Range Uncertainty In Proton Therapy Research Articles

Benefit of range uncertainty reduction in robust optimisation for proton therapy of brain, head-and-neck and breast cancer patients

Background and PurposeThe primary cause of range uncertainty in proton therapy is inaccuracy in estimating the stopping-power ratio from computed tomography. This study examined the impact on dose-volume metrics by reducing range uncertainty in robust optimisation for a diverse patient cohort and determined the level of range uncertainty that resulted in a relevant reduction in doses to organs-at-risk (OARs). Materials and MethodsThe effect of reducing range uncertainty on OAR doses was evaluated by robustly optimising six proton plans with varying range uncertainty levels (ranging from 3.5% in the original plan to 1.0%), keeping setup uncertainty fixed. All plans used the initial clinical treatment plan’s beam directions and optimisation objectives and were optimised until a clinically acceptable plan was achieved across all setup and range scenarios. The effect of reduced range uncertainty on dose-volume metrics for OARs near the target was evaluated. This study included 30 brain cancer patients, as well as five head-and-neck and five breast cancer patients, investigating the relevance of reducing range uncertainty when different setup uncertainties were used. ResultsLowering range uncertainty slightly reduced the nominal dose to surrounding tissue. For body volume receiving 80% of the prescribed dose, reducing range uncertainty from 3.5% to 2.0% resulted in a median decrease of 4 cm3 for the brain, 17 cm3 for head-and-neck, and 27 cm3 for breast cancer patients. ConclusionsReducing range uncertainty in robust optimisation showed a reduction in dose to OARs. The clinical relevance depends on the affected organs and the clinical dose constraints.

Impact of and interplay between proton arc therapy and range uncertainties in proton therapy for head-and-neck cancer

Objective. Proton therapy reduces the integral dose to the patient compared to conventional photon treatments. However, in vivo proton range uncertainties remain a considerable hurdle. Range uncertainty reduction benefits depend on clinical practices. During intensity-modulated proton therapy (IMPT), the target is irradiated from only a few directions, but proton arc therapy (PAT), for which the target is irradiated from dozens of angles, may see clinical implementation by the time considerable range uncertainty reductions are achieved. It is therefore crucial to determine the impact of PAT on range uncertainty reduction benefits. Approach. For twenty head-and-neck cancer patients, four different treatment plans were created: an IMPT and a PAT treatment plan assuming current clinical range uncertainties of 3.5% (IMPT3.5% and PAT3.5%), and an IMPT and a PAT treatment plan assuming that range uncertainties can be reduced to 1% (IMPT1% and PAT1%). Plans were evaluated with respect to target coverage and organ-at-risk doses as well as normal tissue complication probabilities (NTCPs) for parotid glands (endpoint: parotid gland flow <25%) and larynx (endpoint: larynx edema). Main results. Implementation of PAT (IMPT3.5%−PAT3.5%) reduced mean NTCPs in the nominal and worst-case scenario by 3.2 percentage points (pp) and 4.2 pp, respectively. Reducing range uncertainties from 3.5% to 1% during use of IMPT (IMPT3.5%−IMPT1%) reduced evaluated NTCPs by 0.9 pp and 2.0 pp. Benefits of range uncertainty reductions subsequently to PAT implementation (PAT3.5%−PAT1%) were 0.2 pp and 1.0 pp, with considerably higher benefits in bilateral compared to unilateral cases. Significance. The mean clinical benefit of implementing PAT was more than twice as high as the benefit of a 3.5%–1% range uncertainty reduction. Range uncertainty reductions are expected to remain beneficial even after PAT implementation, especially in cases with target positions allowing for full leveraging of the higher number of gantry angles during PAT.

Improved sub-milimeter range-verification method for proton therapy using a composite hadron tumour marker (HTM)

Objective. The results of a follow-up experiment investigating a novel method for sub-milimetre range verification (RV) in proton therapy (PT) are presented. Approach. The method consists of implanting a hadron tumour marker (HTM) near the planned treatment volume, and measuring the γ-ray signals emitted as a result of activation by the proton beam. These signals are highly correlated with the energy of the beam impinging on the HTM and can provide an absolute measurement of the range of the beam relative to the position of the HTM, which is independent of any uncertainties in beam delivery. Main results. Three candidate HTM materials were identified and combined into a single composite HTM, which makes use of the strongest reaction in each material. The setup of the previous experiment was improved on by using high-purity germanium detectors to measure the γ-ray signal with a higher resolution than was previously achieved. A PMMA phantom was also used to simulate the γ-ray background from tissue activation. HTM RV using the data collected in this study yielded range measurements whose average deviation from the expected value was 0.13(22)mm. Significance. Range uncertainty in PT limits the prescribed treatment plan for cancer patients with large safety margins and constrains the direction of the proton beam in relation to any organ at risk. The sub-milimetre range uncertainty achieved in this study using HTM RV, if implemented clinically, would allow for a reduction in the size of safety margins, increasing the therapeutic window for PT.

