Abstract ID: 139 Monte Carlo simulations for imaging in proton therapy

There is an increased interest in developing imaging systems in proton therapy, with the aim of reducing range uncertainty in treatment planning, assisting in patient positioning and verifying anatomical changes at the time of the treatment. Recently, the PRaVDA collaboration has developed two different solid-state detector technologies for imaging in proton therapy: Silicon Strip Detectors and CMOS Active Pixel Sensors (APSs). This paper reports on the design and optimisation process of the PRaVDA CMOS APSs. Optimisation of parameters, such as epitaxial thickness and resistivity, and performance for individual proton detection and proton radiography are reported.

ALICE (A Large Ion Collider Experiment) is the heavy-ion experiment at the Large Hadron Collider (LHC) at CERN. As an important part of its upgrade plans, the ALICE experiment will schedule the installation of a new Inner Tracking System (ITS) during the Long Shutdown 2 (LS2) of the LHC. The new ITS layout will consist of seven concentric layers, $\approx$ 12.5 Gigapixel camera covering about 10m$^2$ with Monolithic Active Pixel Sensors (MAPS). This choice of technology has been guided by the tight requirements on the material budget of 0.3$\%$ X/X$_0$ per layer for the three innermost layers and backed by the significant progress in the field of MAPS in recent years. The technology initially chosen for the ITS upgrade is the TowerJazz 180 nm CMOS Technology. It offers a standard epitaxial layer of 15 - 18 $\mu$m with a resistivity between 1 and 5 k$\Omega$~cm$^{-1}$ and a gate oxide thickness below 4 nm, thus being more robust to Total Ionizing Dose (TID). The main subject of this thesis is to implement a novel digital pixel readout architecture for MAPS. This thesis aims to study this novel readout architecture as an alternative to the rolling-shutter readout. However, this must be investigated through the study of several chip readout architectures during the R$\&$D phase. Another objective of this thesis is the study and characterization of TowerJazz, if it meets the Non-Ionizing Energy Loss (NIEL) and Single Event Effects (SEE) of the ALICE ITS upgrade program. Other goals of this thesis are: Implementation of the top-down flow for this CMOS process and the design of multiple readouts for different prototypes up to the assembly of a full-scale prototype. Characterization of the radiation hardness and SEE of the chips submitted to fabrication. Characterization of full custom designs using analog simulations and the generation of digital models for the simulation chain needed for the verification process. \item Implementation and study of different digital readouts to meet the ITS upgrade program in integration time, pixel size and power consumption, from the conceptual idea, production and fabrication phase. SChapter 1 is a brief overview of CERN, the LHC and the detectors complex. The ALICE ITS will be explained, focusing on the ITS upgrade in terms of detector needs and design constraints. Chapter 2 explains the properties of silicon detectors and the detector material and the principles of operation for MAPS. Chapters 3 and 4 describe the ALPIDE prototypes and their readout based on MAPS; this forms the central part of this work, including the multiple families of pixel detectors fabricated in order to reach the final design for the ITS. The ALPIDE3/pALPIDE3B chip, the latest MAPS chip designed, will be explained in detail, as well focusing in the matrix digital readout. In chapter 5 the noise measurements and its characterization are presented including a brief summary of detector response to irradiation with soft X-rays, sources and particle beams. on the ITS upgrade in terms of detector needs and design constraints. Chapter 2 explains the properties of silicon detectors and the detector material and the principles of operation for MAPS. Chapters 3 and 4 describe the ALPIDE prototypes and their readout based on MAPS; this forms the central part of this work, including the multiple families of pixel detectors fabricated in order to reach the final design for the ITS. The ALPIDE3/pALPIDE3B chip, the latest MAPS chip designed, will be explained in detail, as well focusing in the matrix digital readout. In chapter 5 the noise measurements and its characterization are presented including a brief summary of detector response to irradiation with soft X-rays, sources and particle beams.

Ion therapy guideline (Version 2020)

