Proton Therapy Research Articles

LET-based approximation of the microdosimetric kinetic model for proton radiotherapy.

Phenomenological relative biological effectiveness (RBE) models for proton therapy, based on the dose-averaged linear energy transfer (LET), have been developed to address the apparent RBE increase towards the end of the proton range. The results of these phenomenological models substantially differ due to varying empirical assumptions and fitting functions. In contrast, more theory-based approaches are used in carbon ion radiotherapy, such as the microdosimetric kinetic model (MKM). However, implementing microdosimetry-based models in LET-based proton therapy treatment planning systems poses challenges. This work presents a LET-based version of the MKM that is practical for clinical use in proton radiotherapy. At first, we derived an approximation of the Mayo Clinic Florida (MCF) MKM for relatively-sparsely ionizing radiation such as protons. The mathematical formalism of the proposed model is equivalent to the original MKM, but it maintains some key features of the MCF MKM, such as the determination of model parameters from measurable cell characteristics. Subsequently, we carried out Monte Carlo calculations with PHITS in different simulated scenarios to establish a heuristic correlation between microdosimetric quantities and the dose averaged LET of protons. A simple allometric function was found able to describe the relationship between the dose-averaged LET of protons and the dose-mean lineal energy, which includes the contributions of secondary particles. The LET-based MKM was used to model the in vitro clonogenic survival RBE of five human and rodent cell lines (A549, AG01522, CHO, T98G, and U87) exposed to pristine and spread-out Bragg peak (SOBP) proton beams. The results of the LET-based MKM agree well with the biological data in a comparable or better way with respect to the other models included in the study. A sensitivity analysis on the model results was also performed. The LET-based MKM integrates the predictive theoretical framework of the MCF MKM with a straightforward mathematical description of the RBE based on the dose-averaged LET, a physical quantity readily available in modern treatment planning systems for proton therapy.

Development of an algorithm for proton dose calculation in magnetic fields.

The advantages of proton therapy can be further enhanced with online magnetic resonance imaging (MRI) guidance. One of the challenges in the realization of MRI-guided proton therapy (MRPT) is accurately calculating the radiation dose in the presence of magnetic fields. This study aims to develop an efficient and accurate proton dose calculation algorithm adapted to the presence of magnetic fields. An analytical-numerical radiation dose calculation algorithm, Proton and Ion Dose Engine (PRIDE), was developed. The algorithm combines the pencil beam algorithm (PBA) with a novel iterative voxel-based ray-tracing algorithm. The new ray-tracing method uses fewer assumptions and ensures broader applicability for proton beam trajectory prediction in magnetic fields, and has been compared to Wolf's method and Schellhammer's method. The accuracy of PRIDE algorithm was validated on three phantoms and two practical plans (one single-field water plan and one prostate tumor plan) in different magnetic field strengths up to 3.0 T. The validation was performed by comparing the results against the Monte Carlo (MC) simulations, using the global gamma index criteria of 2%/2mm and 3%/3mm with a 10% threshold. PRIDE showed good agreement with MC in homogeneous and slab heterogeneous phantom, achieving gamma passing rates (%GPs) above 99% for 2%/2mm criteria when magnetic field strength is not greater than 1.5 T. Although the agreement decreased for scenarios involving high proton energy (240 MeV) and strong magnetic field (3.0 T), the 2%/2mm %GPs still remained above 98%. In lateral heterogeneous phantom, the accuracy of PRIDE decreased due to the PBA's limitation. For the two practical plans in different magnetic fields, %GPs exceeded 98% and 99% for 2%/2mm and 3%/3mm criteria, respectively. PRIDE can perform efficient and accurate proton dose calculation in magnetic fields up to 3.0 T, and is expected to work as a useful tool for proton dose calculation in MRPT.

Advanced radiation therapy options for primary and metastatic spine tumors

Primary spinal cord and metastatic spine tumors represent a heterogenous group of malignancies whose management is complex given the variety of tumor histologies, tumor-related morbidity, and potential complications of treatment. The critical role of radiation therapy in the management of primary spinal cord and metastatic spine tumors has been influenced by advances in neurosurgical techniques, neuroimaging, integrative diagnoses, and most impactfully through advances in radiotherapy technology specifically stereotactic radiotherapy and proton therapy. This article reviews contemporary literature supporting the use of advanced radiotherapy in the management of primary spinal cord and metastatic spine tumors.