Validation of an MR-based multimodal method for molecular composition and proton stopping power ratio determination using ex vivo animal tissues and tissue-mimicking phantoms

Objective. Range uncertainty in proton therapy is an important factor limiting clinical effectiveness. Magnetic resonance imaging (MRI) can measure voxel-wise molecular composition and, when combined with kilovoltage CT (kVCT), accurately determine mean ionization potential (I m ), electron density, and stopping power ratio (SPR). We aimed to develop a novel MR-based multimodal method to accurately determine SPR and molecular compositions. This method was evaluated in tissue-mimicking and ex vivo porcine phantoms, and in a brain radiotherapy patient. Approach. Four tissue-mimicking phantoms with known compositions, two porcine tissue phantoms, and a brain cancer patient were imaged with kVCT and MRI. Three imaging-based values were determined: SPRCM (CT-based Multimodal), SPRMM (MR-based Multimodal), and SPRstoich (stoichiometric calibration). MRI was used to determine two tissue-specific quantities of the Bethe Bloch equation (I m , electron density) to compute SPRCM and SPRMM. Imaging-based SPRs were compared to measurements for phantoms in a proton beam using a multilayer ionization chamber (SPRMLIC). Main results. Root mean square errors relative to SPRMLIC were 0.0104(0.86%), 0.0046(0.45%), and 0.0142(1.31%) for SPRCM, SPRMM, and SPRstoich, respectively. The largest errors were in bony phantoms, while soft tissue and porcine tissue phantoms had <1% errors across all SPR values. Relative to known physical molecular compositions, imaging-determined compositions differed by approximately ≤10%. In the brain case, the largest differences between SPRstoich and SPRMM were in bone and high lipids/fat tissue. The magnitudes and trends of these differences matched phantom results. Significance. Our MR-based multimodal method determined molecular compositions and SPR in various tissue-mimicking phantoms with high accuracy, as confirmed with proton beam measurements. This method also revealed significant SPR differences compared to stoichiometric kVCT-only calculation in a clinical case, with the largest differences in bone. These findings support that including MRI in proton therapy treatment planning can improve the accuracy of calculated SPR values and reduce range uncertainties.

Tackling range uncertainty in proton therapy: Development and evaluation of a new multi-slit prompt-gamma camera (MSPGC) system

In theory, the sharp dose falloff at the distal end of a proton beam allows for high conformal dose to the target. However, conformity has not been fully achieved in practice, primarily due to beam range uncertainty, which is approximately 4% and varies slightly across institutions. To address this issue, we developed a new range verification system prototype: a multi-slit prompt-gamma camera (MSPGC). This system features high prompt-gamma detection sensitivity, an advanced range estimation algorithm, and a precise camera positioning system. We evaluated the range measurement precision of the prototype for single spot beams with varying energies, proton quantities, and positions, as well as for spot-scanning proton beams in a simulated SSPT treatment using a phantom. Our results demonstrated high accuracy (<0.4 mm) in range measurement for the tested beam energies and positions. Measurement precision increased significantly with the number of protons, achieving 1% precision with 5 × 108 protons. For spot-scanning proton beams, the prototype ensured more than 5 × 108 protons per spot with a 7 mm or larger spot aggregation, achieving 1% range measurement precision. Based on these findings, we anticipate that the clinical application of the new prototype will reduce range uncertainty (currently approximately 4%) to 1% or less.

In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO.

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam’s Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.

