The integration of magnetic resonance imaging (MRI) and proton therapy for on-line image-guidance is expected to reduce dose delivery uncertainties during treatment. Yet, the proton beam experiences ...a Lorentz force induced deflection inside the magnetic field of the MRI scanner, and several methods have been proposed to quantify this effect. We analyze their structural differences and compare results of both analytical and Monte Carlo models. We find that existing analytical models are limited in accuracy and applicability due to critical approximations, especially including the assumption of a uniform magnetic field. As Monte Carlo simulations are too time-consuming for routine treatment planning and on-line plan adaption, we introduce a new method to quantify and correct for the beam deflection, which is optimized regarding accuracy, versatility and speed. We use it to predict the trajectory of a mono-energetic proton beam of energy E0 traversing a water phantom behind an air gap within an omnipresent uniform transverse magnetic flux density B0. The magnetic field induced dislocation of the Bragg peak is calculated as function of E0 and B0 and compared to results obtained with existing analytical and Monte Carlo methods. The deviation from the Bragg peak position predicted by Monte Carlo simulations is smaller for the new model than for the analytical models by up to 2 cm. The model is faster than Monte Carlo methods, less assumptive than the analytical models and applicable to realistic magnetic fields. To compensate for the predicted Bragg peak dislocation, a numerical optimization strategy is introduced and evaluated. It includes an adjustment of both the proton beam entrance angle and energy of up to 25° and 5 MeV, depending on E0 and B0. This strategy is shown to effectively reposition the Bragg peak to its intended location in the presence of a magnetic field.
Purpose
Given its sensitivity to anatomical variations, proton therapy is expected to benefit greatly from integration with magnetic resonance imaging for online anatomy monitoring during ...irradiation. Such an integration raises several challenges, as both systems mutually interact. The proton beam will experience quasi‐continuous energy loss and energy‐dependent electromagnetic deflection at the same time, giving rise to a deflected beam trajectory and an altered dose distribution with a displaced Bragg peak. So far, these effects have only been predicted using Monte Carlo and analytical models, but no clear consensus has been reached and experimental benchmark data are lacking. We measured proton beam trajectories and Bragg peak displacement in a homogeneous phantom placed inside a magnetic field and compared them to simulations.
Methods
Planar dose distributions of proton pencil beams (80–180 MeV) traversing the field of a 0.95 T NdFeB permanent magnet while depositing energy in a PMMA slab phantom were measured using EBT3 radiochromic films and simulated using the Geant4 toolkit. Deflected beam trajectories and the Bragg peak displacement were extracted from the measured planar dose distributions and compared against the simulations.
Results
The lateral beam deflection was clearly visible on the EBT3 films and ranged from 1 to 10 mm for 80 to 180 MeV, respectively. Simulated and measured beam trajectories and Bragg peak displacement agreed within 0.8 mm for all studied proton energies.
