The use of C, He and O ions as projectiles in Particle Therapy (PT) treatments is getting more and more widespread as a consequence of their enhanced relative biological eﬀectiveness and oxygen enhancement ratio, when compared to the protons one. The advantages related to the incoming radiation improved eﬃcacy are requiring an accurate online monitor of the dose release spatial distribution. Such monitor is necessary to prevent unwanted damage to the tissues surrounding the tumour that can arise, for example, due to morphological changes occurred in the patient during the treatment with respect to the initial CT scan. PT treatments with ions can be monitored by detecting the secondary radiation produced by the primary beam interactions with the patient body along the path towards the target volume. Charged fragments produced in the nuclear process of projectile fragmentation can be emitted at large angles with respect to the incoming beam direction and can be detected with high eﬃciency in a nearly background-free environment. The Dose Proﬁler (DP) detector, developed within the INSIDE project, is a scintillating ﬁbre tracker that allows an online reconstruction and backtracking of such secondary charged fragments. The construction and preliminary in-room tests performed on the DP, carried out using the 12C ions beam of the CNAO treatment centre using an anthropomorphic phantom as a target, will be reviewed in this contribution. The impact of the secondary fragments interactions with the patient body will be discussed in view of a clinical application. Furthermore, the results implications for a pre-clinical trial on CNAO patients, foreseen in 2019, will be discussed

Battistoni, G.

De Simoni, M.

Dong, Y.

Embriaco, A.

Fischetti, M.