Radiation shielding assessment of high‐energy proton imaging at a proton therapy facility

BackgroundProton imaging makes use of high‐energy, low‐intensity proton beams that fully traverse the patient and has been suggested to reduce range uncertainty in proton therapy. Upright patient positioning with proton imaging is being considered for a fixed beam room of a new proton therapy facility currently under construction. Considering that the yield and energy spectrum of secondary radiation from high‐energy proton beams is proton beam energy dependent, an assessment of radiation shielding at the energies required for proton imaging should be performed prior to use. Furthermore, NCRP 144 recommends that pion production be considered for proton energies greater than 300 MeV, which are not typically utilized for proton therapy but may be required for proton imaging.PurposeThe purpose of this work was to determine whether proton treatment and imaging with an upright patient positioning system on a fixed beamline were acceptable from a radiation shielding perspective. This is the first report on radiation shielding assessment of proton imaging applications and includes consideration of pion production at the proton beam energy of 330 MeV.MethodsThe Geant4 Monte Carlo toolkit was used for the radiation shielding assessment. The calculations consisted of the generation of secondary particle phase‐space files by simulating the passage of high‐energy proton beams in two target materials, and subsequent simulation of the secondary particles in the proton therapy facility geometry. Particle fluence was converted to operational and protection radiation safety quantities with a custom python script for assessment of instantaneous and annual doses, respectively.ResultsThe total yields of pions from a 330‐MeV proton beam were many orders of magnitude less than that of neutrons and photons. Three‐dimensional maps of ambient dose rate for a 330‐MeV proton beam showed doses arising from secondary neutrons and photons far exceed those arising from pion production. Incorporating representative annual workloads into the calculation demonstrated that proton imaging doses outside the shielded area were negligible compared to those arising from proton therapy.ConclusionsPion production has a negligible impact on the radiation shielding of proton imaging at 330 MeV relative to neutron and photon production. Radiation shielding designed for proton therapy is adequate for high‐energy proton imaging applications.

NTCP Modeling of Late Effects for Head and Neck Cancer: A Systematic Review.

NTCP Modeling of Late Effects for Head and Neck Cancer: A Systematic Review.

OC-0705: Dose restoration: an online adaptive strategy to fight against range uncertainties in proton therapy

OC-0705: Dose restoration: an online adaptive strategy to fight against range uncertainties in proton therapy

Sparse deconvolution of proton radiography data to estimate water equivalent thickness maps.

In proton therapy, the conversion of the planning computed tomography (CT) into proton stopping powers is tainted by uncertainties which may jeopardize dose conformity. Proton radiography provides a direct information on the energy reduction of protons in the patient. However, it is currently limited by the degradation ("blurring") of the one-dimensional depth-dose deposition profiles which constitute the pixels. An iterative algorithm is implemented to extract high-resolution water equivalent thickness (WET) maps from the measurements of depth-dose profiles acquired with a multilayer ionization chamber. The method relies on the assumption that those curves are a function of the WET, which can benefit from a sparse representation. When used without relying on any prior knowledge derived from the planning CT, the method already outperforms the published one in terms of accuracy. We also propose a variant which integrates the planning CT in a robust fashion to further improve the deconvolution result and reach an accuracy of 1.5mm on the estimated WET. The methods are applied to both synthetic data and actual proton radiography acquisitions on phantoms. Besides the increase in accuracy achieved in the estimation of WET maps from proton radiography data, we demonstrate that the proposed deconvolution algorithm is also more robust with respect to confounding factors such as residual setup errors or changes in the anatomy. Therefore, proton radiography using a range probe provides both the required accuracy to assess and reduce range uncertainty in proton therapy and the simplicity of integrated-mode proton radiography.

Effects of the Bragg peak degradation due to lung tissue in proton therapy of lung cancer patients

PurposeTo quantify the effects of the Bragg peak degradation due to lung tissue on treatment plans of lung cancer patients with spot scanning proton therapy and to give a conservative approximation of these effects.Methods and materialsTreatment plans of five lung cancer patients (tumors of sizes 2.7–46.4 cm3 at different depths in the lung) were optimized without consideration of the Bragg peak degradation. These treatment plans were recalculated with the Monte Carlo code TOPAS in two scenarios: in a first scenario, the treatment plans were calculated without including the Bragg peak degradation to reproduce the dose distribution predicted by the treatment-planning system (TPS). In a second scenario, the treatment plans were calculated while including the Bragg peak degradation. Subsequently, the plans were compared by means of Dmean, D98% and D2% in the clinical target volume (CTV) and organs at risk (OAR). Furthermore, isodose lines were investigated and a gamma index analysis was performed.ResultsThe Bragg peak degradation leads to a lower dose in the CTV and higher doses in OARs distal to the CTV compared to the prediction from the TPS. The reduction of the mean dose in the CTV was − 5% at maximum and − 2% on average. The deeper a tumor was located in the lung and the smaller its volume the bigger was the effect on the CTV. The enhancement of the mean dose in OARs distal to the CTV was negligible for the cases investigated.ConclusionsEffects of the Bragg peak degradation due to lung tissue were investigated for lung cancer treatment plans in proton therapy. This study confirms that these effects are clinically tolerable to a certain degree in the current clinical context considering the various more critical dose uncertainties due to motion and range uncertainties in proton therapy.