Conclusions
These results prove that the magnetic field‐induced Bragg peak displacement is both measurable and accurately predictable in a homogeneous phantom at 0.95 T, and allows Monte Carlo simulations to be used as gold standard for proton beam trajectory prediction in similar frameworks for MR‐integrated proton therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Background MR‐integrated proton therapy is under development. It consists of the unique challenge of integrating a proton pencil beam scanning (PBS) beam line nozzle with an magnetic ...resonance imaging (MRI) scanner. The magnetic interaction between these two components is deemed high risk as the MR images can be degraded if there is cross‐talk during beam delivery and image acquisition. Purpose To create and benchmark a self‐consistent proton PBS nozzle model for empowering the next stages of MR‐integrated proton therapy development, namely exploring and de‐risking complete integrated prototype system designs including magnetic shielding of the PBS nozzle. Materials and Methods Magnetic field (COMSOL ) and radiation transport (Geant4) models of a proton PBS nozzle located at OncoRay (Dresden, Germany) were developed according to the manufacturers specifications. Geant4 simulations of the PBS process were performed by using magnetic field data generated by the COMSOL simulations. In total 315 spots were simulated which consisted of a scan pattern with 5 cm spot spacings and for proton energies of 70, 100, 150, 200, and 220 MeV. Analysis of the simulated deflection at the beam isocenter plane was performed to determine the self‐consistency of the model. The magnetic fringe field from a sub selection of 24 of the 315 spot simulations were directly compared with high precision magnetometer measurements. These focused on the maximum scanning setting of 20 cm beam deflection as generated from the second scanning magnet in the PBS for a proton beam energy of 220 MeV. Locations along the beam line central axis (CAX) were measured at beam isocenter and downstream of 22, 47, 72, 97, and 122 cm. Horizontal off‐axis positions were measured at 22 cm downstream of isocenter ( 50, 100, and 150 cm from CAX). Results The proton PBS simulations had good spatial agreement to the theoretical values in all 315 spots examined at the beam line isocenter plane (0–2.9 mm differences or within 1.5 % of the local spot deflection amount). Careful analysis of the experimental measurements were able to isolate the changes in magnetic fields due solely to the scanning magnet contribution, and showed 1.9 1.2 –9.4 1.2 changes over the range of measurement locations. Direct comparison with the equivalent simulations matched within the measurement apparatus and setup uncertainty in all but one measurement point. Conclusions For the first time a robust, accurate and self‐consistent model of a proton PBS nozzle assembly has been created and successfully benchmarked for the purposes of advancing MR‐integrated proton therapy research. The model will enable confidence in further simulation based work on fully integrated designs including MRI scanners and PBS nozzle magnetic shielding in order to de‐risk and realize the full potential of MR‐integrated proton therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Introduction
In large brain metastases (BM) with a diameter of more than 2 cm there is an increased risk of radionecrosis (RN) with standard stereotactic radiosurgery (SRS) dose prescription, while ...the normal tissue constraint is exceeded. The tumor control probability (TCP) with a single dose of 15 Gy is only 42%. This
in silico
study tests the hypothesis that isotoxic dose prescription (IDP) can increase the therapeutic ratio (TCP/Risk of RN) of SRS in large BM.
Materials and methods
A treatment-planning study with 8 perfectly spherical and 46 clinically realistic gross tumor volumes (GTV) was conducted. The effects of GTV size (0.5–4 cm diameter), set-up margins (0, 1, and 2 mm), and beam arrangements (coplanar vs non-coplanar) on the predicted TCP using IDP were assessed. For single-, three-, and five-fraction IDP dose–volume constraints of V
12Gy
= 10 cm
3
, V
19.2
Gy
= 10 cm
3
, and a V
20Gy
= 20 cm
3
, respectively, were used to maintain a low risk of radionecrosis.
Results
In BM of 4 cm in diameter, the maximum achievable single-fraction IDP dose was 14 Gy compared to 15 Gy for standard SRS dose prescription, with respective TCPs of 32 and 42%. Fractionated SRS with IDP was needed to improve the TCP. For three- and five-fraction IDP, a maximum predicted TCP of 55 and 68% was achieved respectively (non-coplanar beams and a 1 mm GTV-PTV margin).
Conclusions
Using three-fraction or five-fraction IDP the predicted TCP can be increased safely to 55 and 68%, respectively, in large BM with a diameter of 4 cm with a low risk of RN. Using IDP, the therapeutic ratio of SRS in large BM can be increased compared to current SRS dose prescription.
On-line image guidance using magnetic resonance (MR) imaging is expected to improve the targeting accuracy of proton therapy. However, to date no combined system exists. In this study, for the first ...time a low-field open MR scanner was integrated with a static proton research beam line to test the feasibility of simultaneous irradiation and imaging. The field-of-view of the MR scanner was aligned with the beam by taking into account the Lorentz force induced beam deflection. Various imaging sequences for extremities were performed on a healthy volunteer and on a patient with a soft-tissue sarcoma of the upper arm, both with the proton beam line switched off. T1-weighted spin echo images of a tissue-mimicking phantom were acquired without beam, with energised beam line magnets and during proton irradiation. Beam profiles were acquired for the MR scanner's static magnetic field alone and in combination with the dynamic gradient fields during the acquisition of different imaging sequences. It was shown that MR imaging is feasible in the electromagnetically contaminated environment of a proton therapy facility. The observed quality of the anatomical MR images was rated to be sufficient for target volume definition and positioning. The tissue-mimicking phantom showed no visible beam-induced image degradation. The beam profiles depicted no influence due to the dynamic gradient fields of the imaging sequences. This study proves that simultaneous irradiation and in-beam MR imaging is technically feasible with a low-field MR scanner integrated with a static proton research beam line.