Monte Carlo study of microdosimetric spectra conversion from diamond to tissue in proton therapy

Diamond is regarded as a promising material in microdosimetry. However, since the stopping power of the diamond is different from tissue, the energy deposition distribution in the diamond is not identical to that in tissue. Therefore, a conversion of the spectra in the diamond microdosimeter to the tissue site is needed. In this work, we introduced a method for the tissue equivalence conversion of diamond microdosimeters, which is developed to perform the energy deposition spectra conversion from the diamond to an equivalent size of tissue in radiotherapy. It was derived from the scaled Fourier transformation and the scaling factor. The method was tested by comparing the spectra converted from the diamond to tissue with those obtained in tissue along the Bragg curve at different locations. The results show that: i) the conversion method can overcome the defect of poor coincidence of the spectra between converted and actual results in low deposition energy zones, which is introduced by the method derived based on the distribution characteristics; ii) The equivalence between detector material and target tissue can affect the conversion results at the plateau of the Bragg curve; iii) The inconsistency between the converted and actual spectra due to the spectra shapes was also found, which occurs in the range of η from 0.117 to 1.248 for diamonds in this work; iv) the conversion at the distal part of the Bragg peak should pay attention to the range of the incident particles and the diamond microdosimeter size. To sum up, the method introduced in this work shows relatively good results in microdosimetric spectra conversion from diamond to tissue, especially in low-energy deposition regions. Nonetheless, further study is necessary to improve the practicability of this method so that it can be competent for spectral conversion on the whole Bragg curve.

Performance of a BeO-based dosimetry system for proton and electron beam dose measurements

This study aims to evaluate the performance of the BeO-based myOSLchip system (RadPro International GmbH, Remscheid, Germany) for dosimetry of proton and electron radiotherapy beams. Although beryllium oxide (BeO) has been recognised as a promising material for luminescence dosimetry in radiotherapy, this research extends beyond material properties and examines the entire BeO-based dosimetry system, including the detector, holder, and readout components.Packages of myOSLchip detectors were irradiated either in a (70−230) MeV proton beam or in a 16 MeV electron beam. The readouts were carried out using the portable myOSLchip reader. In the electron beam, tests on the precision, dose response up to 100 Gy and dose-rate effects of the system were carried out. In the proton beam, the system was tested for its dose response (up to 10 Gy), fading, and linear energy transfer (LET) response.For proton irradiations, the myOSLchip BeO OSLDs exhibited stability within 2 % over 135 days, as well as a linear dose response in the tested range, (0.1−10) Gy. The efficiency showed a reduction for proton beams with LET values (for water) above 0.6 keV/μm, with up to 40 % loss in efficiency at 4 keV/μm. For the electron irradiations, they showed a linear dose–response up to 20 Gy and dose-rate independence, with a constant response at least up to 2.99×105 Gy s−1. Using individual chip sensitivity correction, the precision for a single chip was around 3.5% (standard deviation of the data of all chips) and for a package comprising four chips was 1.7% (standard deviation of the mean of the four chips).These findings suggest the myOSLchip system’s potential as a reliable alternative to existing dosimetry systems in clinical applications.

399 - Comparison of image-guidance in proton and photon radiation therapy: Preliminary clinical experience

399 - Comparison of image-guidance in proton and photon radiation therapy: Preliminary clinical experience

7910 Hypopituitarism Incidence Following Proton Beam Radiotherapy for Treatment of Chordomas and Parasellar Meningiomas

7910 Hypopituitarism Incidence Following Proton Beam Radiotherapy for Treatment of Chordomas and Parasellar Meningiomas

Comparing robust proton versus online adaptive photon radiotherapy for short-course treatment of rectal cancer

