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Purpose: Highly conformal scanned Carbon Ion Radiotherapy (CIRT) might permit dose escalation and improved local control in advanced stage thoracic tumors, but is challenged by target motion. Dose calculation algorithms typically assume a periodically repeating, regular motion. To assess the effect of realistic, irregular motion, new algorithms of validated accuracy are needed. Methods: We extended an in-house treatment planning system to calculate RBE-weighted dose distributions in CIRT on non-periodic CT image sequences. Dosimetric accuracy was validated experimentally on a moving, time-resolved ionization chamber array. Log-file based dose reconstructions were compared by gamma analysis and correlation to measurements at every intermediate detector frame during delivery. The impact of irregular motion on treatment quality was simulated on a virtual 4DCT thorax phantom. Periodic motion was compared to motion with varying amplitude and period ± baseline drift. Rescanning as a mitigation strategy was assessed on all scenarios. Results: In experimental validation, average gamma pass rates were 99.89+-0.30% for 3%/3 mm and 88.2+-2.2% for 2%/2 mm criteria. Average correlation for integral dose distributions was 0.990 ± 0.002. Median correlation for single 200 ms frames was 0.947 ± 0.006. In the simulations, irregular motion deteriorated V95 target coverage to 81.2%, 76.6% and 79.0% for regular, irregular motion and irregular motion with base-line drift, respectively. Rescanning restored V95 to > 98% for both scenarios without baseline drift, but not with additional baseline drift at 83.7%. Conclusions: The validated algorithm permits to study the effects of irregular motion and to develop and adapt appropriate motion mitigation techniques.

With rapid evolutions of fast and sophisticated calculation techniques and delivery technologies, clinics are almost facing a daily patient-specific (PS) plan adaptation, which would make a conventional experimental quality assurance (QA) workflow unlikely to be routinely feasible. Therefore, in silico approaches are foreseen by means of second-check independent dose calculation systems possibly handling machine log-files.To validate the in-house developed GPU-dose engine, FRoG, for light ion beam therapy (protons and carbon ions) as a second-check independent calculation system and to integrate machine log-file analysis into the patient-specific quality assurance (PSQA) program.Spot sizes, depth-dose distributions, and absolute dose calibrations were configured into FRoG and a set of nine regular-shaped targets in combination with more than 170 clinical treatment fields were tested against pinpoint ionization chamber measurements. Both the treatment planning system DICOM RTplans and machine treatment log-files were used as input for the dose kernel in water, and a 3D local γ (1 mm/2%) index was used as the main evaluation metric.Calculated configuration data matched experimental measurements with submillimetric agreement. For regular-shaped targets, the unsigned average relative difference between calculated and measured dose values was less than 2% for both protons and carbon ions. The mean γ passing rate (PR) was around 98% for both particle species. For clinical treatment beams, DICOM-based recalculations showed a γ-PR more than 99% for both particle species. The same level of agreement was preserved for protons when moving to log-file-based recalculations. A score of around 95% was registered for carbon ion beams, once excluding low-quality machine log-files. Unsigned average relative difference against acquired data was less than 2% also for real clinical beams.FRoG was proven as an accurate and reliable tool for PSQA in scanning light ion beam therapy. The proposed method allows for an extremely efficient workflow, without compromising the quality of the plan verification procedure.

PURPOSE In-beam Positron Emission Tomography (PET) is one of the modalities that can be used for in-vivo non-invasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy to interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in-beam PET monitoring images that can be used to locate, quantify and visualize regions with possible morphological changes occurring over the course of treatment. MATERIALS AND METHODS We selected a patient treated for Squamous Cell Carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel-wise two-tailed statistical tests of the simulated PET images, resembling the Voxel-Based Morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change. RESULTS The VBM resembling method has been successfully applied to the simulated in-beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify inter-fractional morphological changes and to visualize them superimposed on the Computed Tomography (CT) scan. In particular, the characteristic color patterns resulting from the two-tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment. CONCLUSIONS The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal inter-fractional morphological changes in patients, occurring over the course of treatment. Based on simulated in-beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments. This article is protected by copyright. All rights reserved.

The aim of this paper is to review the Dose Delivery System (DDS), developed by the National Center for Oncological Hadrontherapy (CNAO), Pavia, Italy, in collaboration with a group at the National Institute of Nuclear Physics (INFN) of Turin, Italy. The DDS controls and monitors the delivery of clinical ion beams.

