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Telsemeyer J.,German Cancer Research Center | Telsemeyer J.,University of Heidelberg | Jakel O.,German Cancer Research Center | Jakel O.,University of Heidelberg | And 3 more authors.
Physics in Medicine and Biology | Year: 2012

High dose gradients are inherent to ion beam therapy. This results in high sensitivity to discrepancies between planned and delivered dose distributions. Therefore an accurate knowledge of the ion stopping power of the traversed tissue is critical. One proposed method to ensure high quality dose deposition is to measure the stopping power by ion radiography. Although the idea of imaging with highly energetic ions is more than forty years old, there is a lack of simple detectors suitable for this purpose. In this study the performance of an amorphous silicon flat-panel detector, originally designed for photon imaging, was investigated for quantitative carbon ion radiography and tomography. The flat-panel detector was exploited to measure the water equivalent thickness (WET) and water equivalent path length (WEPL) of a phantom at the Heidelberg Ion-Beam Therapy Center (HIT). To do so, the ambiguous correlation of detector signal to particle energy was overcome by active or passive variation of carbon ion beam energy and measurement of the signal-to-beam energy correlation. The active method enables one to determine the WET of the imaged object with an uncertainty of 0.5 mm WET. For tomographic WEPL measurements the passive method was exploited resulting in an accuracy of 0.01 WEPL. The developed imaging technique presents a method to measure the two-dimensional maps of WET and WEPL of phantoms with a simple and commercially available detector. High spatial resolution of 0.8 × 0.8 mm2 is given by the detector design. In the future this powerful tool will be used to evaluate the performance of the treatment planning algorithm by studying WET uncertainties. © 2012 Institute of Physics and Engineering in Medicine.


Jensen A.D.,University of Heidelberg | Winter M.,Heidelberg Ion Beam Therapy Center | Kuhn S.P.,University of Heidelberg | Debus J.,University of Heidelberg | And 2 more authors.
Radiation Oncology | Year: 2012

Purpose: To investigate repositioning accuracy in particle radiotherapy in 6 degrees of freedom (DOF) and intensity-modulated radiotherapy (IMRT, 3 DOF) for two immobilization devices (Scotchcast masks vs thermoplastic head masks) currently in use at our institution for fractionated radiation therapy in head and neck cancer patients.Methods and materials: Position verifications in patients treated with carbon ion therapy and IMRT for head and neck malignancies were evaluated. Most patients received combined treatment regimen (IMRT plus carbon ion boost), immobilization was achieved with either Scotchcast or thermoplastic head masks. Position corrections in robotic-based carbon ion therapy allowing 6 DOF were compared to IMRT allowing corrections in 3 DOF for two standard immobilization devices. In total, 838 set-up controls of 38 patients were analyzed.Results: Robotic-based position correction including correction of rotations was well tolerated and without discomfort. Standard deviations of translational components were between 0.5 and 0.8 mm for Scotchcast and 0.7 and 1.3 mm for thermoplastic masks in 6 DOF and 1.2 - 1.4 mm and 1.0 - 1.1 mm in 3 DOF respectively. Mean overall displacement vectors were between 2.1 mm (Scotchcast) and 2.9 mm (thermoplastic masks) in 6 DOF and 3.9 - 3.0 mm in 3 DOF respectively. Displacement vectors were lower when correction in 6 DOF was allowed as opposed to 3 DOF only, which was maintained at the traditional action level of > 3 mm for position correction in the pre-on-board imaging era.Conclusion: Setup accuracy for both systems was within the expected range. Smaller shifts were required when 6 DOF were available for correction as opposed to 3 DOF. Where highest possible positioning accuracy is required, frequent image guidance is mandatory to achieve best possible plan delivery and maintenance of sharp gradients and optimal normal tissue sparing inherent in carbon ion therapy. © 2012 Jensen et al; licensee BioMed Central Ltd.