Background and purposeImage-guided proton beam therapy (IG-PBT) and cone-beam CT (CBCT)-based online adaptive photon radiotherapy (oART) have potentials to restrict radiation toxicity. They are both hypothesised to reduce therapy limiting bowel toxicity in the multimodality treatment of locally advanced rectal cancer (LARC). This study aimed to quantify the difference in relevant dose-volume metrics for these modalities. Material and MethodsSix-degrees-of-freedom IG-PBT and oART short-course radiotherapy (SCRT) were simulated for 18 LARC patients. Relative biological effectiveness (RBE) was 1.1 for IG-PBT. Delivered dose was evaluated using post-CBCTs. Target coverage was considered robust if average dose to 99 % of the clinical target volume was ≥ 95 % of the prescription. Organ at risk (OAR) doses were compared using dose-volume histograms and severe bowel toxicity estimated using dose–response modelling. ResultsTarget coverage was robust in all patients for oART and all but one patient for IG-PBT. For the main OARs, IG-PBT increased the volume exposed to ≥ 15 Gy (RBE), but reduced volumes exposed to lower doses. Both low- and high-dose exposure to bowel loops were significantly different between the modalities (median (interquartile range) IG-PBT-V8.9Gy(RBE) = 92 cm3 (51–156), oART-V8.9Gy(RBE) = 166 cm3 (107–234), p < 0.001; IG-PBT-V23Gy(RBE) = 62 cm3 (25–106), oART-V23Gy(RBE) = 38 cm3 (18–75), p < 0.001), translating into similar total grade ≥ 3 bowel toxicity risk. ConclusionIG-PBT and oART delivered comparable and satisfying target coverage in SCRT for LARC with similar estimated risk of severe bowel toxicity. Volumes of OAR exposed to 15 Gy (RBE) or more were reduced by oART, while IG-PBT reduced the volumes receiving doses below this level.

From dark matter searches to proton therapy: Measuring target fragmentation with nanometric nuclear emulsions

The DAMON (Direct meAsureMent of target fragmentatiON) project aims to explore the use of Nano Imaging Trackers (NITs) for the first direct measurement of target fragmentation caused by proton beams in cancer treatment. NITs are fine-grained nuclear emulsion films that offer a spatial resolution at the nanometric scale. DAMON’s pilot test exposed a NIT-based detector to 211 MeV protons, paving the way for the first study of target fragmentation in direct kinematics. In this paper the preliminary results regarding the multiplicity of the fragments and their track lengths are reported.

Robot-Assisted Ocular Tumour Radiotherapy Positioning and Tracking System.

Precise dose position distribution is crucial for ocular proton therapy. A non-invasive eye positioning and tracking system with novel structure is designed to reduce eye movement and facilitate precise dose by guiding the direction of patients' gaze. The system helps to achieve gaze guidance by controlling the light source fixed on two turntables above the patient's face. Tracking of the eye is achieved by cameras attached to the end of a 6DOFs robotic arm to capture the image reflected from a mirror above the patient's face. After all operation steps, the accuracy of the robotic arm is 0.18mm (SD 0.25mm) and the accuracy of the turntables is 0.01° (SD 0.02°). The EPTS is tested to be remotely controlled in real time with sufficient precision and repeatability. The system is expected to improve the safety and efficiency of ocular proton therapy.

420 - Initial experiences with immobilisation for proton therapy: Strategies and Challenges

420 - Initial experiences with immobilisation for proton therapy: Strategies and Challenges

Can input reconstruction be used to directly estimate uncertainty of a dose prediction U-Net model?