Purpose:X‐ray system is commonly used for IGRT in proton therapy, however image acquisition not only increases treatment time but also adds imaging dose. We studied a 3D surface camera system (AlignRT) performance for proton therapy.Methods:System accuracy was evaluated with rigid phantom under two different camera location configurations. For initial clinical applications, post mastectomy chest wall and partial breast treatments were studied. X‐ray alignment was used as our ground truth. Our studies included: 1) comparison of daily patient setup shifts between X‐ray alignment and SI calculation; 2) interfractional breast surface position variation when aligning to bony landmark on X‐ray; 3) absolute positioning using planning CT DICOM data; 4) shifts for multi‐isocenter treatment plan; 5) couch isocentric rotation accuracy.Results:Camera locations affected the system performance. After camera relocation, the accuracy of the system for the rigid phantom was within 1 mm (fixed couch), and 1.5 mm (isocentric rotation). For intrafractional patient positioning, X‐ray and AlignRT shifts were highly correlated (r=0.99), with the largest difference (mean ± SD) in the longitudinal direction (2.14 ± 1.02 mm). For interfractional breast surface variation and absolute positioning, there were still larger disagreements between the two modalities due to different focus on anatomical landmarks, and 95% of the data lie within 5mm with some outliers at 7 mm–9 mm. For multi‐isocenter shifts, the difference was 1 ± 0.56 mm over an 11 cm shift in longitudinal direction. For couch rotation study, the differences was 1.36 ± 1.0 mm in vertical direction, 3.04 ± 2.11 mm in longitudinal direction, and 2.10 ± 1.66 mm in lateral direction, with all rotation differences < 1.5 degree.Conclusion:Surface imaging is promising for intrafractional treatment application in proton therapy to reduce X‐ray frequency. However the interfractional discrepancy between the X‐ray and SI requires future validation.

Development of a silver-doped zinc sulfide incorporated wearable fabric for proton beam surface imaging.

The principal aim of the AEgIS experiment at CERN is to measure the acceleration of antihydrogen due to Earth's gravitational field. This would be a test of the Weak Equivalence Principle, which states that all bodies fall with the same acceleration independently of their mass and composition. The effect of Earth's gravitational field on antimatter will be determined by measuring the deflection of the path of the antihydrogen from a straight line. The position of the antihydrogen will be found by detecting its annihilation on the surface of a silicon detector. The gravitational measurement in AEgIS will be performed with a gravity module, which includes the silicon detector, an emulsion detector and a scintillating fibre time-of-flight detector. As the experiment attempts to determine the gravitational acceleration with a precision of 1%, a position resolution better than 10 μm is required. Here we present the results of a study of antiproton annihilations in a 3D silicon pixel sensor and compare the results with a previous study using a monolithic active pixel sensor. This work is part of a larger study on different silicon sensor technologies needed for the development of a silicon position detector for the AEgIS experiment. The 3D detector together with its readout electronics have been originally designed for the ATLAS detector at the LHC. The direct annihilation of low energy antiprotons ( ~ 100 keV) takes place in the first few μm of the silicon sensor and we show that the charged products of the annihilation can be detected with the same sensor. The present study also aims to understand the signature of an antiproton annihilation event in segmented silicon detectors and compares it with a GEANT4 simulation model. These results will be used to determine the geometrical and process parameters to be adopted by the silicon annihilation detector to be installed in AEgIS.

BackgroundLow and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours.Methods/DesignThe study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial.Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points.DiscussionUp to now it was impossible to compare two different particle therapies, i.e. protons and carbon ions, directly at the same facility in connection with the treatment of low grade skull base chondrosarcomas.This trial is a phase III study to demonstrate that carbon ion radiotherapy (experimental treatment) is not relevantly inferior and at least as good as proton radiotherapy (standard treatment) with respect to 5 year LPFS in the treatment of chondrosarcomas. Additionally, we expect less toxicity in the carbon ion treatment arm.Trial RegistrationClinicalTrials.gov identifier: NCT01182753

The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT). We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes. After a median follow-up of 44 (range, 6-87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients. Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC. • Proton and carbon ion therapy are effective and safe in skull base chordoma.• Prognostic factors are GTV, organs at risk compression, and dose coverage.• Dual particle therapy and customized strategy was adopted.

We present experimental investigation of cross sections for processes crucial in view of prompt-gamma imaging. The prompt-gamma rays were produced from an interaction of a proton beam with different phantom materials composed of carbon, oxygen and hydrogen. The used target setup allowed precise selection of the investigated depth in the phantom. We studied details of the dependence of prompt-gamma yields on beam energy, detection angle and elemental composition of irradiated phantom. The analysis was focused on the discrete transitions with the largest cross sections: 4.44 MeV in 12C and 6.13 MeV in 16O. The results are presented in form of profiles of the prompt-gamma yield as a function of depth. They are compared to calculations including different cross-section models. Obtained results are in agreement with the model exploiting cross-section data collected from the literature, but the comparison with the TALYS model shows discrepancies. In the latest experiment, special attention was paid to the shape of the distal fall-off. The width of that fall-off is directly linked to the resolution of prompt-gamma based methods of range verification. Preliminary results on the beam-energy dependence of this quantity are presented.

