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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.

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.

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.

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.

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.

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