Hunemohr N.,German Cancer Research Center | Krauss B.,Siemens AG | Tremmel C.,German Cancer Research Center | Ackermann B.,Heidelberg Ion Beam Therapy Center | And 4 more authors.
Physics in Medicine and Biology | Year: 2014

We present an experimental verification of stopping-power-ratio (SPR) prediction from dual energy CT (DECT) with potential use for dose planning in proton and ion therapy. The approach is based on DECT images converted to electron density relative to watere, w and effective atomic number Zeff. To establish a parameterization of the I-value by Zeff, 71 tabulated tissue compositions were used. For the experimental assessment of the method we scanned 20 materials (tissue surrogates, polymers, aluminum, titanium) at 80/140Sn kVp and 100/140Sn kVp (Sn: Additional tin filtration) and computed the ee, w and Zeff with a purely image based algorithm. Thereby, we found that ee, w (Zeff) could be determined with an accuracy of 0.4% (1.7%) for the tissue surrogates with known elemental compositions. SPRs were predicted from DECT images for all 20 materials using the presented approach and were compared to measured water-equivalent path lengths (closely related to SPR). For the tissue surrogates the presented DECT approach was found to predict the experimental values within 0.6%, for aluminum and titanium within an accuracy of 1.7% and 9.4% (from 16-bit reconstructed DECT images). © 2014 Institute of Physics and Engineering in Medicine.


Paganetti H.,Massachusetts General Hospital | Paganetti H.,Harvard University | Goitein M.,Harvard University | Parodi K.,Heidelberg Ion Beam Therapy Center
Radiotherapy and Oncology | Year: 2010

Background and purpose: Antiprotons have been suggested as a possibly superior modality for radiotherapy, due to the energy released when they annihilate, which enhances the Bragg peak and introduces a high-LET component to the dose. Previous studies have focused on small-diameter near-monoenergetic antiproton beams. The goal of this work was to study more clinically relevant beams. Methods: We used Monte Carlo techniques to simulate 120 and 200 MeV beams of both antiprotons and protons of 1 × 1 and 10 × 10 cm2 areas, impinging on water. Results: An annihilating antiproton loses little energy locally; most goes into long-range secondary particles. When clinically typical field sizes are considered, these particles create a substantial dose halo around the primary field and degrade its lateral fall-off. Spreading the dose in depth further intensifies these effects. Conclusions: The physical dose distributions of spread-out antiproton beams of clinically relevant size (e.g. 10 × 10 cm2 area) are substantially inferior to those of proton beams, exhibiting a dose halo and broadened penumbra. Studies on the value of antiproton beams, taking radiobiological effectiveness into account, need to assess such realistic beams and determine whether their inferior dose distributions do not undermine the potential value of antiprotons for all but the smallest fields. © 2009 Elsevier Ireland Ltd. All rights reserved.


Schwaab J.,Heidelberg Ion Beam Therapy Center | Schwaab J.,University of Heidelberg | Brons S.,Heidelberg Ion Beam Therapy Center | Fieres J.,Siemens AG | And 2 more authors.
Physics in Medicine and Biology | Year: 2011

Scanned ion pencil beams carry a low-dose envelope which can extend up to several centimeters from the individual beam central axis. Depending on the energy and species of the beam, this halo consists mainly of secondary particles produced by nuclear interactions in the target or of particles undergoing multiple Coulomb scattering in the beam line components. This halo is often neglected by single Gaussian beam modeling in current treatment planning systems. One possibility of improving the accuracy of treatment planning is to upgrade the used pencil beam models by adding a description of the low-dose envelope. But at the same time it is crucial to keep the calculation time and the complexity for treatment planning in reasonable limits. As a first approach we measured the lateral beam profiles of scanned proton and carbon ion pencil beams at different energies and depths in water and air at the Heidelberg Ion Beam Therapy Center. Then we tried to describe their beam halo by adding a supplementary Gaussian function to the standard single Gauss modeling which is used at the moment by our treatment planning systems. This analysis helped to identify trends in the parameters describing the lateral beam broadening to support its modeling. Finally, it is shown that the accuracy of treatment planning could be improved by the proposed upgrade of the pencil beam model. In particular, the presented experimental data can be either used directly as input for dose calculation or serve for representative comparison with the results of calculation models such as Monte Carlo simulations for the generation of lateral basic data to be input in upgraded beam models of treatment planning systems. © 2011 Institute of Physics and Engineering in Medicine.