The ALICE collaboration is planning to replace its innermost tracking layers during the Large Hadron Collider (LHC) Long Shutdown 3 with a novel detector that will be as close as 18 mm to the interaction point and as thin as <0.05%X 0 per layer. To achieve these numbers, a wafer-scale Monolithic Active Pixel Sensor (MAPS) in 65 nm technology is being developed. This sensor, fabricated on 300 mm wafers, will reach dimensions of up to 280 mm by 94 mm. Sensors are subsequently thinned down to values between 20 μm to 40 μm, where they become flexible and are bent into truly cylindrical half-barrels.Following the publication of a Letter of Intent by ALICE and the endorsement by the Large Hadron Collider Committee (LHCC) end of 2019, a very active research and development programme on bent silicon detectors has started.This contribution reviews the detector concept, the physics motivations, and lays out the R&D path. Mechanical integration tests with ultra-thin silicon wafers as well as electrical test of bent MAPS, including beam test results, will be shown and demonstrate the feasibility of this new class of tracking detectors.

BackgroundStereotactic radiotherapy (SRT) and Proton therapy (PT) are both options in the management of liver lesions. Limited clinical-dosimetric comparison are available. Moreover, dose-constraint routinely used in liver PT and SRT considers only the liver spared, while optimization strategies to limit the liver damaged are poorly reported.MethodsPrimary endpoint was to assess and compare liver sparing of four contemporary RT techniques. Secondary endpoints were freedom from local recurrence (FFLR), overall survival (OS), acute and late toxicity. We hypothesize that Focal Liver Reaction (FLR) is determined by a similar biologic dose. FLR was delineated on follow-up MRI. Mean C.I. was computed for all the schedules used. A so-called Fall-off Volume (FOV) was defined as the area of healthy liver (liver-PTV) receiving more than the isotoxic dose. Fall-off Volume Ratio (FOVR) was defined as ratio between FOV and PTV.Results213 lesions were identified. Mean best fitting isodose (isotoxic doses) for FLR were 18Gy, 21.5 Gy and 28.5 Gy for 3, 5 and 15 fractions. Among photons, an advantage in terms of healthy liver sparing was found for Vmat FFF with 5mm jaws (p = 0.013) and Cyberknife (p = 0.03). FOV and FOVR resulted lower for PT (p < 0.001). Three years FFLR resulted 83%. Classic Radiation induced liver disease (RILD, any grade) affected 2 patients.ConclusionsCyberknife and V-MAT FFF with 5mm jaws spare more liver than V-MAT FF with 10 mm jaws. PT spare more liver compared to photons. FOV and FOVR allows a quantitative analysis of healthy tissue sparing performance showing also the quality of plan in terms of dose fall-off.

IntroductionA broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer....

Radiation therapy (RT) plays a fundamental role in the treatment of malignant and benign brain tumors. Current state-of-the-art photon- and proton-based RT combines more conformal dose distribution of target volumes and accurate dose delivery while limiting the adverse radiation effects. PubMed was systematically searched from from 2000 to October 2023 to identify studies reporting outcomes related to treatment of central nervous system (CNS)/skull base tumors with PT in adults. Several studies have demonstrated that proton therapy (PT) provides a reduced dose to healthy brain parenchyma compared with photon-based (xRT) radiation techniques. However, whether dosimetric advantages translate into superior clinical outcomes for different adult brain tumors remains an open question. This review aims at critically reviewing the recent studies on PT in adult patients with brain tumors, including glioma, meningiomas, and chordomas, to explore its potential benefits compared with xRT.

Single Institution Experience of Proton and Photon-based Postoperative Radiation Therapy for Non–small-cell Lung Cancer

Nuclear reactions between proton irradiation and boron via p + 11B→3α (boron proton-capture reaction; BPCR) and n + 10B→α+7Li (boron neutron-capture reaction; BNCR) enhance the cell-killing effects of proton beam irradiation (PBI); however, which reaction exerts superior sensitization effects remains unclear. Therefore, we evaluated the efficacy of the BPCR and BNCR in enhancing the cell-killing effects of PBI. Human osteosarcoma (MG-63) and glioma (U-251 MG) cells were irradiated with PBI with and without boronophenylalanine (BPA) enriched with > 95% 10B (10B-BPA) for BNCR and BPA with natural isotopic abundance of boron (80% 11B + 20% 10B; N-BPA) for BPCR. Sensitizer enhancement ratios (SERs) were obtained by comparing the doses that yielded a surviving fraction of 10% (D10). The D10 values for PBI alone, PBI with 10B-BPA, and PBI with N-BPA were 5.67, 4.85, and 5.51 and 5.21, 4.65, and 5.18 for MG-63 and U-251 MG cells, respectively. SERs of PBI with 10B-BPA and N-BPA were 1.17 and 1.03 and 1.12 and 1.01 for MG-63 and U-251 MG cells, respectively. Our results indicate that 10B-BPA-associated BNCR may be a better sensitizer for PBI than N-BPA-associated BPCR, which warrants further investigation into the clinical use of 10B-enriched BPA.