating in the nuclear interactions [4]. To include the impact of fragmentation in the TPS and estimate the biological effect of fragments,the fluence of target fragments at different depths has been calculated with FLUKA MC code [5]. [1] F. Tommasino and M. Durante, Proton radiobiology. Cancers, 7(1):353–381, 2015. [2] T. Pfuhl et al., Dose build-up effects induced by delta electrons and target fragments in proton bragg curves - measurements and simulations. PMB, 63(17):175002, 2018 [3] M. Krämer and M Scholz, Treatment planning for heavy-ion radiotherapy: calculation and optimization of biologically effective dose. PMB, 45(11):3319–3330, 2000 [4] G. Battistoni et al., Nuclear physics and particle therapy. Advances in Physics, 1(4) (2016) 661-686 [5] A. Ferrari, P. R. Sala, A. Fasso, and J. Ranft, FLUKA: A multi-particle transport code(program version 2005). Technical report, 2005

Dosimetry and Quality Assurance

• Simon Marcelis (IBA)

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Luminescence imaging of proton beams in water: Is this method sufficient for use in clinical quality assurance?

• Jan Michael Burg (THM University of Applied Sciences, Giessen, Germany, University Medical Center Marburg Philipps-University, Marburg, Germany)

Room: Salón de Actos Proton therapy is increasingly used in modern radiation therapy. In the quality assurance of Proton therapy facilities, a recurring dosimetric task is the verification of the stability of the proton ranges in water for all energies provided by the system. The conventional measurement method using an ionization chamber with an adjustable water column (e.g. PTW Peakfinder) is very time-consuming, depending on the required spatial resolution and number of energies to be measured. The use of multi-layer ionization chambers (e.g. IBA Giraffe) is faster but limited in depth resolution. Recently, luminescence light emitted from water irradiated with proton beams has been depicted and was subject of different studies x1,2x. It turned out that this luminescence light is strong enough to be detected by sensitive cameras at the dose levels typical for proton therapy. The local intensity of the luminescence light appears to depend on the dose. In this work, we aim to prove the suitability of this method as a quality assurance tool in particle therapy, using the example of range measurements for proton beams within the therapeutical energy range. For this purpose, a comparative measurement between standard measurement using multi-layer ionization chambers and an optical measurement using a high sensitive CMOS Camera was carried out in an experiment at the Westdeutsches Protonentherapiezentrum Essen (WPE). This work shall examine if the optical system is usable in a proton treatment room or if it gets disturbed by scattered radiation. The possibility to measure the proton ranges in water over the entire clinical energy range shall be determined. Furthermore, it shall be observed if the spatial resolution is sufficient to measure the smallest possible range difference of the therapy system ![Figure 1: (left) recorded luminescence images for 100, 120, 150 MeV Protons. (right) scaled luminescence signal compared to measurement using multi-layer ionization chambers][1] ![Figure 2: Luminescence signals for an energy change of 0.5 MeV. The coloured curves represent the luminescence signals. For comparison, a measurement with a multi-layer ionization chamber is shown in black.][2] It has been proven that it is possible to measure the luminescence signal for a Bragg peak in pure water without any detector perturbation although the signal intensity is very weak. For the observation of the peak position, our measurements reach a high conformity with the peak position measured by a multi-layer ionization chamber. A statement about the relationship between dose and luminescence signal is challenging and will be subject of further investigations. (1) Radioluminescence in biomedicine: physics, applications, and models Y Helo et al 2014 Phys. Med. Biol.59 7107 (2)Luminescence imaging of water during proton-beam irradiation for range estimation. Seiichi Yamamoto, Toshiyuki Toshito, Satoshi Okumura, Masataka Komori Med Phys. 2015 Nov; 42(11): 6498–6506. doi: 10.1118/1.4932630 [1]: https://i.imgur.com/HI6MX5I.png [2]: https://i.imgur.com/StxlnSQ.png

Inter-fractional monitoring in Carbon ions Particle Therapy treatments with the Dose Profiler detector