Karger C.P.,German Cancer Research Center | Jakel O.,German Cancer Research Center | Jakel O.,Heidelberg Ion Beam Therapy Center | Palmans H.,National Physical Laboratory United Kingdom | Kanai T.,Gunma University
Physics in Medicine and Biology | Year: 2010

Recently, ion beam radiotherapy (including protons as well as heavier ions) gained considerable interest. Although ion beam radiotherapy requires dose prescription in terms of iso-effective dose (referring to an iso-effective photon dose), absorbed dose is still required as an operative quantity to control beam delivery, to characterize the beam dosimetrically and to verify dose delivery. This paper reviews current methods and standards to determine absorbed dose to water in ion beam radiotherapy, including (i) the detectors used to measure absorbed dose, (ii) dosimetry under reference conditions and (iii) dosimetry under non-reference conditions. Due to the LET dependence of the response of films and solid-state detectors, dosimetric measurements are mostly based on ion chambers. While a primary standard for ion beam radiotherapy still remains to be established, ion chamber dosimetry under reference conditions is based on similar protocols as for photons and electrons although the involved uncertainty is larger than for photon beams. For non-reference conditions, dose measurements in tissue-equivalent materials may also be necessary. Regarding the atomic numbers of the composites of tissue-equivalent phantoms, special requirements have to be fulfilled for ion beams. Methods for calibrating the beam monitor depend on whether passive or active beam delivery techniques are used. QA measurements are comparable to conventional radiotherapy; however, dose verification is usually single field rather than treatment plan based. Dose verification for active beam delivery techniques requires the use of multi-channel dosimetry systems to check the compliance of measured and calculated dose for a representative sample of measurement points. Although methods for ion beam dosimetry have been established, there is still room for developments. This includes improvement of the dosimetric accuracy as well as development of more efficient measurement techniques. © 2010 Institute of Physics and Engineering in Medicine Printed in the UK.


Gillmann C.,University of Heidelberg | Jakel O.,University of Heidelberg | Jakel O.,Heidelberg Ion Beam Therapy Center | Jakel O.,German Cancer Research Center | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2014

Purpose To compare the relative biological effectiveness (RBE)-weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time of 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cmÂ(the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cmÂwith the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD5) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a comparable photon-treated collective using the same dosimetric variable as in the present study. © 2014 Elsevier Inc. All rights reserved.


Jensen A.D.,University of Heidelberg | Poulakis M.,University of Heidelberg | Nikoghosyan A.V.,University of Heidelberg | Chaudhri N.,Heidelberg Ion Beam Therapy Center | And 4 more authors.
Radiotherapy and Oncology | Year: 2015

Background Treatment of local relapse in adenoid cystic carcinoma (ACC) following prior radiation remains a challenge: without the possibility of surgical salvage patients face the choice between palliative chemotherapy and re-irradiation. Chemotherapy yields response rates around 30% and application of tumouricidal doses is difficult due to proximity of critical structures. Carbon ion therapy (C12) is a promising method to minimize side-effects and maximize re-treatment dose in this indication. We describe our initial results for re-irradiation in heavily pre-treated ACC patients. Methods Patients treated with carbon ion therapy between 04/2010 and 05/2013 (N = 52 pts, median age: 54 a) were retrospectively evaluated regarding toxicity (NCI CTC v.4), tumour response (RECIST) and control rates. 48 pts (92.3%) received carbon ions only, 4 pts received IMRT plus C12. Results 4 pts were treated following R1-resection, 43 pts for inoperable local relapse. Most common tumour sites were paranasal sinus (36.5%), parotid (19.2%), and base of skull (17.3%). Pts received a median dose of 51 GyE C12/63 Gy BED and cumulative dose of 128 Gy BED [67-182 Gy] after a median RT-interval of 61 months. Median target volume was 93 ml [9-618 ml]. No higher-grade (>°II) acute reactions were observed, 7 pts showed blood-brain-barrier changes (°I/II: 8 pts; °III: 2 pts), 1 pt corneal ulceration, xerophthalmia 7 pts, °IV bleeding 1 pt, tissue necrosis 2 pts, otherwise no significant late reactions. Objective response rate (CR/PR) was 56.6%. With a median follow-up of 14 months [1-39 months] local control and distant control at 1a are 70.3% and 72.6% respectively. Of the 18 pts with local relapse, 13 pts have recurred in-field, 1 pt at the field edge, 3 pts out of field, and one in the dose gradient. Conclusion Despite high applied doses, C12 re-irradiation shows moderate side-effects, response rates even in these heavily pre-treated patients are encouraging and present a good alternative to palliative chemotherapy. Though most local recurrences occur within the high-dose area, further dose escalation should be viewed with caution. © 2015 The Authors. Published by Elsevier Ireland Ltd.