The reliable and efficient estimation of uncertainty in artificial intelligence (AI) models poses an ongoing challenge in many fields such as radiation therapy. AI models are intended to automate manual steps involved in the treatment planning workflow. We focus in this study on dose prediction models that predict an optimal dose trade-off for each new patient for a specific treatment modality. They can guide physicians in the optimization, be part of automatic treatment plan generation or support decision in treatmentindication. Most common uncertainty estimation methods are based on Bayesian approximations, like Monte Carlo dropout (MCDO) or Deep ensembling (DE). These two techniques, however, have a high inference time (i.e., require multiple inference passes) and might not work for detecting out-of-distribution (OOD) data (i.e., overlapping uncertainty estimate for in-distribution (ID) and OOD). In this study, we present a direct uncertainty estimation method and apply it for a dose prediction U-Net architecture. It can be used to flag OOD data and give information on the quality of the doseprediction. Our method consists in the addition of a branch decoding from the bottleneck which reconstructs the CT scan given as input. The input reconstruction error can be used as a surrogate of the model uncertainty. For the proof-of-concept, our method is applied to proton therapy dose prediction in head and neck cancer patients. A dataset of 60 oropharyngeal patients was used to train the network using a nested cross-validation approach with 11 folds (training: 50 patients, validation: 5 patients, test: 5 patients). For the OOD experiment, we used 10 extra patients with a different head and neck sub-location. Accuracy, time-gain, and OOD detection are analyzed for our method in this particular application and compared with the popular MCDO andDE. The additional branch did not reduce the accuracy of the dose prediction model. The median absolute error is close to zero for the target volumes and less than 1% of the dose prescription for organs at risk. Our input reconstruction method showed a higher Pearson correlation coefficient with the prediction error (0.620) than DE (0.447) and MCDO (between 0.599 and 0.612). Moreover, our method allows an easier identification of OOD (no overlap for ID and OOD data and a Z-score of 34.05). The uncertainty is estimated simultaneously to the regression task, therefore requires less time and computationalresources. This study shows that the error in the CT scan reconstruction can be used as a surrogate of the uncertainty of the model. The Pearson correlation coefficient with the dose prediction error is slightly higher than state-of-the-art techniques. OOD data can be more easily detected and the uncertainty metric is computed simultaneously to the regression task, therefore faster than MCDO or DE. The code and pretrained model are available on the gitlab repository: https://gitlab.com/ai4miro/ct-reconstruction-for-uncertainty-quatification-of-hdunet.

Intensity-modulated proton radiotherapy spares musculoskeletal structures in regional nodal irradiation for breast cancer: a dosimetric comparison.

Regional nodal irradiation (RNI) for breast cancer delivers radiation in proximity to the shoulder and torso, and radiation exposure may contribute to long-term upper extremity and postural morbidity. To date, no studies have assessed the differential dosimetric impact of proton versus photon radiation on shoulder and torso anatomy. This study examined clinically relevant musculoskeletal (MSK) structures and assessed the dose delivered with each modality. Ten MSK structures were contoured on IMPT (intensity-modulated proton therapy) and VMAT (volumetric modulated arc therapy) plans for 30 patients receiving RNI. Relevant dose metrics were compared for each of the structures. Intensity-modulated proton therapy dose was calculated using the relative biological effective value of 1.1. Hypo-fractionated plans were scaled to the equivalent dose in 2 Gy fractions (EQD2) using an alpha/beta ratio of four. Wilcoxon signed rank sum tests compared doses. Select three-dimensional and optimised VMAT plans were also informally compared. Each of the 10 structures received a statistically significantly lower dose with the use of IMPT compared with VMAT. Differences were greatest for posterior structures, including the trapezius, latissimus dorsi and glenohumeral joint. Mean absolute differences were as great as 23 Gy (supraspinatus D5cc) and up to 30-fold dose reductions were observed (deltoid D50cc). An average 3.7-fold relative dose reduction existed across all structures. Measures of low/intermediate dose (V15Gy and D50cc) showed the largest differences. Intensity-modulated proton therapy results in statistically lower radiation exposure to relevant shoulder and torso anatomy compared to photon radiation for patients requiring RNI. Prospective study is needed to correlate functional outcomes with radiation dose.

443 - Clinical evaluation of automated planning in photon backup plan generation for proton therapy: A pilot study

443 - Clinical evaluation of automated planning in photon backup plan generation for proton therapy: A pilot study

The Radiosurgery Society Working Groups on GRID, LATTICE, Microbeam, and FLASH Radiotherapies: 2022 to 2023 Advancements Symposium and Subsequent Progress Made