• Marta Fischetti (INFN - National Institute for Nuclear Physics)

Room: Salón de Actos The use of C, He and O ions in Particle Therapy (PT) exploits the enhanced Relative Biological Effectiveness and Oxygen Enhancement Ratio of such projectiles to improve the treatment efficacy in damaging the cancerous cells while reducing the dose to the surrounding Organs At Risk. The possible occurrence of inter-fraction morphological changes into the patient or patient mis-positioning with respect to the planned position are taken into account by the Treatment Planning System introducing safety factors preventing the target volume under-dosage. The treatments are optimised also avoiding an over-dosage of the healthy tissues surrounding the tumour area at the cost of reducing the very high tumour control PT capability. An online monitoring device, whose technical implementation is still missing in clinical routine, is eagerly awaited in order fully profit from the PT efficacy reducing the needed safety margins. Nowadays in clinical practice the re-planning of the treatment, and hence the acquisition of a new Computed Tomography scan of the patient, is done only in the occurrence of macroscopic morphological changes or whenever severe toxicities are expected or observed. The Dose Profiler (DP) detector was developed within the INSIDE project as a beam range monitor for the CNAO (Centro Nazionale d’Adroterapia Oncologica) therapy center (Pavia, Italy) where it is currently installed and ready for use in the clinical environment. It consists of a scintillating fibre tracker that exploits the detection of charged secondary fragments escaping from the patient, reconstructing their emission vertex. The DP capability to spot the inter-fractional changes in the dose deposition has been investigated by means of a Monte Carlo simulation using the FLUKA software based on a dataset of patients that underwent a treatment re-planning because of the appearance of severe toxicites. The acquired emission profiles in different conditions have been compared by means of statistical tests. The expected performance of the technique for different treatments and patient conditions will be reviewed. The results have also been validated using the data taken during a clinical trial occurred at the therapy center of Pavia in the summer of 2019. The simulation and data-taking results will be discussed, in view of assessing the DP capability of spotting inter-fractional changes in clinical conditions.

Monitoring intra-fractional motion using a novel range telescope in a mixed He/C beam

• Laurent Kelleter (UCL)

Room: Salón de Actos It has been proposed recently that a mixed helium carbon beam could be used for online monitoring of carbon ion therapy. At the same energy per nucleon, helium ions have about three times the range of carbon ions, which would allow for certain tumours to simultaneously use the carbon beam for treatment and the helium beam for imaging (theranostics). Here, the results of a measurement in which simple PMMA phantoms as well as anthropomorphic phantoms have been irradiated with a helium and a carbon beam with the same parameters are presented. The helium peak and the carbon tail exiting the phantoms are detected using a novel range telescope made of thin plastic scintillator sheets read out by a flat panel CMOS sensor. It is shown that a 10:1 carbon to helium mixing ratio generates a helium signal well above the carbon background while only adding 0.5% to the RBE-corrected dose in the carbon SOBP. A small air gap of 1 mm thickness in the simple PMMA phantom can be detected, demonstrating the achievable sensitivity of the presented method. In anthropomorphic phantoms it is shown that small displacements and rotations of the phantom as well as simulated rectal gassing cause detectable changes in the He/C beam exiting the phantom. The future prospects and limitations of the helium-carbon mixing as well as its technical feasibility are discussed. The group is currently working towards a system for real-time theranostics for carbon therapy.

Treatment facility optimization

• Andrea De Franco (EBG MedAustron)

Room: Salón de Actos MedAustron is an Ion Beam Therapy center where patients are treated with protons and carbon ions beams. A performance increase project has been started in 2016 in parallel to further commissioning of the facility. The machine was and keep being optimized to reduce the time necessary for a treatment, in order to increase patient throughput, enhance safety and quality of the treatment and provide a more comfortable therapy experience to patients. The improvements range from upgrades of the control system to optimization of the beam dynamics of the third order slow extraction. In this work we present the machine limitations, a cost/benefit analysis of different solutions, the achieved improvements and a look into the future.