Kamp F.,Yale University | Kamp F.,TU Munich | Cabal G.,Ludwig Maximilians University of Munich | Mairani A.,Medical Physics Unit | And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2015

Purpose The physical and biological differences between heavy ions and photons have not been fully exploited and could improve treatment outcomes. In carbon ion therapy, treatment planning must account for physical properties, such as the absorbed dose and nuclear fragmentation, and for differences in the relative biological effectiveness (RBE) of ions compared with photons. We combined the mechanistic repair-misrepair-fixation (RMF) model with Monte Carlo-generated fragmentation spectra for biological optimization of carbon ion treatment plans. Methods and Materials Relative changes in double-strand break yields and radiosensitivity parameters with particle type and energy were determined using the independently benchmarked Monte Carlo damage simulation and the RMF model to estimate the RBE values for primary carbon ions and secondary fragments. Depth-dependent energy spectra were generated with the Monte Carlo code FLUKA for clinically relevant initial carbon ion energies. The predicted trends in RBE were compared with the published experimental data. Biological optimization for carbon ions was implemented in a 3-dimensional research treatment planning tool. Results We compared the RBE and RBE-weighted dose (RWD) distributions of different carbon ion treatment scenarios with and without nuclear fragments. The inclusion of fragments in the simulations led to smaller RBE predictions. A validation of RMF against measured cell survival data reported in published studies showed reasonable agreement. We calculated and optimized the RWD distributions on patient data and compared the RMF predictions with those from other biological models. The RBE values in an astrocytoma tumor ranged from 2.2 to 4.9 (mean 2.8) for a RWD of 3 Gy(RBE) assuming (α/β)X = 2 Gy. Conclusions These studies provide new information to quantify and assess uncertainties in the clinically relevant RBE values for carbon ion therapy based on biophysical mechanisms. We present results from the first biological optimization of carbon ion radiation therapy beams on patient data using a combined RMF and Monte Carlo damage simulation modeling approach. The presented method is advantageous for fast biological optimization. © 2015 Elsevier Inc. All rights reserved.


Bauer J.,Heidelberg Ion Beam Therapy Center | Bauer J.,University of Heidelberg | Unholtz D.,Heidelberg Ion Beam Therapy Center | Unholtz D.,University of Heidelberg | And 5 more authors.
Physics in Medicine and Biology | Year: 2013

We report on the experimental campaign carried out at the Heidelberg Ion-Beam Therapy Center (HIT) to optimize the Monte Carlo (MC) modelling of proton-induced positron-emitter production. The presented experimental strategy constitutes a pragmatic inverse approach to overcome the known uncertainties in the modelling of positron-emitter production due to the lack of reliable cross-section data for the relevant therapeutic energy range. This work is motivated by the clinical implementation of offline PET/CT-based treatment verification at our facility. Here, the irradiation induced tissue activation in the patient is monitored shortly after the treatment delivery by means of a commercial PET/CT scanner and compared to a MC simulated activity expectation, derived under the assumption of a correct treatment delivery. At HIT, the MC particle transport and interaction code FLUKA is used for the simulation of the expected positron-emitter yield. For this particular application, the code is coupled to externally provided cross-section data of several proton-induced reactions. Studying experimentally the positron-emitting radionuclide yield in homogeneous phantoms provides access to the fundamental production channels. Therefore, five different materials have been irradiated by monoenergetic proton pencil beams at various energies and the induced β+ activity subsequently acquired with a commercial full-ring PET/CT scanner. With the analysis of dynamically reconstructed PET images, we are able to determine separately the spatial distribution of different radionuclide concentrations at the starting time of the PET scan. The laterally integrated radionuclide yields in depth are used to tune the input cross-section data such that the impact of both the physical production and the imaging process on the various positron-emitter yields is reproduced. The resulting cross-section data sets allow to model the absolute level of measured β+ activity induced in the investigated targets within a few per cent. Moreover, the simulated distal activity fall-off positions, representing the central quantity for treatment monitoring in terms of beam range verification, are found to agree within 0.6 mm with the measurements at different initial beam energies in both homogeneous and heterogeneous targets. © 2013 Institute of Physics and Engineering in Medicine.

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