Protonthérapie des carcinomes épidermoïdes des voies aérodigestives supérieures : de la physique à la clinique

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.

SP-0471 Treatment Planning and Verification with Proton CT and Proton Radiography to Reduce Range Uncertainties in Proton Therapy

SP-0471 Treatment Planning and Verification with Proton CT and Proton Radiography to Reduce Range Uncertainties in Proton Therapy

Clinical Feasibility of Single-Source Dual-spiral 4D Dual-Energy CT for Proton Treatment Planning Within the Thoracic Region

Single-source dual-spiral dual-energy computed tomography (DECT) provides additional patient information but is prone to motion between the 2 consecutively acquired computed tomography (CT) scans. Here, the clinical applicability of dual-spiral time-resolved DECT (4D-DECT) for proton treatment planning within the thoracic region was evaluated. Dual-spiral 4D-DECT scans of 3 patients with lung cancer were acquired. For time-averaged datasets and 4 breathing phases, the geometric conformity of 80 kVp and 140 kVp 4D-DECT scans before image post-processing was assessed by normalized cross correlation (NCC). Additionally, the conformity of the corresponding DECT-derived 58keV and 79keV pseudo-monoenergetic CT datasets after image post-processing, including deformable image registration (DIR), was determined. To analyze the reliability of proton dose calculation, clinical (PlanClin) and artificial worst-case (PlanWorstCase, targeting the diaphragm) treatment plans were calculated on 140 kVp and 79keV datasets and compared with gamma analyses (0.1% dose-difference and 1mm distance-to-agreement criterion). The applicability of a patient-specific DECT-based prediction of stopping-power ratio (SPR) was investigated and proton range shifts compared with the clinical heuristic CT-number-to-SPR conversion were assessed. Finally, the delineation variability of an experienced radiation oncologist was quantified. Dual-spiral 4D-DECT scans without DIR showed a high geometric conformity, with an average NCC ± standard deviation of 98.7%±1.0% when including all patient voxels or 88.2%±7.8% when considering only lung. DIR improved the conformity, leading to an average NCC of 99.9%±0.1% and 99.6%±0.5%, respectively. PlanClin dose distributions on 140 kVp and 79keV datasets were similar, with an average gamma passing rate of 99.9% (99.2%-100%). The worst-case evaluation still revealed high passing rates (99.3% on average, 92.4% as minimum). Clinically relevant mean range shifts of 2.2%±1.2% were determined between patient-specific DECT-based SPR prediction and clinical heuristic CT-number-to-SPR conversion. The intra-observer delineation variability was slightly reduced using additional DECT-derived datasets. The 79keV pseudo-monoenergetic CT datasets can be consistently obtained from dual-spiral 4D-DECT and are applicable for dose calculation. Patient-specific DECT-based SPR prediction performed well and potentially reduces range uncertainty in proton therapy of patients with lung cancer.

Abstract ID: 138 Fluence modulated proton computed tomography

Proton computed tomography (pCT) has recently seen considerable research interest as a means of reducing range uncertainties in proton therapy, by reconstructing directly relative stopping power to water (RSP). Recent detector developments have permitted the development of two list-mode pCT scanner prototypes based on broad (passively scattered) proton beam delivery [1] , [2] . In this Monte Carlo (MC) simulation study, the application of fluence field modulated computed tomography (FFMCT), initially developed for X-ray CT [3] , to pCT is presented. Fluence modulated pCT (FMpCT) scans can be acquired by utilizing pencil beam (PB) scanning and can achieve variable image quality in a pCT image. Dose calculation accuracy may thus be simultaneously preserved in the beam path in parallel with imaging dose reduction. Using MC simulations of an ideal list-mode pCT scanner, a uniform cylinder and two patients were studied. Regions of interests (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy and noise of the reconstructed RSP. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Furthermore, the concept of FMpCT was tested on experimental data by creating pseudo FMpCT scans from broad beam scans acquired with a pCT prototype. For the virtual phantoms, FMpCT noise in ROIs at 1% of FF was equivalent to that of FF images. Integral imaging dose reduction up to 56% was achieved for the two patients for that modulation. Corresponding proton dose calculations on FMpCT images agreed to those from reference images. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI.

