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ABSTRACT: Strahlenbiologische und medizinphysikalische Untersuchungen versprechen Vorteile bei der Patientenbestrahlung mit schweren
Ionen. Die vorliegende Arbeit berichtet über die ersten klinischen Ergebnisse bei 45 Patienten mit Schädelbasistumoren, die
zwischen Dezember 1997 und September 1999 am Schwerionensynchroton der Gesellschaft für Schwerionenforschung (GSI), Darmstadt,
mit Kohlenstoffionen bestrahlt wurden.
Patienten und Methode: Die Patienten (23 Frauen, 22 Männer) waren im Mittel 48 (18 bis 80) Jahre alt und litten an Chordomen (17), Chondrosarkomen
(zehn) und anderen Tumoren der Schädelbasis. Erstmalig kamen das intensitätsmodulierte Rasterscan-Verfahren und die Online-Therapiekontrolle
mittels Positronenmissionstomographie am Patienten zum Einsatz. Computertomographische Aufnahmen waren Grundlage für die dreidimensionale
Strahlentherapieplanung. Patienten mit Chordomen und Chondrosarkomen erhielten eine fraktionierte Bestrahlung mit Kohlenstoffionen
(mediane Gesamtdosis 60 GyE) an 20 konsekutiven Tagen. Bei den anderen Tumorhistologien wurde nach fraktionierter stereotaktischer
Radiotherapie ein Kohlenstoffionenboost von 15 bis 18 GyE auf den makroskopischen Tumor appliziert (mediane gesamtdosis 63
GyE).
Ergebnisse: Der mittlere Nachbeobachtungszeitraum betrug neun Monate. Die Bestrahlung wurde gut toleriert. Die lokale Kontrollrate über
alle Histologien hinweg lag nach einem Jahr bei 94%. Zur partiellen Tumorremission kam es bei sieben Patienten (15,5%). Ein
Patient (2,2%) ist verstorben. Es wurden bei keinem Patienten schwere radiogene Nebenwirkungen (> II° Common Toxicity Criteria)
beobachtet. Bislang ist bei keinem Patienten ein Rezidiv im Behandlungsvolumen aufgetreten.
Schlussfolgerung: Die klinische Wirksamkeit und die technische Durchführbarkeit diese neuen Therapieverfahrens konnten eindeutig belegt werden.
Um den klinische Stellenwert der Bestrahlungsmodalitäten mit Protonen und Ionen weiter zu beleuchten, sind Untersuchungen
mit größeren Patientenzahlen notwendig. Als konsequente Fortführung des Projektes ist der Bau eines ausschließlich klinisch
genutzten Teilchenbeschleunigers in Heidelberg geplant.
Radiobiological and physical examinations suggest clinical advantages of heavy ion irradiation. We report the result of 23
women and 22 men (median age 48 years) with skull base tumors irradiated with carbon ion beams at the Gesellschaft für Schwerionenforschung
(GSI), Darmstadt, from December 1997 until September 1999.
Patients and Methods: The study included patients with chordomas (17), chondrosarcomas (10) and other skull base tumors (Table 1). It is the first
time that the intensity-controlled rasterscan-technique and the application of positron-emission tomography (PET) for quality
assurance was used. All patients had computed tomography for three-dimensional-treatment planning (Figure 1). Patients with
chordomas and chondrosarcomas underwent fractionated carbon ion irradiation in 20 consecutive days (median total dose 60 GyE).
Other histologies were treated with carbon ion boost of 15 to 18 GyE delivered to the macroscopeic tumor after fractionated
stereotatic radiotherapy (median total dose 63 GyE).
Results: Mean follow-up was 9 months. Irradiation was well tolerated by all patients. Partial tumor remission was seen in 7 patients
(15,5%) (Figure 2). One-year local control rate was 94%. One patient (2,2%) deceased. No severe toxicity and no local recurrence
within the treated volume were observed.
Conclusion Clinical effectiveness and technical feasibility of this modality could clearly be demonstrated in our study. To evaluate
the clinical relevance of the different beam modalities studies with larger patient numbers are necessary. To continue our
project a new heavy ion acclerator exclusively for clinical use is planed to be constructed in Heidelberg.
Schlüsselwörter: Schädelbasis–Kohlenstoffionen–Schwerionentherapie–Strahlentherapie–GSIKey Words: Skull base–Carbon ion–Heavy ion Therapy–Radiotherapy–GSI
Strahlentherapie und Onkologie 04/2012; 176(5):211-216. · 3.56 Impact Factor
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ABSTRACT: Scanned ion beam therapy of intra-fractionally moving tumors requires motion mitigation. GSI proposed beam tracking and performed several experimental studies to analyse the dosimetric precision of the system for scanned carbon beams.
A beam tracking system has been developed and integrated in the scanned carbon ion beam therapy unit at GSI. The system adapts pencil beam positions and beam energy according to target motion. Motion compensation performance of the beam tracking system was assessed by measurements with radiographic films, a range telescope, a 3D array of 24 ionization chambers, and cell samples for biological dosimetry. Measurements were performed for stationary detectors and moving detectors using the beam tracking system.
All detector systems showed comparable data for a moving setup when using beam tracking and the corresponding stationary setup. Within the target volume the mean relative differences of ionization chamber measurements were 0.3% (1.5% standard deviation, 3.7% maximum). Film responses demonstrated preserved lateral dose gradients. Measurements with the range telescope showed agreement of Bragg peak depth under motion induced range variations. Cell survival experiments showed a mean relative difference of -5% (-3%) between measurements and calculations within the target volume for beam tracking (stationary) measurements.
The beam tracking system has been successfully integrated. Full functionality has been validated dosimetrically in experiments with several detector types including biological cell systems.