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DOI 10.1393/ncc/i2018-18209-2Colloquia: SIRR 2018IL NUOVO CIMENTO 41 C (2018) 209In-room test results at CNAO of an innovative PT treatmentsonline monitor (Dose Profiler)M. De Simoni(4)(5), G. Battistoni(7), Y. Dong(6)(7), A. Embriaco(7),M. Fischetti(1)(5), C. Mancini Terracciano(4)(5), M. Marafini(2)(5),R. Mirabelli(4)(5)(2), S. Muraro(8), V. Patera(1)(2)(5), A. Sarti(1)(2)(3),A. Schiavi(1)(5), A. Sciubba(1)(2)(5), E. Solfaroli Camillocci(4)(5)(9),G. Traini(4)(5)(2)(∗), S. M. Valle(6)(7) and I. Mattei(7)(1) Università di Roma “La Sapienza”, Dipartimento di Scienze di Base e Applicate perl’Ingegneria - Rome, Italy(2) Museo Storico della Fisica e Centro Studi e Ricerche “E. Fermi” - Rome, Italy(3) Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Frascati - Frascati, Italy(4) Università di Roma “La Sapienza”, Dipartimento di Fisica - Rome, Italy(5) Istituto Nazionale di Fisica Nucleare, Sezione di Roma - Rome, Italy(6) Università di Milano, Dipartimento di Fisica - Milan, Italy(7) Istituto Nazionale di Fisica Nucleare, Sezione di Milano - Milan, Italy(8) Istituto Nazionale di Fisica Nucleare, Sezione di Pisa - Pisa, Italy(9) Università di Roma “La Sapienza”, Scuola di specializzazione in Fisica Medica - Rome,Italyreceived 4 December 2018Summary. — The use of C, He and O ions as projectiles in Particle Therapy (PT)treatments is getting more and more widespread as a consequence of their enhancedrelative biological effectiveness and oxygen enhancement ratio, when compared tothe protons one. The advantages related to the incoming radiation improved efficacyare requiring an accurate online monitor of the dose release spatial distribution.Such monitor is necessary to prevent unwanted damage to the tissues surroundingthe tumour that can arise, for example, due to morphological changes occurred in thepatient during the treatment with respect to the initial CT scan. PT treatments withions can be monitored by detecting the secondary radiation produced by the primarybeam interactions with the patient body along the path towards the target volume.Charged fragments produced in the nuclear process of projectile fragmentation canbe emitted at large angles with respect to the incoming beam direction and can bedetected with high efficiency in a nearly background-free environment. The DoseProfiler (DP) detector, developed within the INSIDE project, is a scintillating fibretracker that allows an online reconstruction and backtracking of such secondarycharged fragments. The construction and preliminary in-room tests performed onthe DP, carried out using the 12C ions beam of the CNAO treatment centre usingan anthropomorphic phantom as a target, will be reviewed in this contribution.The impact of the secondary fragments interactions with the patient body will bediscussed in view of a clinical application. Furthermore, the results implications fora pre-clinical trial on CNAO patients, foreseen in 2019, will be discussed.(∗) Corresponding author. E-mail: giacomo.traini@roma1.infn.itCreative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by/4.0) 12 M. DE SIMONI et al.1. – IntroductionProton and carbon ion beams are currently used to treat deep-seated solid tumorsresistant to the conventional radiotherapy, in particular when located close to OrgansAt Risk (OAR) [1]. When compared to standard radiotherapy treatments, the mainadvantage of this technique is the improved localization of the irradiated dose in thetumor region that helps in sparing the surrounding healthy tissues and organs. Chargedparticles lose most of their energy at the end of their path, in the region called “BraggPeak (BP)”, while the dose deposited by X-rays is exponentially decreasing as a functionof the photons range inside the matter (fig. 1). Currently, the proton treatments are themost common, but the use of carbon beams has known an increase, at least in Europein the last 10 years, with the beginning of the operation of several new facilities.The intrinsic precision, due to the peculiar features of dose release in the BP region,is jeopardized by uncertainties in the knowledge of the actual primary particle range.Inhomogeneities, computed tomography artifacts, conversion to electronic density, in-tersession anatomical/physiological changes can lead to sensible range variations with asensible change in the dose released in the target volume. New online dose monitoringdevices have to be introduced into clinical use to avoid the risk to hit healthy organs andto take full advantage of the ability of particle therapy to deliver the dose to the PlannedTreatment Volume (PTV) [2,3]. Currently, no technical solution is availble for the onlinemonitoring of PT treatments that are involving “heavy ions” (Z > 1). Attempts touse PET scans immediately after the treatment, to validate the treatment quality, arereported in the literature (for a review see [4]).Primary beam particles cannot be used for dose range monitoring, as they do notescape from the patient. A promising approach consists in the detection of the secondaryparticles (PET photons, prompt photons, neutrons and charged particles) produced bythe nuclear interactions between the primary beam with the crossed tissues.It has already been shown that the Bragg peak can be correlated with the emissionpattern of secondary prompt photons in the energy range 1–10 MeV [5,6] and secondaryFig. 1. – Physical dose release along the path traveled in matter for X-rays (green) and an ionbeam (red). The tumor position is represented in light blue.IN-ROOM TEST RESULTS AT CNAO ETC. 3-10 0 10Arbitrary Units / 0.4 cm01020304050607080z [cm]Charged EmissionReleased DoseFig. 