Open physics 19(1), 383 - 394 (2021). doi:10.1515/phys-2021-0032, Published by de Gruyter, Berlin

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

Purpose A retrospective analysis of the dose delivery system (DDS) performances of the initial clinical operation at CNAO (Centro Nazionale di Adroterapia Oncologica) is reported, and compared with the dose delivery accuracy following the implementation of a position feedback control. Methods Log files and raw data of the DDS were analyzed for every field of patients treated with protons and carbon ions between January 2012 and April 2013 (~3800 fields). To investigate the DDS accuracy, the spot positions and the number of particles per spot measured by the DDS and prescribed by the treatment planning system were compared for each field. The impact of deviations on dose distributions was studied by comparing, through the gamma-index method, 2 three-dimensional (3D) physical dose maps (one for prescribed, one for measured data), generated by a validated dose computation software. The maximum gamma and the percentage of points with gamma ≤ 1 (passing volume) were studied as a function of the treatment day, and correlated with the deviations from the prescription in the measured number of particles and spot positions. Finally, delivered dose distributions of same treatment plans were compared before and after the implementation of a feedback algorithm for the correction of small position deviations, to study the effect on the delivery quality. A double comparison of prescribed and measured 3D maps, before and after feedback implementation, is reported and studied for a representative treatment delivered in 2012, redelivered on a polymethyl methacrylate (PMMA) block in 2018. Results Systematic deviations of spot positions, mainly due to beam lateral offsets, were always found within 1.5 mm, with the exception of the initial clinical period. The number of particles was very stable, as possible deviations are exclusively related to the quantization error in the conversion from monitor counts to particles. For the chosen representative patient treatment, the gamma-index evaluation of prescribed and measured dose maps, before and after feedback implementation, showed a higher variability of maximum gamma for the 2012 irradiation, with respect to the reirradiation of 2018. However, the 2012 passing volume is >99.8% for the sum of all fields, which is comparable to the value of 2018, with the exception of one day with 98.2% passing volume, probably related to an instability of the accelerating system. Conclusions A detailed retrospective analysis of the DDS performances in the initial period of CNAO clinical activity is reported. The spot position deviations are referable to beam lateral offset fluctuations, while almost no deviation was found in the number of particles. The impact of deviations on dose distributions showed that the position feedback implementation and the increased beam control capability acquired after the first years of clinical experience led to an evident improvement in the DDS stability, evaluated in terms of gamma-index as a measure of the impact on dose distributions. However, the clinical effect of the maximum gamma variability found in the 2012 representative irradiation is mitigated by averaging along the number of fractions, and the high percentage of passing volumes confirmed the accuracy of the delivery even before the feedback implementation.

Fast procedures for the beam quality assessment and for the monitoring of beam energy modulations during the irradiation are among the most urgent improvements in particle therapy. Indeed, the online measurement of the particle beam energy could allow assessing the range of penetration during treatments, encouraging the development of new dose delivery techniques for moving targets. Towards this end, the proof of concept of a new device, able to measure in a few seconds the energy of clinical proton beams (from 60 to 230 MeV) from the Time of Flight (ToF) of protons, is presented. The prototype consists of two Ultra Fast Silicon Detector (UFSD) pads, featuring an active thickness of 80 um and a sensitive area of 3 x 3 mm2, aligned along the beam direction in a telescope configuration, connected to a broadband amplifier and readout by a digitizer. Measurements were performed at the Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy), at five different clinical beam energies and four distances between the sensors (from 7 to 97 cm) for each energy. In order to derive the beam energy from the measured average ToF, several systematic effects were considered, Monte Carlo simulations were developed to validate the method and a global fit approach was adopted to calibrate the system. The results were benchmarked against the energy values obtained from the water equivalent depths provided by CNAO. Deviations of few hundreds of keV have been achieved for all considered proton beam energies for both 67 and 97 cm distances between the sensors and few seconds of irradiation were necessary to collect the required statistics. These preliminary results indicate that a telescope of UFSDs could achieve in a few seconds the accuracy required for the clinical application and therefore encourage further investigations towards the improvement and the optimization of the present prototype.

This paper describes the development and characterization of a Δ E-TOF detector composed of a plastic scintillator bar coupled at both ends to silicon photomultipliers. This detector is a prototype of a larger version which will be used in the FOOT (FragmentatiOn Of Target) experiment to identify the fragments produced by ion beams accelerated onto a hydrogen-enriched target. The final Δ E-TOF detector will be composed of two layers of plastic scintillator bars with orthogonal orientation and will measure, for each crossing fragment, the energy deposited in the plastic scintillator ( Δ E), the time of flight (TOF), and the coordinates of the interaction position in the scintillator. To meet the FOOT experimental requirements, the detector should have energy resolution of a few percents and time resolution of 70 ps, and it should allow to discriminate multiple fragments belonging to the same event. To evaluate the achievable performances, the detector prototype was irradiated with protons of kinetic energy in the 70–230 MeV range and interacting at several positions along the bar. The measured energy resolution σ Δ E ∕ Δ E was 6–14%, after subtracting the fluctuations of the deposited energy. A time resolution σ between 120 and 180 ps was obtained with respect to a trigger detector. A spatial resolution σ of 1.9 cm was obtained for protons interacting at the center of the bar.