PurposeSince the inaugural workshop “Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy.” hosted by the NCI and sponsored by the Radiosurgery Society (RSS), growing collaborations and investigations have ensued among experts, practitioners, and researchers. The RSS GRID, Lattice, Microbeam & FLASH (GLMF) Working Groups were formed as a framework for these efforts and have focused on advancing the understanding of the biology, technical/physical parameters, trial design, and clinical practice of these new radiation therapy modalities. Methods and MaterialsIn view of the steadily increasing clinical interest in SFRT and FLASH, a full-day symposium entitled “Advancements in GRID, LATTICE, and FLASH Radiotherapy Symposium” was established in 2022 that immediately preceded the RSS scientific meeting. This well-attended symposium focused on clinical, technical, and physics approaches for SFRT, while closely examining relevant radiobiological underpinnings. Practical clinical trial development was a highlighted discussion. An additional section reviewed proton therapy and other particle-based techniques for the delivery of GRID and Lattice therapy. A treatment planning and delivery tutorial for GRID, Lattice, and proton GRID/Lattice was directed towards the real-world considerations for the development of new clinical GRID or LATTICE programs. An overall similar approach was applied to the discussion of FLASH. This report summarizes the content of the first GLMF Symposium and related work of the RSS GLMF Working Groups in the field of heterogeneous and ultra-high dose rate irradiation, over approximately 2 years. ResultsThe GLMF Working Groups have continued to expand in membership and attendance, and several resultant trial concepts, research efforts, academic discussions, and peer-reviewed publications have followed as the number of institutions and practitioners utilizing SFRT and FLASH continues to grow. ConclusionsThe GLFM Working Groups and the RSS continue to demonstrate excellent progress in proliferating use of and improving understanding of SFRT and ultra-high dose rate radiotherapy techniques.

Dosimetric and On-treatment Clinical Results of a Volumetric-based Skin-sparing Planning Technique for Patients Treated to the Breast and Chest Wall With Pencil-Beam Scanning Proton Therapy

PurposeThis study evaluates the hypothesis that a volumetric skin-sparing planning technique (SSPT) will reduce acute dermatitis in patients treated to the breast or chest wall (CW) with proton pencil beam scanning (PBS). MethodsIn January 2022, our center incorporated volumetric-based skin-sparing objectives in addition to skin hot-spot evaluation as a SSPT. The SSPT incorporated an objective to limit the volume of a skin evaluation structure (skin-eval) receiving 95% of the prescription dose or more (V95%Rx) to ideally <50%. We compared target coverage, robustness, skin-eval dosimetry, and acute on-treatment skin toxicity in patients treated with and without incorporation of this SSPT. Patients with skin/dermal lymphatic invasion or inflammatory breast cancer were excluded. Results84 patients who received breast/CW PBS were included (43 planned without and 41 with the SSPT). There was no difference in percentages of patients treated to the intact breast/CW/immediate CW reconstruction between groups. Mean skin-evalV95%Rx was 72% vs. 30%, p<0.0001, for those treated without versus with a SSPT. Maximum %Rx to the skin-eval volume of 0.03 cc, 0.3cc, and 1cc was higher in patients treated without versus with a SSPT (103.1% vs. 101.5%; 101.3% vs. 100.4%; and 101.8% vs. 99.7% (all p=<0.0001)), respectively. There was a small difference in the mean CTV V97.5%Rx in patients treated without versus with the SSPT (97.8% vs. 96.5%, p=0.0003). Patients planned utilizing the SSPT demonstrated reduced rates of Grade 1 breast pain at Week 2 (12% vs. 33%, p=0.0424) and Grade 2 and 3 dermatitis at Weeks 4 and 5 (Week 4 dermatitis ≥ grade 2, 18% vs. 43%, p=0.0224; Week 5 dermatitis ≥ grade 2, 45% vs. 69%, p=0.0006). There were numerically more patients requiring a treatment break or not completing the full intended prescription (4 vs. 1) in the pre-SSPT cohort. ConclusionsUse of a SSPT may reduce acute skin toxicity in breast cancer patients treated with PBS.

Proton dose calculation on cone-beam computed tomography using unsupervised 3D deep learning networks

Background and PurposePoor image quality of cone-beam computed tomography (CBCT) images can hinder proton dose calculation to assess the influence of anatomy changes. The aim of this study was to evaluate image quality and proton dose calculation accuracy of synthetic CTs generated from CBCT using unsupervised 3D deep-learning networks. Materials and methodsA total of 102 head-and-neck cancer patients were used to train (N=82) and test (N=20) i) a cycle-consistent generative adversarial network, ii) a contrastive unpaired translation, and iii) a fusion of the two (CycleCUT). For patients in the test set, a repeat CT was deformably registered to a same-day CBCT to create a ground-truth CT for comparison. The proton plan was re-calculated on the ground-truth CT and synthetic CTs. The image quality of the synthetic CTs was evaluated using peak signal-to-noise ratio, structural similarity index measure, mean error, and mean absolute error (MAE). Proton dose calculation accuracy was assessed through 3D gamma analysis and dose-volume-histogram parameters. ResultsAll synthetic CTs accurately preserved the CBCT anatomy (verified by visual inspection) while improving the image quality. The CycleCUT network had slightly improved image quality compared to the other networks (MAE in body: 53 Hounsfield units (HU) vs. 54/55 HU). All networks had similar proton dose calculation accuracy with gamma passing rate above 97%. ConclusionsAll three evaluated networks generated synthetic CT images with dose distributions comparable to those of conventional fan-beam CT. The synthetic CT generation was fast, making all networks feasible for adaptive proton therapy.

