Management of Motion and Anatomical Variations in Charged Particle Therapy:Past, Present, and Into the Future

The major aim of radiation therapy is to provide curative or palliative treatment to cancerous malignancies while minimizing damage to healthy tissues. Charged particle radiotherapy utilizing carbon ions or protons is uniquely suited for this task due to its ability to achieve highly conformal dose distributions around the tumor volume. For these treatment modalities, uncertainties in the localization of patient anatomy due to inter- and intra-fractional motion present a heightened risk of undesired dose delivery. A diverse range of mitigation strategies have been developed and clinically implemented in various disease sites to monitor and correct for patient motion, but much work remains. This review provides an overview of current clinical practices for inter and intra-fractional motion management in charged particle therapy, including motion control, current imaging and motion tracking modalities, as well as treatment planning and delivery techniques. We also cover progress to date on emerging technologies including particle-based radiography imaging, novel treatment delivery methods such as tumor tracking and FLASH, and artificial intelligence and discuss their potential impact towards improving or increasing the challenge of motion mitigation in charged particle therapy

Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel

Background: Ion beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT). Materials and methods: The robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90Rectum), respectively. Results: The application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively. Conclusions: The dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal exposure to high treatment dose and, therefore, can reduce the hazard of rectal toxicity in ion beam therapy of PC. The results of this study enable modifications of the PC ion therapy protocol such as dose escalation or hypofractionation

Monitoring of hadrontherapy treatments by means of charged particle detection

The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages

Clinical practice vs. state-of-the-art research and future visions:Report on the 4D treatment planning workshop for particle therapy - Edition 2018 and 2019

The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively. This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field

GPU accelerated Monte Carlo scoring of positron emitting isotopes produced during proton therapy for PET verification.

Objective.Verification of delivered proton therapy treatments is essential for reaping the many benefits of the modality, with the most widely proposedin vivoverification technique being the imaging of positron emitting isotopes generated in the patient during treatment using positron emission tomography (PET). The purpose of this work is to reduce the computational resources and time required for simulation of patient activation during proton therapy using the GPU accelerated Monte Carlo code FRED, and to validate the predicted activity against the widely used Monte Carlo code GATE.Approach.We implement a continuous scoring approach for the production of positron emitting isotopes within FRED version 5.59.9. We simulate treatment plans delivered to 95 head and neck patients at Centrum Cyklotronowe Bronowice using this GPU implementation, and verify the accuracy using the Monte Carlo toolkit GATE version 9.0.Main results.We report an average reduction in computational time by a factor of 50 when using a local system with 2 GPUs as opposed to a large compute cluster utilising between 200 to 700 CPU threads, enabling simulation of patient activity within an average of 2.9 min as opposed to 146 min. All simulated plans are in good agreement across the two Monte Carlo codes. The two codes agree within a maximum of 0.95σon a voxel-by-voxel basis for the prediction of 7 different isotopes across 472 simulated fields delivered to 95 patients, with the average deviation over all fields being 6.4 × 10-3σ.Significance.The implementation of activation calculations in the GPU accelerated Monte Carlo code FRED provides fast and reliable simulation of patient activation following proton therapy, allowing for research and development of clinical applications of range verification for this treatment modality using PET to proceed at a rapid pace

Intraoperative probe detecting β− decays in brain tumour radio-guided surgery

Abstract Radio-guided surgery (RGS) is a technique to intraoperatively detect tumour remnants, favouring a radical resection. Exploiting β − emitting tracers provides a higher signal to background ratio compared to the established technique with γ radiation, allowing the extension of the RGS applicability range. We developed and tested a detector based on para-terphenyl scintillator with high sensitivity to low energy electrons and almost transparent to γ s to be used as intraoperative probe for RGS with β − emitting tracer. Portable read out electronics was customised to match the surgeon needs. This probe was used for preclinical test on specific phantoms and a test on "ex vivo" specimens from patients affected by meningioma showing very promising results for the application of this new technique on brain tumours. In this paper, the prototype of the intraoperative probe and the tests are discussed; then, the results on meningioma are used to make predictions on the performance of the probe detecting residuals of a more challenging and more interesting brain tumour: the glioma

ProTheRaMon : a GATE simulation framework for proton therapy range monitoring using PET imaging

Objective. This paper reports on the implementation and shows examples of the use of the ProTheRaMon framework for simulating the delivery of proton therapy treatment plans and range monitoring using positron emission tomography (PET). ProTheRaMon offers complete processing of proton therapy treatment plans, patient CT geometries, and intra-treatment PET imaging, taking into account therapy and imaging coordinate systems and activity decay during the PET imaging protocol specific to a given proton therapy facility. We present the ProTheRaMon framework and illustrate its potential use case and data processing steps for a patient treated at the Cyclotron Centre Bronowice (CCB) proton therapy center in Krakow, Poland. Approach. The ProTheRaMon framework is based on GATE Monte Carlo software, the CASToR reconstruction package and in-house developed Python and bash scripts. The framework consists of five separated simulation and data processing steps, that can be further optimized according to the user’s needs and specific settings of a given proton therapy facility and PET scanner design. Main results. ProTheRaMon is presented using example data from a patient treated at CCB and the J-PET scanner to demonstrate the application of the framework for proton therapy range monitoring. The output of each simulation and data processing stage is described and visualized. Significance. We demonstrate that the ProTheRaMon simulation platform is a high-performance tool, capable of running on a computational cluster and suitable for multi-parameter studies, with databases consisting of large number of patients, as well as different PET scanner geometries and settings for range monitoring in a clinical environment. Due to its modular structure, the ProTheRaMon framework can be adjusted for different proton therapy centers and/or different PET detector geometries. It is available to the community via github (Borys et al 2022)