Preparation of a radiobiology beam-line at the 18 MeV proton cyclotron facility at CNA

• Anna Baratto-Roldán (Centro Nacional de Aceleradores / Universidad de Sevilla)

Room: Salón de Actos Biophysical investigations using particle accelerators have gained interest in the last decades, coinciding with the spread of particle therapy centres worldwide and with the establishment of proton and ion therapy as recognized treatments for different types of tumours, with excellent clinical outcomes. Radiobiological experiments at proton and heavy-ion accelerators pose stringent conditions both on the physical and on the biological point of view. Firstly, a homogeneous dose distribution throughout the biological sample must be ensured, with a meaningful dose rate comparable to that used in the clinic (of the order of 2 Gy/min). Furthermore, when dealing with low-energy accelerators, the limited particle range makes it difficult to irradiate samples in tissue flasks filled with medium, meaning that cells must be exposed inside open culture vessels, vulnerable to bacterial contaminations. Finally, as biological targets are always made of living material, the environmental parameters such as room temperature, air pressure and humidity must be taken under control, to ensure that there is no additional impact on the cell viability. At the National Centre of Accelerators (CNA) in Seville, Spain, the experimental beam line installed at the 18 MeV proton cyclotron facility has been adapted for the irradiation of mono-layer cell cultures placed vertically with respect to the beam. In order to improve the homogeneity and decrease the beam intensity, a completely defocused beam has been used, scattering it 1.7 m upstream the exit window by placing an aluminium foil of 0.5 mm thickness. With these arrangements, a beam of 14.5 MeV is extracted, with a size of 4 mm diameter. Measurements have been done at different distances from the beam exit window to find the best conditions for the irradiation of biological samples, ensuring homogeneous dose profiles with deviations lower than 5% in the central 35 mm of the beam. Furhtermore, dosimetric studies using EBT3 radiochromic films and a transmission ionization chamber have been performed and compared with a Geant4 Monte Carlo simulation, which reproduces accurately the cyclotron beam properties and experimental setup. Finally, a preliminary experiment with cell cultures has been carried out irradiating human bone osteosarcoma epithelial cells with two different proton doses.

Light ion therapy software for data exchange

• Carlos Afonso (Centro Nazionale di Adroterapia Oncologica)

Room: Salón de Actos The Italian National Center for Oncological Hadrontherapy is currently upgrading one of the software environments of its medical accelerator control system. This environment, named configuration and support environment, is tasked with the configuration of accelerator components, management of the control system repository, and other support tasks. The objective of the three year technological upgrade project is to integrate of mobile devices into the environment, and update the technological stack used, resulting in a more maintainable, testable, and versatile software layer. For this project, product line architecture was designed for the new applications in this environment, which will slowly replace the legacy applications, while coexisting with them. A service oriented development approach was chosen, resulting in the development of several REST API services. Additionally, commonly used operations were implemented as reusable libraries, and a skeleton application generator, designed to create customized, yet fully functional, base applications. This talk aims to describe the lifecycle of this project, while presenting several challenges tackled in areas such as authentication and authorization, planning for efficient medical certification, separation of concerns, and platform interoperability.​

Advancements in particle therapy systems - acceleration and delivery

• Jonathan Farr (ADAM S.A.)

Room: Salón de Actos Although the use of particle therapy continues to expand, specific challenges inhibit its broader penetration as well as its clinical efficacy under certain conditions: The size and cost of particle therapy systems and their operation are restrictions. Also, technical limitations associated with the achievable level of dose conformality often hinder the advancement of particle therapy in comparison to conventional techniques. Current and up and coming technical innovations that may overcome these challenges will be discussed, including novel advancements in beam production, as well as advanced particle therapy delivery techniques.