Stochastic model for predicting the temporal structure of the plan delivery in a synchrotron-based pencil beam scanning proton therapy system

Accurately predicting dose delivery is crucial for achieving fully personalized treatments in external beam radiation therapy. However, this task remains challenging in some current technologies. In the case of Proton Therapy, for example, current systems employ complex strategies where a pencil beam is scanned in the tumor for treatment delivery. Some parameters in these treatments fluctuate and cannot be fully controlled. Therefore, a stochastic model that accounts for temporal uncertainties can be the best approach to describe these behaviors, particularly when the time-dependent beam interacts with other processes such as moving tumors or organs at risk.This paper aims to provide medical physicists with a tool for accurately predicting the temporal structure of beam delivery. To achieve this, we followed a two-step process. First, we characterized the probability distributions for all relevant times in dose delivery. Second, we developed a model based on the measured data. This model serves as a starting point to improve treatment planning performance by providing a range of expected times for dose delivery. While the process was carried out using a compact synchrotron at our university, it can be easily adapted to other technologies.

A new approach to assessing the consequences of radiation on the eye

The authors propose a new approach to assessing the consequences of exposure to ionizing radiation on the structures of the eye. The approach is based on the results recently obtained by the authors together with employees of the Joint Institute for Nuclear Research in Dubna, according to which radiation exposure causes oxidation of the bisretinoids contained in the structures of the eye - the retina and retinal pigment epithelium. As a result of this oxidation, the fluorescence spectrum of bisretinoids shifts to the blue region of the visible spectrum. The shift in the fluorescence spectrum can be recorded non-invasively using the method of recording fundus autofluorescence, which is currently generally accepted in ophthalmology. Since the oxidation of bisretinoids occurs during radiation exposure, it becomes possible almost immediately after irradiation to assess the degree of impact of ionizing radiation on both the structures of the eye and the body as a whole. There is no analogue to such a non-invasive assessment of the effects of radiation on the body. The proposed approach may become important for assessing the radiation safety of nuclear industry workers, astronauts, and patients undergoing proton or gamma therapy.

RayStation/GATE Monte Carlo simulation framework for verification of proton therapy based on the 12N imaging

Objective.12N, having a half-life of 11 ms, is a highly effective positron emitter that can potentially provide near real-time feedback in proton therapy. There is currently no framework for comparing and validating positron emission imaging of12N. This work describes the development and validation of a Monte Carlo (MC) framework to calculate the images of12N, as well as long-lived isotopes, originating from activation by protons.Approach. The available dual-panel Biograph mCT PET scanner was modeled in GATE and validated by comparing the simulated sensitivity map with the measured one. The distributions of12N and long-lived isotopes were calculated by RayStation and used as the input of GATE simulations. The RayStation/GATE combination was verified using proton beam irradiations of homogeneous phantoms. A 120 MeV pulsed pencil beam with 108protons per pulse was used. Two-dimensional images were created from the GATE output and compared with the images based on the measurements and the 1D longitudinal projection of the full 2D image was used to calculate the12N activity range.Main results. The simulated sensitivity in the center of the FoV (5.44%) agrees well with the measured one (5.41%). The simulated and measured 2D sensitivity maps agree in good detail. The relative difference between the measured and simulated positron activity range for both12N and long-lived isotopes is less than 1%. The broadening of the12N images relative to those of the longer-lived isotopes can be understood in terms of the large positron range of12N.Significance. We developed and validated a MC framework based on RayStation/GATE to support the in-beam PET method for quality assurance of proton therapy. The inclusion of the very short-lived isotope12N makes the framework useful for developing near real-time verification. This represents a significant step towards translating12N real-time in vivo verification to the clinic.