Can Robust Optimization for Range Uncertainty in Proton Therapy Act as a Surrogate for Biological Optimization?

To investigate how robust optimization (to address range uncertainties) affects the dose and linear energy transfer (LET) distribution in the target and organs at risk (OARs) compared to LET-based inverse optimization (to address relative biological effectiveness - RBE - effects) in intensity modulated proton therapy (IMPT). A GPU-based Monte Carlo code was used to calculate both physical dose and dose-averaged LET for all pencil beams for IMPT proton plans for previously treated ependymoma patients. The plans were initially optimized based on physical dose constraints. A previously developed LET-based optimization algorithm, using a prioritized optimization scheme, was then applied to modify the LET distribution while constraining the physical dose objectives within 3% of the initial plan. The objective functions for this step were based on the product of LET and physical dose (LETxD) as an approximation of the additional biological dose that is caused by high LET. For the robust optimization all pencil beam dose and dose-averaged LET calculations were repeated for patient CT image sets with modified HU values, resulting in uniform ±2.33% and ±4.77% range deviations, for a total of five different scenarios. The level of range deviation and probability of these scenarios was estimated assuming a Gaussian-shaped probability of range uncertainty, with 1.5 sigma value of 3.5%, which is the clinically used range uncertainty in our institution. The dose and LETxD distributions resulting from the initial, LET-based and robust optimizations were then compared in terms of target coverage and OAR sparing. Our results show that both LET-based and robust optimization techniques of IMPT plans resulted in significantly reduced maximum LETxD values in the OARs adjacent to the target compared to the initial plan. Robust optimization avoids dose gradients in beam direction in the dose contributions of individual beams, effectively resembling single field uniformly optimized plans. For an ependymoma patient (Table 1) this results in higher median LETxD values for both the target and brainstem, compared to the initial plan. LET-based optimization most effectively reduced the median and mean LETxD to the brainstem, however also resulted in somewhat smaller median LETxD value for the target. Both inverse LET-based and robust optimization techniques can be a realistic approach to manage biological dose hot spots in the OARs adjacent to the target. Depending on the clinical dosimetric priorities set for each patient case, each one can offer distinct benefits towards avoiding potentially increased risk of side effects from elevated RBE of proton beams near the end of range.Abstract 230; Table 1Initial planLET-reoptimized planRobustly optimized planTargetD98 (Gy)484848.2D50 (Gy)50.750.650.9Median LETxD4.64.25.5BrainstemD50 (Gy)49.749.449.5Median LETxD4.83.85.7Max LETxD (2%)9.86.78.5 Open table in a new tab

Pre-treatment patient-specific stopping power by combining list-mode proton radiography and x-ray CT

The relative stopping power (RSP) uncertainty is the largest contributor to the range uncertainty in proton therapy. The purpose of this work was to develop a systematic method that yields accurate and patient-specific RSPs by combining (1) pre-treatment x-ray CT and (2) daily proton radiography of the patient. The method was formulated as a penalized least squares optimization problem (argmin()). The parameter A represents the cumulative path-length crossed by the proton in each material, separated by thresholding on the HU. The material RSPs (water equivalent thickness/physical thickness) are denoted by x. The parameter b is the list-mode proton radiography produced using Geant4 simulations. The problem was solved using a non-negative linear-solver with . A was computed by superposing proton trajectories calculated with a cubic or linear spline approach to the CT. The material’s RSP assigned in Geant4 were used for reference while the clinical HU-RSP calibration curve was used for comparison. The Gammex RMI-467 phantom was first investigated. The standard deviation between the estimated material RSP and the calculated RSP is 0.45%. The robustness of the techniques was then assessed as a function of the number of projections and initial proton energy. Optimization with two initial projections yields precise RSP (⩽1.0%) for 330 MeV protons. 250 MeV protons have shown higher uncertainty (⩽2.0%) due to the loss of precision in the path estimate. Anthropomorphic phantoms of the head, pelvis, and lung were subsequently evaluated. Accurate RSP has been obtained for the head (), the lung () and the pelvis (). The range precision has been optimized using the calibration curves obtained with the algorithm, yielding a mean difference to the reference of 0.11 ±0.09%, 0.28 ± 0.34% and in the same order. The solution’s accuracy is limited by the assumed HU/RSP bijection, neglecting inherent degeneracy. The proposed formulation of the problem with prior knowledge x-ray CT demonstrates potential to increase the accuracy of present RSP estimates.