In hadron therapy, the accelerated ions, interacting with the body of the patient, cause the fragmentation of both projectile and target nuclei. The fragments interact with the human tissues depositing energy both in the entrance channel and in the volume surrounding the tumor. The knowledge of the fragments features is crucial to determine the energy amount deposited in the human body, and - hence - the damage to the organs and to the tissues around the tumor target. The FOOT (FragmentatiOn Of Target) experiment aims at studying the fragmentation induced by the interaction of a proton beam (150-250 MeV/n) inside the human body. The FOOT detector includes an electronic setup for the identification of Z ≥ 3 fragments integrated with an emulsion spectrometer to measure Z ≤ 3 fragments. Charge identification by nuclear emulsions is based on the development of techniques of controlled fading of the particle tracks inside the nuclear emulsion, that extend the dynamical range of the films developed for the tracking of minimum ionising particles. The controlled fading strongly depends on temperature, relative humidity and treatment duration. In this study the performances in terms of charge separation of proton, helium and carbon particles, obtained on a batch of new emulsion films produced in Japan are reported.

Particle therapy exploits the energy deposition pattern of hadron beams. The narrow Bragg Peak at the end of range is a major advantage but range uncertainties can cause severe damage and require online verification to maximise the effectiveness in clinics. In-beam Positron Emission Tomography (PET) is a non-invasive, promising in-vivo technique, which consists in the measurement of the β+ activity induced by beam-tissue interactions during treatment, and presents the highest correlation of the measured activity distribution with the deposited dose, since it is not much influenced by biological washout. Here we report the first clinical results obtained with a state-of-the-art in-beam PET scanner, with on-the-fly reconstruction of the activity distribution during irradiation. An automated time-resolved quantitative analysis was tested on a lacrimal gland carcinoma case, monitored during two consecutive treatment sessions. The 3D activity map was reconstructed every 10 s, with an average delay between beam delivery and image availability of about 6 s. The correlation coefficient of 3D activity maps for the two sessions (above 0.9 after 120 s) and the range agreement (within 1 mm) prove the suitability of in-beam PET for online range verification during treatment, a crucial step towards adaptive strategies in particle therapy.

Purpose Unlike currently used gas ionization chambers, solid state detectors offer large granularity and sensitivity to single incoming particles, therefore being ideally suited to improve the present technology for beam monitoring in particle therapy. However, several drawbacks, such as radiation damage, prevented their use so far on high flux therapeutic beams. Two prototype devices for monitoring particle beams are under development, based on innovative silicon low-gain avalanche detectors optimized for time resolution (Ultra Fast Silicon Detectors – UFSDs). Preliminary results with proton beams are presented. Methods UFSDs are low-gain avalanche detectors optimized for time resolution, where sensors as thin as 50 μ m provide signals of ∼ 1 ns time duration with time resolutions of tenths of ps, and large enough signal-to-noise ratio to efficiently discriminate proton signal. One prototype device is being developed to directly count individual protons at high rates, while a second one is under investigation to measure the beam energy with time-of-flight techniques. This requires the design of custom UFSD sensors as well VLSI readout electronics. From simulations’ results and first beam tests with UFSD pads, strip detectors were produced, with two geometries (30 mm and 15 mm length) and different doping modalities to improve radiation hardness. In parallel, prototypes of a new readout chip have been submitted to the foundry. Results Strips sensors were characterized in the laboratory through laser test and I(V) curve studies, and a test with a therapeutic proton beam, with energy ranging from 62 to 227 MeV, was done. Results were obtained via offline analysis of the collected waveforms for Boron and Gallium doped sensors. Time resolution of 35 ps, signal duration of ns, and good S/N separation were found. A gain degradation of 20% was founded in single pad sensors after 10 12 protons/cm2 irradiation. Pile-up effects are under investigation. Conclusions Based on the preliminary results, UFSDs are found to be a promising improvement of monitor chamber. The aim of this contribution is to review the advancement of the project and to report on the results of the test of UFSD strip sensors with a therapeutic proton beam.