4D Patient monitoring

• Guido Baroni (CNAO)

Room: Salón de Actos

Organ motion quantification and margins evaluation in carbon ion therapy of abdominal lesions

• Charalampos Kalantzopoulos (Centro Nazionale di Adroterapia Oncologica)

Room: Salón de Actos In particle therapy, image guidance is vital for planning and treating, especially for abdominal lesions, where the respiratory motion hinders treatment accuracy. In this study, fast acquired interleaved 2D CINE MR images were used to quantify the tumour (GTV) motion over several breathing cycles, to evaluate the clinical approach based on deriving an internal target volume (ITV) from a 4DCT. Data from seven patients treated with pencil-beam scanning carbon-ion therapy for abdominal lesions at the National Centre of Oncological Hadron-therapy (CNAO, Italy) were considered. For moving targets, a combined approach with abdominal compression, rescanning and gating at end-exhale is employed. The MR scan was performed on the same day of 4DCT acquisition. For 4 patients, an additional MR was acquired approximately after 1 week. The 2D CINE MR (300 frames acquired in 1.13 min) images centered on the target, along with a deformable image registration algorithm were used to quantify tumour motion. Afterwards, two ITVs were defined considering: (1) all the respiratory phases ($ITV_FB$), (2) only phases within the gating window ($ITV_G$). The generated ITVs were compared with the clinical ITV ($ITV_C$) as defined at CNAO using phases within 30%-exhale and 30%-inhale of the 4DCT. CINE MRI captured images from 12-20 breathing cycles in contrast to 4 from 4DCT. The ITV normalized for the GTV had median(iqr) values of 0.15(0.19), 0.32(0.52) and 0.8(0.97) for $ITV_C$, $ITV_G$ and $ITV_FB$, respectively. The median(iqr) Hausdorff distances (p=95%) from the GTV were 3.40(1.57), 2.18(2.23) and 9.71(6.99) mm for $ITV_C$, $ITV_G$ and $ITV_FB$, respectively. According to both metrics, the $ITV_C$ was significantly different from the $ITV_FB$, but not significantly different form $ITV_G$. Spatial differences between $ITV_G$ and $ITV_C$ are due to more breathing cycles captured by MR, thought these were not-significantly different, indicating the effectiveness of the adopted gating approach to mitigate tumour motion.

Optimization of high-performance 3D/4D surface scanning technology for patient monitoring in radiotherapy environment

• Roland Höfling (ViALUX GmbH)

Room: Salón de Actos Nowadays different electronic devices are used in radiotherapy to improve and optimize the treat-ments. The scattered radiation in the radiotherapy environment can cause failures and/or damages to the electronics and therefore the devices must be radiation resistant in order to assure a secure treatment. ViALUX developed in the last years a new 3D scanning technology that allows increasing the performance of its previous 3D scanners, in particular in terms of speed, precision and interface. Since these new devices will be used also in radiotherapy for patient positioning and monitoring, a radiation hardness test is necessary to assess their reliability in this environment. The devices were tested during short tests in the conventional radiotherapy and carbon therapy environment and during a 2-day radiation test at FRM II nuclear reactor. Temporary malfunctions due to Single Event Effects and permanent damages due to the Total Ionizing Dose were investigated. The ViALUX 3D scanners showed a good reliability in the radiotherapy environment, except from rare and recoverable interruptions of functionality detected during the tests at the nuclear reactor. The CMOS image sensor, which is a key part of the 3D scanners, showed an increase in the number of bright pixels after the irradiation. Further analysis showed that these bright pixels don’t affect the 3D image quality in the typical working conditions (no gain, exposure time < 10 ms). Hardware and software solutions to further improve the 3D scanners radiation hardness are currently under study.

