Accuracy of robotic patient positioners used in ion beam therapy

BACKGROUND: In this study we investigate the accuracy of industrial six axes robots employed for patient positioning at the Heidelberg Ion Beam Therapy Center. METHODS: In total 1018 patient setups were monitored with a laser tracker and subsequently analyzed. The measurements were performed in the two rooms with a fixed horizontal beam line. Both, the 3d translational errors and the rotational errors around the three table axes were determined. RESULTS: For the first room the 3d error was smaller than 0.72 mm in 95 percent of all setups. The standard deviation of the rotational errors was at most 0.026° for all axes. For the second room Siemens implemented an improved approach strategy to the final couch positions. The 95 percent quantile of the 3d error could in this room be reduced to 0.53 mm; the standard deviation of the rotational errors was also at most 0.026°. CONCLUSIONS: Robots are very flexible tools for patient positioning in six degrees of freedom. This study proved that the robots are able to achieve clinically acceptable accuracy in real patient setups, too

Planning strategies for inter-fractional robustness in pancreatic patients treated with scanned carbon therapy

Background: Managing inter-fractional anatomy changes is a challenging task in radiotherapy of pancreatic tumors, especially in scanned carbon-ion delivery. This treatment planning study aims to focus on clinically feasible solutions, such as the beam angle selection and margin design to increase the robustness against inter-fractional uncertainties. Methods: This study included 10 patients with weekly 3D-CT imaging and physician-approved Clinical Target Volume (CTV). The study was directed to keep the CTV-coverage using six beam angle configurations in combination with different Internal Target Volume (ITV) concepts. These were: geometric-margin (symmetric 3 and 5 mm margin); range-equivalent margins with an isotropic HU replacement; and to evaluate the need of asymmetric margins the water-equivalent range path (WEPL) was determined per patient from the set of CTs. Plan optimization and forward dose calculation in each week-CT were performed with the research treatment planning system TRiP98 and the plan quality evaluated in terms of CTV coverage (V95CTV) and homogeneity dose (HCTV = D5-D95). Results: The beam geometry had a substantial impact on the target irradiation over the treatment course, with the single posterior or two beams showing the best average coverage of the CTV. The use of geometric margins for the more robust beam geometries showed acceptable results, with a V95CTV of (99.2 ± 1.2)% for the 5 mm-margin. For the non-robust configurations, due to substantial changes in the radiological depth, the use of this margin results in a V95CTV that might be below 80%, only showing improvement when the range changes are included. Conclusions: Selection of adequate beam configurations and treatment margins in ion-beam therapy of pancreatic tumors is of great importance. For a single posterior beam or two beam configurations, application of geometrical margins compensate for dose degradation induced by inter-fractional anatomy changes for the majority of the analyzed treatment fractions

Multivariate error modeling and uncertainty quantification using importance (re-)weighting for Monte Carlo simulations in particle transport

Fast and accurate predictions of uncertainties in the computed dose are crucial for the determination of robust treatment plans in radiation therapy. This requires the solution of particle transport problems with uncertain parameters or initial conditions. Monte Carlo methods are often used to solve transport problems especially for applications which require high accuracy. In these cases, common non-intrusive solution strategies that involve repeated simulations of the problem at different points in the parameter space quickly become infeasible due to their long run-times. Intrusive methods however limit the usability in combination with proprietary simulation engines. In our previous paper [51], we demonstrated the application of a new non-intrusive uncertainty quantification approach for Monte Carlo simulations in proton dose calculations with normally distributed errors on realistic patient data. In this paper, we introduce a generalized formulation and focus on a more in-depth theoretical analysis of this method concerning bias, error and convergence of the estimates. The multivariate input model of the proposed approach further supports almost arbitrary error correlation models. We demonstrate how this framework can be used to model and efficiently quantify complex auto-correlated and time-dependent errors.Comment: 26 pages, 10 figures, [v2]: corrected title of figure

Influence of 68Ga-DOTATOC on sparing of normal tissue for radiation therapy of skull base meningioma: differential impact of photon and proton radiotherapy

Background: To evaluate the impact of 68Ga-DOTATOC-PET on treatment planning and sparing of normal tissue in the treatment of skull base meningioma with advanced photons and protons. Methods: From the institutional database consisting of 507 skull base meningiomas 10 patients were chosen randomly for the present analysis. Target volume definition was performed based on CT and MRI only, as well as with additional 68Ga-DOTATOC-PET. Treatment plans were performed for Intensity Modulated Radiotherapy (IMRT) and proton therapy using active raster scanning on both target volumes. We calculated doses to relevant organs at risk (OAR), conformity indices as well as differences in normal tissue sparing between both radiation modalities based on CT/MRI planning as well as CT/MRI/PET planning. Results: For photon treatment plans, PET-based treatment plans showed a reduction of brain stem Dmax and Dmedian for different levels of total dose. At the optic chiasm, use of 68Ga-DOTATOC significantly reduces Dmax; moreover, the Dmedian is reduced in most cases, too. For both right and left optic nerve, reduction of dose by addition of 68Ga-DOTATOC-PET is minimal and depends on the anatomical location of the meningioma. In protons, the impact of 68Ga-DOTATOC-PET is minimal compared to photons. Conclusion: Addition of 68Ga-DOTATOC-PET information into treatment planning for skull base meningiomas has a significant impact on target volumes. In most cases, PET-planning leads to significant reductions of the treatment volumes. Subsequently, reduced doses are applied to OAR. Using protons, the benefit of additional PET is smaller since target coverage is more conformal and dose to OAR is already reduced compared to photons. Therefore, PET-imaging has the greatest margin of benefit in advanced photon techniques, and combination of PET-planning and high-precision treatment leads to comparable treatment plans as with protons