Dynamic intensity-modulated radiotherapy (D-IMRT) using the sliding-window technique is currently applied for selected treatments of head and neck cancer at Institute for Cancer Research and Treatment of Candiolo (Turin, Italy). In the present work, a PiXel-segmented ionization Chamber (PXC) has been used for the verification of 19 fields used for four different head and neck cancers. The device consists of a 32 × 32 matrix of 1024 parallel-plate ionization chambers arranged in a square of 24 × 24 cm2 area. Each chamber has 0.4 cm diameter and 0.55 cm height; a distance of 0.75 cm separates the centre of adjacent chambers. The sensitive volume of each single ionization chamber is 0.07 cm3. Each of the 1024 independent ionization chambers is read out with a custom microelectronics chip.The output factors in water obtained with the PXC at a depth of 10 cm were compared to other detectors and the maximum difference was 1.9% for field sizes down to 3 × 3 cm2. Beam profiles for different field dimensions were measured with the PXC and two other types of ionization chambers; the maximum distance to agreement (DTA) in the 20–80% penumbra region of a 3 × 3 cm2 field was 0.09 cm. The leaf speed of the multileaf collimator was varied between 0.07 and 2 cm s−1 and the detector response was constant to better than 0.6%. The behaviour of the PXC was measured while varying the dose rate between 0.21 and 1.21 Gy min−1; the mean difference was 0.50% and the maximum difference was 0.96%. Using fields obtained with an enhanced dynamic wedge and a staircase-like (step) IMRT field, the PXC has been tested for simple 1D modulated beams; comparison with film gave a maximum DTA of 0.12 cm. The PXC was then used to check four different IMRT plans for head and neck cancer treatment: cervical chordoma, parotid, ethmoid and skull base. In the comparison of the PXC versus film and PXC versus treatment planning system, the number of pixels with γ parameter ≤1 was 97.7% and 97.6%, respectively.

In hadron therapy one of the most advanced methods for beam delivery is the active scanning technique which uses fast scanning magnets to drive a narrow particle beam across the target. The Centro Nazionale di Adroterapia Oncologica (CNAO) will treat tumours with this technique. The CNAO scanning system includes two identical dipole magnets for horizontal and vertical beam deflection, each one connected to a fast power supply. The dose delivery system exploits a set of monitor chambers to measure the fluence and position of the beam and drives the beam during the treatment by controlling the sequence of currents set by the power supplies. A test of the dynamic performance of the scanning system has been performed using a Hall probe to measure the field inside the magnet and the results are presented in this paper.

The therapeutic use of protons and ions, especially carbon ions, is a new technique and a challenge to conform the dose to the target due to the energy deposition characteristics of hadron beams. An appropriate treatment planning system (TPS) is strictly necessary to take full advantage. We developed a TPS software, ANCOD++, for the evaluation of the optimal conformal dose. ANCOD++ is an analytical code using the voxel-scan technique as an active method to deliver the dose to the patient, and provides treatment plans with both proton and carbon ion beams. The iterative algorithm, coded in C++ and running on Unix/Linux platform, allows the determination of the best fluences of the individual beams to obtain an optimal physical dose distribution, delivering a maximum dose to the target volume and a minimum dose to critical structures. The TPS is supported by Monte Carlo simulations with the package GEANT3 to provide the necessary physical lookup tables and verify the optimized treatment plans. Dose verifications done by means of full Monte Carlo simulations show an overall good agreement with the treatment planning calculations. We stress the fact that the purpose of this work is the verification of the physical dose and a next work will be dedicated to the radiobiological evaluation of the equivalent biological dose.

Segmented ionization chambers represent a good solution to monitor the position, the intensity and the shape of ion beams in hadrontherapy. Pixel and strip chambers have been developed for both passive scattering and active scanning dose delivery systems. In particular, strip chambers are optimal for pencil beam scanning, allowing for spatial and time resolutions below 0.1 mm and 1 ms, respectively. The MATRIX pixel and the Strip Accurate Monitor for Beam Applications (SAMBA) detectors are described in this paper together with the results of several beam tests and industrial developments based on these prototypes.

The study that we present is part of the preparation work for the setup of the FOOT (FragmentatiOn Of Target) experiment whose main goal is the measurement of the double differential cross sections of fragments produced in nuclear interactions of particles with energies relevant for particle therapy. The present work is focused on the characterization of the gas-filled drift chamber detector composed of 36 sensitive cells, distributed over two perpendicular views. Each view consists of six consecutive and staggered layers with three cells per layer. We investigated the detector efficiency and we performed an external calibration of the space–time relations at the level of single cells. This information was then used to evaluate the drift chamber resolution. An external tracking system realized with microstrip silicon detectors was adopted to have a track measurement independent on the drift chamber. The characterization was performed with a proton beam at the energies of 228 and 80 MeV. The overall hit detection efficiency of the drift chamber has been found to be 0 . 929 ± 0 . 008 , independent on the proton beam energy. The spatial resolution in the central part of the cell is about 150 ± 10 μ m and 300 ± 10 μ m and the corresponding detector angular resolution has been measured to be 1 . 62 ± 0 . 16 mrad and 2 . 1 ± 0 . 4 mrad for the higher and lower beam energies, respectively. In addition, the best value on the intrinsic drift chamber resolution has been evaluated to be in the range 60 − 100 μ m. In the framework of the FOOT experiment, the drift chamber will be adopted in the pre-target region, and will be exploited to measure the projectile direction and position, as well as for the identification of pre-target fragmentation events.