A Modular Control System for Treating Moving Targets with Scanned Ion Beams: Design, Development, and Preliminary Test Results

• Michelle Lis (GSI Helmholtzzentrum fur Schwerionenforschung, Louisiana State University)

Room: Salón de Actos **Introduction** Lung and other thoracic cancer survival rates have shown limited improvements despite generally more effective local control rates. Scanned particle beam therapy has the potential for dose escalation while sparing healthy tissue, but it requires a practicable solution to the longstanding problem of the adverse effects from the interplay of moving ion beams and moving tumors. We designed and implemented a modular dose delivery system to synchronize moving tumors with scanned ion beams for safer and more effective treatment of late stage lung cancers and lung metastases. This capability will enable subsequent clinical studies to evaluate the role of scanned ion beams in treating moving tumors. The objective of this study is to confirm that a modular dose delivery system which synchronizes the motion of tumors and scanned ion beams can irradiate tumors with portability, safety, and dosimetric accuracy, while sparing surrounding healthy tissues. **Methods and Materials** A modular motion-synchronized dose delivery system (M-DDS) was designed, developed and tested at GSI Helmholtz Centre for Heavy Ion Research and Centro Nazionale di Adroterapia Oncologica (CNAO). The operation of the M-DDS and its subsystems, including the timing, beam request, detector, magnet, memory, and motion mitigation systems, was validated to ensure the M-DDS, when integrated into the treatment control system, functions according to design specifications. This as done by testing the transmission, reception, timing, and synchronization of signals used by each subsystem. Integration tests were performed by delivering test-case library of 10 3-dimensional (static) treatment plans, which together comprise a complete plan for a moving tumor. Additionally, the interlock and safety systems within the M-DDS were tested by inducing a series of critical and non-critical errors. Finally, the quality of delivered dose distributions was assessed in simple geometries by considering dosimetric uniformity and conformity. Simple geometries were delivered to a 2-dimensional ionization chamber array detector and radiochromic films mounted on a sinusoidal moving platform. Various plans designed for 1, 3, 6, and 10 respiratory states were delivered to investigate the degree of motion compensation and the extent of residual motion within a single motion state. The delivered geometries were assessed for delivery quality via gamma index analysis with a 3%/3mm criteria. **Results** The modular M-DDS subsystem functionality, motion mitigation functionalities, and treatment delivery were experimentally verified, including synchronization of timing events, magnet interfaces, beam request software and beam monitors. Loading of treatment plan libraries into dynamic random access memory (DRAM) and synchronous delivery, where treatment sequence is directed by the detected motion state was verified. Duty cycles of 80-95% were achieved for these deliveries. The performance of a critical component of DDS safety, the gating system, was also verified at both GSI and CNAO. Complete beam disruption was possible with the chopper magnet, while residual intensities on the order of 10 % of full intensity compromised experimental results at GSI. At both facilities, rapid gating was verified. The delivered geometries were assessed for delivery quality via gamma index analysis with a 3%/3mm criteria. 6 and 10 motion phase plans for 40 and 20 mm amplitude motion showed >95% gamma index pass rates for 50x50mm squares at CNAO. A homogeneity of 90% was measured for 50x100mm rectangles at GSI. Dose outside the target region showed a rapid fall-off, comparable to static plans. **Summary** Preliminary results have validated the basic functionality and feasibility of the implemented motion mitigation strategy. Further tests, including clinical safety and more complex phantoms are necessary to translate this strategy to lung or pancreas cancer patients.

Uncertainty Quantification Analysis and Optimization For Proton Therapy Beam Lines

• Valeria Rizzoglio (Paul Scherrer Institut)

Room: Salón de Actos Since many years, proton therapy is used as an effective treatment solution against deep-seated tumors. A precise quantification of sources of uncertainties in each proton therapy aspect (e.g. accelerator, beam lines, patient positioning, treatment planning) is of extreme importance to increase the robustness of the dose delivered to the patient. Together with Monte Carlo techniques, a new research field called Uncertainty Quantification (UQ) has been recently introduced to verify the robustness of the treatment planning. We apply here, for the first time, UQ methods to identify the typical errors in transport lines of a cyclotron-based proton therapy facility and analyze their impact on the properties of the therapeutic beams. The potential of UQ methods in developing optimized beam optics solutions for high-dimensional problems is also demonstrated. Sensitivity analysis and surrogate models offer a fast way to exclude unimportant parameters from complex optimization problems such as the superconducting gantry project studied at Paul Scherrer Institut in Switzerland.