2. – Longitudinal emission profile of charged secondary particles, detected at 90◦ withrespect to the beam direction, produced by a 220MeV/u 12C ion beam impinging on a PMMAtarget. The depth-dose distribution (hatched area) is superimposed [8].charged particles with kinetic energies up to a few hundred MeV [7] (fig. 2). The car-bon beam produces higher-energy, secondary charged particles with a larger flux whencompared to the proton beam case. The detection of the neutral hadronic component(neutrons) is experimentally more demanding, but would allow to reach a significantstatistics of detected particles, as they are abundantly produced even in proton treat-ments.2. – Dose Profiler and INSIDE projectThe Dose Profiler (DP) detector has been designed to detect the secondary chargedparticles (mostly protons) emitted as products of the nuclear fragmentation of the pro-jectile (beam of 12C). Those particles can be detected with a high efficiency and a smallbackground achieving a high backtracking resolution. The largest fraction of the frag-ments is forward peaked, and it is mostly contained within a cone of few degrees withrespect to the beam axis. However, the proton component shows a significant tail at largeemission angles. These results have triggered several studies on the possibility to exploitcharged fragments for monitoring purposes. In fact, large angles production is the mostinteresting for monitoring applications, because of the advantageous proton reconstruc-tion resolution (the uncertainty on the emission point reconstruction is proportional to(sin θ)−1, where θ is the proton emission angle), and for the difficulties related to thepositioning in the treatment room of a detector along the incoming beam direction. Itis expected that the charged particles yield at large angles remains relevant in the caseof beams of particles heavier than protons [8]. Therefore, the potential use of chargedparticles detection for the PT treatments online monitoring can be especially appealingin 12C therapy.The DP has been developed in the framework of the INSIDE (Innovative Solution formonitoring in Hadrontherapy) project in order to work in a dual in-beam dose monitoringsystem able to detect at the same time secondary protons with the DP and, with a PET-γdetector, back-to-back photons from the annihilation of positrons emitted by β+-decayingisotopes produced in the patient by the therapeutic proton or carbon ion beams. Thewhole system, shown in fig. 3, is planned to be integrated in the treatment room of4 M. DE SIMONI et al.Fig. 3. – INSIDE: pictorial representation of the integration of the INSIDE simultaneous in-beam dose monitoring system developed for the online control of proton and carbon ions beamsin the treatment room of CNAO.CNAO (Centro Nazionale di Adroterapia Oncologia), in Pavia (Italy).The DP design has been optimized targeting the measurement of the charged sec-ondary particles tracks in the energy range 50–150 MeV. The aim is to assess the beamrange from the reconstructed spatial emission shape, built extrapolating the detectedtracks towards the beam direction. The detector is also capable of measuring the chargedfragments kinetic energy, in order to refine, if needed, the data sample excluding the slow-est fragments, that suffer from larger multiple scattering.The tracking system is based on eight couples of orthogonal layers (19.2 × 19.2 cm2)composed by plastic scintillating fibres (500 × 500μm2) as represented in fig. 4.When a charged particle travels through a layer, it deposits energy in the scintillatingfibres creating scintillation photons. A small fraction of the scintillation light is thenguided by total internal reflection to the fibre ends, where it is detected by a SiliconPhotoMultiplier (SiPM) detector. The inter-plane distance is 2 cm, which correspondsto the minimum gap allowed by the front-end electronics, in order to maximise thedetector angular acceptance and the compactness as well.Fig. 4. – Left: schematic representation of the Dose Profiler. Right: view of the Dose Profilerlayers during the assembly phase.IN-ROOM TEST RESULTS AT CNAO ETC. 5The DP was assembled in May 2017 in the mechanical workshop of the Scienze di BaseApplicate per l’Ingegneria (SBAI) department (University of Rome, “La Sapienza”).3. – Benchmarking the detector performances using proton and carbon ionsbeamsIn May 2017, the detector has undergone a performance characterization using theexperimental room of the Trento proton therapy centre using protons beams at theenergies of interest of PT. In July and November 2017 it was finally tested at CNAO tocheck the operation in “clinical-like conditions”.In the Trento facility, the DP has been tested using proton beams of ∼103 p/s intensitywith known monochromatic energy. The detector entrance face was 50 cm far awayfrom the room isocentre to simulate a clinical condition. The distribution of the chargedeposited in the fibers has been studied. The total amount of released charge Qfib in thefibers is shown in fig. 5. The charge resolution has been evaluated using a normalizedvalue:(1) QNfib =QfibNlay,where Nlay is the number of layers which have at least one cluster above threshold.To evaluate the Dose Profiler efficiency, the detector has been irradiated with protonbeams at 228 MeV, 159 MeV, 112 MeV, 70 MeV and 44 MeV, impinging the device centerand with protons at 91 MeV, continuously moving the Dose Profiler position (using aremotely movable platform) with respect to the beam direction in order to test the fulldetector active volume. The layer detection efficiency εiν has been evaluated for eachfibre layer i separately for the two views ν = x, y (each one corresponding to one of thelayers of the orthogonal couple). The layer efficiencies resulting by the full volume scanat 91 MeV (∼3 × 106 events) are reported in fig. 6. For the first 6 layers in each viewthe detection efficiency is of the order of 90%, which is an expected value consideringFig. 