Current inverse treatment planning methods that optimize both catheter positions and dwell times in prostate HDR brachytherapy use surrogate linear or quadratic objective functions that have no ...direct interpretation in terms of dose-volume histogram (DVH) criteria, do not result in an optimum or have long solution times. We decrease the solution time of the existing linear and quadratic dose-based programming models (LP and QP, respectively) to allow optimizing over potential catheter positions using mixed integer programming. An additional average speed-up of 75% can be obtained by stopping the solver at an early stage, without deterioration of the plan quality. For a fixed catheter configuration, the dwell time optimization model LP solves to optimality in less than 15 s, which confirms earlier results. We propose an iterative procedure for QP that allows us to prescribe the target dose as an interval, while retaining independence between the solution time and the number of dose calculation points. This iterative procedure is comparable in speed to the LP model and produces better plans than the non-iterative QP. We formulate a new dose-volume-based model that maximizes V100% while satisfying pre-set DVH criteria. This model optimizes both catheter positions and dwell times within a few minutes depending on prostate volume and number of catheters, optimizes dwell times within 35 s and gives better DVH statistics than dose-based models. The solutions suggest that the correlation between the objective value and the clinical plan quality is weak in the existing dose-based models.
•Prediction of radiation pneumonitis (RP) in patient is still performed based on physical dose and using data from patients treated with photon therapy.•Here prediction models based on biological ...dose were developed and applied to patients treated with either photon- or proton-therapy.•It was found that the conventionally used models for RP prediction still hold in patients treated with either modality.
Radiation pneumonitis (RP) remains a major complication in non-small cell lung cancer (NSCLC) patients undergoing radiochemotherapy (RCHT). Traditionally, the mean lung dose (MLD) and the volume of the total lung receiving at least 20 Gy (V20Gy) are used to predict RP in patients treated with normo-fractionated photon therapy.
However, other models, including the actual dose-distribution in the lungs using the effective α/β model or a combination of radiation doses to the lungs and heart, have been proposed for predicting RP. Moreover, the models established for photons may not hold for patients treated with passively-scattered proton therapy (PSPT). Therefore, we here tested and validated novel predictive parameters for RP in NSCLC patient treated with PSPT.
Data on the occurrence of RP, structure files and dose-volume histogram parameters for lungs and heart of 96 NSCLC patients, treated with PSPT and concurrent chemotherapy, was retrospectively retrieved from prospective clinical studies of two international centers. Data was randomly split into a training set (64 patients) and a validation set (32 patients). Statistical analyses were performed using binomial logistic regression.
The biologically effective dose (BED) of the’lungs - GTV’ significantly predicted RP ≥ grade 2 in the training-set using both a univariate model (p = 0.019, AUCtrain = 0.72) and a multivariate model in combination with the effective α/β parameter of the heart (pBED = 0.006, pα/βeff = 0.043, AUCtrain = 0.74). However, these results did not hold in the validation-set (AUCval = 0.52 andAUCval = 0.50, respectively). Moreover, these models were found to neither outperform a model built with the MLD (p = 0.015, AUCtrain = 0.73, AUCval = 0.51), nor a multivariate model additionally including the V20Gy of the heart (pMLD = 0.039, pV20Gy,heart = 0.58, AUCtrain = 0.74, AUCval = 0.53).