The upcoming European Joint Research Project “Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates”

• Andreas Schüller (Physikalisch-Technische Bundesanstalt (PTB))

Room: Salón de Actos Several animal studies demonstrated that delivering radiation dose in a short time, i.e. with only a few beam pulses of ultra-high dose per pulse, may dramatically reduce adverse side effects, while the anti-tumoural efficacy is preserved. Due to this so-called FLASH effect, the prescribed dose could also be increased resulting in a more effective tumour control. The future application of FLASH radiation therapy requires that its performance, safety and effectiveness are reliably measured and optimised. Accurate dosimetry is vital in delivering successful radiotherapy. Additionally, laser-driven accelerators are being considered as the next generation of cost-effective accelerators for radiotherapy, which enable further alternative advanced treatment modalities. Furthermore, novel laser wakefield accelerators allow the cost-effective generation of very high energy electrons (VHEE) which enable further alternative advanced treatment modalities, as for e.g. VHEE radiotherapy. The pulse duration of laser-driven beams is much shorter than that of conventional clinical accelerators and the dose rate in the pulse can be orders of magnitude higher. FLASH radiotherapy, VHEE radiotherapy as well as laser-driven beams, cause significant metrological challenges related to the ultra-high pulse dose rates, which need to be addressed to enable the translation of these advanced radiotherapy techniques to clinical practice. The complexity and the resources needed for research in advanced radiation therapy using particle beams with ultra-high pulse dose rates requires wide, multidisciplinary scientific approaches that go beyond the capabilities of a single research institute. In the framework of the European Metrology Programme for Innovation and Research (EMPIR) the Joint Research Project “Metrology for advanced radiotherapy using particle beams with ultra-high pulse dose rates” will address this problem. This work outlines the challenges and approaches at dosimetry for particle beams with ultra-high pulse dose rates and introduces the partners of the EMPIR research consortium as well as their task allocation.

Challenges in assessing risks for particle accelerators as medical devices

• Roberto Filippini (EBG MedAustron GmbH)

Room: Salón de Actos Particle accelerators used for cancer treatment have made tremendous progress in the recent decades in respect to performance, dose delivery and control techniques as well as their usability within clinical environments. This area is currently experiencing a growing development that promises even bigger achievements in the future regarding treatable indications, cure rates and side effects. More effective medical prescriptions will be technically feasible, with a resulting higher chance of healing and quality of life for the patient. The required higher beam intensities and precision of dose distribution for the treatment of patients increase the consequences and risks for the patients in case of failure of the particle accelerator, caused by either technical faults or human errors. This means that every progress in this field needs to be accompanied by an effective risk management process leading to an acceptable level of residual risk in relation to the expected clinical benefit. The European Medical Device Directive (93/42/EEC) and the European Medical Device Regulation (2017/745/EU) define requirements for dealing with safety and performance for medical devices, including the implementation of risk management processes and application of medical safety standards. Compliance with these requirements turns to be particularly challenging for a particle therapy accelerator. This contribution summarizes the risk management experience gained for the MedAustron Particle Therapy Accelerator with a focus on the results from the risk assessment and a few examples.

Digital LLRF system: concepts and requirements for proton therapy based on a linear accelerator

• Borut Baricevic (Instrumentation Technologies)

Room: Salón de Actos Modern particle therapy requires systems which enable precise control over delivered dose depth. That translates into the ability to program the accelerator to quickly modulate the beam energy in order to deposit the treatment dose into predefined tissue regions. In particle therapy applications linear accelerators have advantages in terms of compactness and beam modulation ability. However to control the particle acceleration process from the beginning it’s crucial to precisely stabilize the RF field inside the cavities through Low Level Radio Frequency feedback system. This talk introduces the concepts and the specific requirements of a LLRF system for a proton therapy LINAC. As an example the Libera LLRF implementation for the AVO-ADAM LIGHT linear accelerator will be presented.

Summary

• Carsten Peter Welsch (Cockcroft Institute / University of Liverpool)

Room: Salón de Actos