5. – Distributions of the normalized deposited charge in the fibres for different energies.The normalization is done using eq. (1).6 M. DE SIMONI et al.Fig. 6. – Detection efficiency for the first six fibre planes in each view: the layers oriented in thex-view and the y-view are shown in the left and right panels, respectively.Fig. 7. – Left: setup of the test with a small plastic spherical target to simulate a point sourceof secondary fragments. The diameter of the sphere is 4 mm. Right: per-track resolution perdistance from target. The operational distance at CNAO is ∼50 cm.the dead space between the fibers, the fibre cladding and the possible light collectioninefficiencies in the coupling with read-out electronics.A per-track resolution (fig. 7) has been evaluated using a small plastic spherical target(diameter of 4 mm). The resolution at 50 cm (∼0.75 cm) was measured in the very sameoperational condition at CNAO and so it is the one that will be taken into account inthe analysis.During the test beam at CNAO, the interactions of pencil beams of different energieswere studied using different targets and the RANDO R© anthropomorphic phantom (fig. 8,left). After the calibration done in Trento, it was possible to correlate the charge de-posited in the fibres with the energy of the secondary fragments. Using beams of 12C withenergy of 180, 220, 280 MeV/u, the distributions of energy represented in fig. 8 (right)was obtained. The detected fragments have average kinetic energies of ∼100–120 MeV.The cut at ∼50 MeV is caused by the trigger threshold.The tests showed that the rate incurred by the DP reaches up to a value of 150 kHz.It is possible to detect charged particles at a high rate thanks to the fact that the deadtime of the detector is ∼5 μs. In clinical applications, where one must be able to exploitall the available statistics delivered in small quantity and in a very rapid time, going tohigh rates is crucial.IN-ROOM TEST RESULTS AT CNAO ETC. 7Fig. 8. – Left: setup of the CNAO test beam using RANDOR© as target. Right: the distributionof the detected charged particles’ energy for three different energies of the primary 12C beams:180MeV/u (blue), 220 MeV/u (black) and 280 MeV/u (red).4. – Accounting for secondary-particles interactions with matterCharged particles suffer from absorption and multiple scattering interactions in matterwhich must be considered during the reconstruction.The final precision achievable on the Bragg peak position depends on how muchstatistics can be collected and how well the interaction of the ions beams and of theemitted fragments with the patient body is handled.A first approach of this matter effect has been to use a full MC to realize a weightthat could consider the amount of absorbed particles (fig. 9). The simulation was basedon the study of the interactions between fragments and a water target. This allows anexperimental calibration.Another approach under development is the “PET-like” Maximum Likelihood Expec-tation Maximization (MLEM) one. The idea is to use a fast GPU (Graphics ProcessingUnit)-based MC software to compute a correlation matrix, for each Pencil Beam, thatFig. 9. – MC simulation of the production of secondary charged fragments in RANDOR© usinga 12C beam of 300MeV/u. The backtracking distribution of the detected particles is shownin red. The real distribution of production is represented in black and the unfolding using theweight is reported in green.8 M. DE SIMONI et al.can be applied to realize an unfolding from the detected distribution to the productionone. The advantage of using this method is that, thanks to the use of GPU, it can beused online.5. – ConclusionThe Dose Profiler tracer has been extensively tested with protons and fragmentswith characteristics similar to those expected in a clinical treatment, confirming thatthe detector expectations of resolution and efficiency are met. A clinical trial at CNAOusing the DP and PET detector is scheduled to start in 2019. Four pathologies wereselected: Meningioma and Nasopharynx Cancer that are usually treated with protonbeams; Adenoid Cystic Carcinoma (ACC) and Clival Chordoma treated with carbon ionbeams. The first two pathologies, treated using protons, are going to be monitored withthe PET detector, the others can be used with both devices. Those pathologies havebeen chosen as they represent two different operational situations: the ACC is usuallysubjected to a large morphological change, while in the Clival Chordoma the volumetreated is expected to conserve its density. The data obtained during the treatment willbe analyzed offline, completing the studies on the matter effects, and in this way it willbe possible to finalize the accuracy on the monitoring of the BP achievable in clinicalconditions.∗ ∗ ∗The authors thank TIFPA, the Trento protontherapy center and the CNAO staff forbeam-time and support during the data taking. We also acknowledge CNAO for financialsupport in the DP activity. We also thank Marco Magi (SBAI) and the electronic serviceat LNF for the Dose Profiler design and realization.REFERENCES[1] Amaldi U. and Kraft G., Rep. Prog. Phys., 68 (2005) 1861.[2] Faccini R. and Patera V., Mod. Phys. Lett. A, 30 (2015) 1540023.[3] Kraan A. C., Front. Oncol., 5 (2015) 150.[4] Parodi K., Med. Phys., 42 (2015) 7153.[5] Testa M., Bajard M., Chevallier M., Dauvergne D., Freud N., Henriquet P.et al., Radiat. Environ. Biophys., 49 (2010) 337.[6] Agodi C., Bellini F., Cirrone G. A. P., Collamati F., Cuttone G., De Lucia E.et al., J. Instrum., 7 (2012) P03001.[7] Piersanti L., Bellini F., Bini F., Collamati F., De Lucia E., Durante M. et al.,Phys. Med. Biol., 59 (2014) 1857.[8] Piersanti L. et al., Phys. Med. Biol., 59 (2014) 1857.

In-room test results at CNAO of an innovative PT treatments online monitor (Dose Proﬁler)

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In-room test results at CNAO of an innovative PT treatments online monitor (Dose Proﬁler)

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