Using the effective α/β parameter of the lungs and heart we achieved similar performance to commonly used models built for photon therapy, such as MLD, in predicting RP ≥ grade 2. Therefore, prediction models developed for photon RCHT still hold for patients treated with PSPT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In radiation therapy planning, uncertainties in the definition of the target volume yield a risk of underdosing the tumor. The traditional corrective action in the context of external beam ...radiotherapy (EBRT) expands the clinical target volume (CTV) with an isotropic margin to obtain the planning target volume (PTV). However, the EBRT-based PTV concept is not directly applicable to brachytherapy (BT) since it can lead to undesirable dose escalation. Here, we present a treatment plan optimization model that uses worst-case robust optimization to account for delineation uncertainties in interstitial high-dose-rate BT of the prostate. A scenario-based method was developed that handles uncertainties in index sets. Heuristics were included to reduce the calculation times to acceptable proportions. The approach was extended to account for delineation uncertainties of an organ at risk (OAR) as well. The method was applied on data from prostate cancer patients and evaluated in terms of commonly used dosimetric performance criteria for the CTV and relevant OARs. The robust optimization approach was compared against the classical PTV margin concept and against a scenario-based CTV margin approach. The results show that the scenario-based margin and the robust optimization method are capable of reducing the risk of underdosage to the tumor. As expected, the scenario-based CTV margin approach leads to dose escalation within the target, whereas this can be prevented with the robust model. For cases where rectum sparing was a binding restriction, including uncertainties in rectum delineation in the planning model led to a reduced risk of a rectum overdose, and in some cases, to reduced targetcoverage.
The online supplement is available at
https://doi.org/10.1287/ijoc.2018.0815
.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Ongoing advances in both imaging and treatment for oncology purposes have seen a significant rise in the use of not only the individual imaging modalities, but also their combination in single ...systems such as Positron Emission Tomography combined with Computed Tomography (PET-CT) and PET-MRI (Magnetic Resonance Imaging) when planning for advanced oncology treatment, the most demanding of which is proton therapy. This has identified issues in the availability of suitable materials upon which to support the patient undergoing imaging and treatment owing to the differing requirements for each of the techniques. Sandwich composites are often selected to solve this issue but there is little information regarding optimum materials for their cores. In this paper, we presented a range of materials which are suitable for such purposes and evaluated the performance for use in terms of PET signal attenuation, proton beam stopping, MRI signal shading and X-Ray CT visibility. We found that Extruded Polystyrene offers the best compromise for patient support and positioning structures across all modalities tested, allowing for significant savings in treatment planning time and delivering more efficient treatment with lower margins.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background & aims Therapy for polycystic liver is invasive, expensive, and has disappointing long-term results. Treatment with somatostatin analogues slowed kidney growth in patients with polycystic ...kidney disease (PKD) and reduced liver and kidney volume in a PKD rodent model. We evaluated the effects of lanreotide, a somatostatin analogue, in patients with polycystic liver because of autosomal-dominant (AD) PKD or autosomal-dominant polycystic liver disease (PCLD). Methods We performed a randomized, double-blind, placebo-controlled trial in 2 tertiary referral centers. Patients with polycystic liver (n = 54) were randomly assigned to groups given lanreotide (120 mg) or placebo, administered every 28 days for 24 weeks. The primary end point was the difference in total liver volume, measured by computerized tomography at weeks 0 and 24. Analyses were performed on an intention-to-treat basis. Results Baseline characteristics were comparable for both groups, except that more patients with ADPKD were assigned to the placebo group ( P = .03). The mean liver volume decreased 2.9%, from 4606 mL (95% confidence interval (CI): 547–8665) to 4471 mL (95% CI: 542–8401 mL), in patients given lanreotide. In the placebo group, the mean liver volume increased 1.6%, from 4689 mL (95% CI: 613–8765 mL) to 4895 mL (95% CI: 739–9053 mL) ( P < .01). Post hoc stratification for patients with ADPKD or PCLD revealed similar changes in liver volume, with statistically significant differences in patients given lanreotide ( P < .01 for both diseases). Conclusions In patients with polycystic liver, 6 months of treatment with lanreotide reduces liver volume.
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