An end-to-end assessment of range uncertainty in proton therapy using animal tissues

Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues.Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences.The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively.Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams’ superior dose advantage over conventional photon-based radiation therapy.

Sci‐Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques ‐ 01: On the use of proton radiography to reduce beam range uncertainties and improve patient positioning accuracy in proton therapy

To present two related developments of proton radiography (pRad) to minimize range uncertainty in proton therapy. The first combines a pRad with an X‐ray CT to produce a patient‐specific relative stopping power (RSP) map. The second aims to improve the pRad spatial resolution for accurate registration prior to the first. The enhanced‐pRad can also be used in a novel proton‐CT reconstruction algorithm.Monte Carlo pRad were computed from three phantoms; the Gammex, the Catphan and an anthropomorphic head. An optimized cubic‐spline estimator derives the most likely path. The length crossed by the protons voxel‐by‐voxel was calculated by combining their estimated paths with the CT. The difference between the theoretical (length×RSP) and measured energy loss was minimized through a least squares optimization (LSO) algorithm yielding the RSP map. To increase pRad spatial resolution for registration with the CT, the phantom was discretized into voxels columns. The average column RSP was optimized to maximize the proton energy loss likelihood (MLE).Simulations showed precise RSP (&lt;0.75%) for Gammex materials except low‐density lung (&lt;1.2%). For the head, accurate RSP were obtained (µ=−0.10%1.5σ=1.12%) and the range precision was improved (ΔR80 of −0.20±0.35%). Spatial resolution was increased in pRad (2.75 to 6.71 lp/cm) and pCT from MLE‐enhanced pRad (2.83 to 5.86 lp/cm).The LSO decreases the range uncertainty (R80σ&lt;1.0%) while the MLE‐enhanced pRad spatial resolution (+244%) and is a great candidate for pCT reconstruction.

SU‐G‐TeP2‐13: Patient‐Specific Reduction of Range Uncertainties in Proton Therapy by Proton Radiography with a Multi‐Layer Ionization Chamber

Purpose:The conversion from Hounsfield units (HU) to stopping powers is a major source of range uncertainty in proton therapy (PT). Our contribution shows how proton radiographs (PR) acquired with a multi‐layer ionization chamber in a PT center can be used for accurate patient positioning and subsequently for patient‐specific optimization of the conversion from HU to stopping powers.Methods:A multi‐layer ionization chamber was used to measure the integral depth‐dose (IDD) of 220 MeV pencil beam spots passing through several anthropomorphic phantoms. The whole area of interest was imaged by repositioning the couch and by acquiring a 45×45 mm2 frame for each position. A rigid registration algorithm was implemented to correct the positioning error between the proton radiographs and the planning CT. After registration, the stopping power map obtained from the planning CT with the calibration curve of the treatment planning system was used together with the water equivalent thickness gained from two proton radiographs to generate a phantom‐specific stopping power map.Results:Our results show that it is possible to make a registration with submillimeter accuracy from proton radiography obtained by sending beamlets separated by more than 1 mm. This was made possible by the complex shape of the IDD due to the presence of lateral heterogeneities along the path of the beam. Submillimeter positioning was still possible with a 5 mm spot spacing. Phantom specific stopping power maps obtained by minimizing the range error were cross‐verified by the acquisition of an additional proton radiography where the phantom was positioned in a random but known manner.Conclusion:Our results indicate that a CT‐PR registration algorithm together with range‐error based optimization can be used to produce a patient‐specific stopping power map.Sylvain Deffet reports financial funding of its PhD thesis by Ion Beam Applications (IBA) during the confines of the study and outside the submitted work.Francois Vander Stappen reports being employed by Ion Beam Applications (IBA) during the confines of the study and outside the submitted work.