Significance of intra-fractional motion for pancreatic patients treated with charged particles

Background; Uncertainties associated with the delivery of treatment to moving organs might compromise the accuracy of treatment. This study explores the impact of intra-fractional anatomical changes in pancreatic patients treated with charged particles delivered using a scanning beam. The aim of this paper is to define the potential source of uncertainties, quantify their effect, and to define clinically feasible strategies to reduce them. Methods: The study included 14 patients treated at our facility with charged particles (protons or 12C) using intensity modulated particle therapy (IMPT). Treatment plans were optimized using the Treatment Planning System (TPS) Syngo® RT Planning. The pre-treatment dose distribution under motion (4D) was simulated using the TPS TRiP4D and the dose delivered for some of the treatment fractions was reconstructed. The volume receiving at least 95% of the prescribed dose (V95CTV) and the target dose homogeneity were evaluated. The results from the 4D dose calculations were compared with dose distributions in the static case and its variation correlated with the internal motion amplitude and plan modulation, through the Pearson correlation coefficient, as well the significant p-value. The concept of the modulation index (MI) was introduced to assess the degree of modulation of IMPT plans, through the quantification of intensity gradients between neighboring pencil beams. Results: The induced breathing motion together with dynamic beam delivery results in an interplay effect, which affects the homogeneity and target coverage of the dose distribution. This effect is stronger (∆V95CTV > 10%) for patients with tumor motion amplitude above 5 mm and a highly modulated dose distribution between and within fields. The MI combined with the internal motion amplitude is shown to correlate with the target dose degradation and a lack of plan robustness against range and positioning uncertainties. Conclusions: Under internal motion the use of inhomogeneous plans results in a decrease in the dose homogeneity and target coverage of dose distributions in comparison to the static case. Plan robustness can be improved by using multiple beams and avoiding beam entrance directions susceptible to density changes. 4D dose calculations support the selection of the most suitable plan for the specific patient’s anatomy

First experiences with the implementation of the European standard EN 62304 on medical device software for the quality assurance of a radiotherapy unit

BACKGROUND: According to the latest amendment of the Medical Device Directive standalone software qualifies as a medical device when intended by the manufacturer to be used for medical purposes. In this context, the EN 62304 standard is applicable which defines the life-cycle requirements for the development and maintenance of medical device software. A pilot project was launched to acquire skills in implementing this standard in a hospital-based environment (in-house manufacture). METHODS: The EN 62304 standard outlines minimum requirements for each stage of the software life-cycle, defines the activities and tasks to be performed and scales documentation and testing according to its criticality. The required processes were established for the pre-existent decision-support software FlashDumpComparator (FDC) used during the quality assurance of treatment-relevant beam parameters. As the EN 62304 standard implicates compliance with the EN ISO 14971 standard on the application of risk management to medical devices, a risk analysis was carried out to identify potential hazards and reduce the associated risks to acceptable levels. RESULTS: The EN 62304 standard is difficult to implement without proper tools, thus open-source software was selected and integrated into a dedicated development platform. The control measures yielded by the risk analysis were independently implemented and verified, and a script-based test automation was retrofitted to reduce the associated test effort. After all documents facilitating the traceability of the specified requirements to the corresponding tests and of the control measures to the proof of execution were generated, the FDC was released as an accessory to the HIT facility. CONCLUSIONS: The implementation of the EN 62304 standard was time-consuming, and a learning curve had to be overcome during the first iterations of the associated processes, but many process descriptions and all software tools can be re-utilized in follow-up projects. It has been demonstrated that a standards-compliant development of small and medium-sized medical software can be carried out by a small team with limited resources in a clinical setting. This is of particular relevance as the upcoming revision of the Medical Device Directive is expected to harmonize and tighten the current legal requirements for all European in-house manufacturers

Ion range measurements using fluorescent nuclear track detectors

Fluorescent nuclear track detectors (FNTDs) show excellent detection properties for heavy charged particles and have, therefore, been investigated in this study in terms of their potential for in-vivo range measurements. We irradiated FNTDs with protons as well as with C, Mg, S, Fe and Xe ion beams (3 – 9 MeV/u) over a broad range of fluences (4.5e5 – 1.0e11 per cm²) with the detectors’ optical c-axis positioned perpendicular to the beam direction. All measured ion ranges (for single track as well as track bulk intensity irradiations) deviate less than 3% from tabulated SRIM data, independent of particle type, energy, fluence and linear energy transfer. Proton irradiation of detectors placed inside a polymethyl methacrylate (PMMA) phantom at the Heidelberg Ion-Beam Therapy Center showed promising results for future in-vivo FNTD applications