Radiation Oncology 01/2010; 5:61. · 2.32 Impact Factor
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Gerhard Kraft
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ABSTRACT: Heavy ion tumor therapy can reach a millimeter precision everywhere in the body and a greater biological effectiveness in radioresistant tumors compared to the normal tissue. Therefore it is possible to treat mainly resistant or otherwise inoperable tumors with ion beams with great success. In line with the excellent results achieved in a pilot project at GSI several new centers are under construction. In this article, basics of heavy ion tumor therapy are given and the clinical results of the pilot project are described.
Medizinische Monatsschrift für Pharmazeuten 09/2009; 32(9):328-34.
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ABSTRACT: Sixty years ago accelerator pioneer Robert Wilson published the paper in which he proposed using protons for cancer therapy.
The introduction of protontherapy has been very slow, but in the last 10 years the field is booming and five companies offer
turn-key centres. Fully stripped ions leave much more energy in the nuclei of the traversed cells than protons of the same
range and are thus effective in controlling radio-resistant tumours which cannot be controlled neither with X-rays nor with
protons. Paying particular attention to the European contributions, this contribution shortly reviews the history and the
developments of carbon ion therapy, a recent chapter of the “hadrontherapy” which covers also radiotherapy with proton and
neutron beams.
12/2008: pages 165-171;
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ABSTRACT: Intrafractional motion results in local over- and under-dosage in particle therapy with a scanned beam. Scanned beam delivery offers the possibility to compensate target motion by tracking with the treatment beam.
Lateral motion components were compensated directly with the beam scanning system by adapting nominal beam positions according to the target motion. Longitudinal motion compensation to mitigate motion induced range changes was performed with a dedicated wedge system that adjusts effective particle energies at isocenter.
Lateral compensation performance was better than 1% for a homogeneous dose distribution when comparing irradiations of a stationary radiographic film and a moving film using motion compensation. The accuracy of longitudinal range compensation was well below 1 mm.
Motion compensation with scanned particle beams is technically feasible with high precision.
Radiation Oncology 11/2008; 3:34. · 2.32 Impact Factor
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ABSTRACT: This paper reviews the European activities in the field of tumour therapy with beams which have a Radio Biological Effectiveness (RBE) larger than 1. Initially neutron beams have been used. Then charged pions promised better cure rates so that their use was pursued in the framework of the ;Piotron' project at the Paul Scherrer Institute (Switzerland). However both approaches did not meet the expectations and in the 80s the EULIMA project became the flagship of these attempts to improve the effects of the delivery of radiation doses of large RBE with respect to photons, electrons and even protons. The EULIMA ion accelerator was never built and it took more than ten years to see the approval, in Heidelberg and Pavia, of the construction of the HIT and CNAO ;dual' centres for carbon ions and protons. In 2008 they will start treating patients. The developments that brought to these construction projects are described together with the special features of these two facilities. The third European dual centre is being built by Siemens Medical Systems in Marburg, Germany, while other facilities have been approved but not yet fully financed in Wiener Neustadt (Austria), Lyon (France) and Uppsala (Sweden). Finally the collaboration activities of the European Network ENLIGHT are presented together with the recent involvements of European industries in the construction of turn-key dual centres and the development of a new accelerator concept for hadrontherapy, the ;cyclinac'.
Journal of Radiation Research 02/2007; 48 Suppl A:A27-41. · 1.68 Impact Factor
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ABSTRACT: Respiration-induced target motion is a major problem in intensity-modulated radiation therapy. Beam segments are delivered serially to form the total dose distribution. In the presence of motion, the spatial relation between dose deposition from different segments will be lost. Usually, this results in over- and underdosage. Besides such interplay effects between target motion and dynamic beam delivery as known from photon therapy, changes in internal density have an impact on delivered dose for intensity-modulated charged particle therapy. In this study, we have analysed interplay effects between raster scanned carbon ion beams and target motion. Furthermore, the potential of an online motion strategy was assessed in several simulations. An extended version of the clinical treatment planning software was used to calculate dose distributions to moving targets with and without motion compensation. For motion compensation, each individual ion pencil beam tracked the planned target position in the lateral as well as longitudinal direction. Target translations and rotations, including changes in internal density, were simulated. Target motion simulating breathing resulted in severe degradation of delivered dose distributions. For example, for motion amplitudes of +/-15 mm, only 47% of the target volume received 80% of the planned dose. Unpredictability of resulting dose distributions was demonstrated by varying motion parameters. On the other hand, motion compensation allowed for dose distributions for moving targets comparable to those for static targets. Even limited compensation precision (standard deviation approximately 2 mm), introduced to simulate possible limitations of real-time target tracking, resulted in less than 3% loss in dose homogeneity.
Physics in Medicine and Biology 08/2006; 51(14):3517-31. · 2.83 Impact Factor
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ABSTRACT: Intensity modulated, active beam delivery, like magnetic raster scanning, strongly relies on target immobilisation. If target motion cannot be avoided, interferences between the scanning procedure and the tumour displacement destroy the volume conformity. A prototype setup for 3D online motion compensation (3D-OMC) with a scanned particle beam is described, transferring the full potential of volume conformal irradiation to moving targets.
Radiotherapy and Oncology 01/2005; 73 Suppl 2:S77-9. · 5.58 Impact Factor
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ABSTRACT: In this presentation BANG polymer-gel dosimetry using magnetic resonance imaging (MRI) is applied to densely ionizing radiation such as carbon ion beams. BANG polymer-gels were irradiated with monoenergetic 12C ions at an energy of 205 MeVu(-1). The irradiation of the gels with doses up to 100 Gy were performed at the radiotherapy facility of the GSI, Darmstadt, Germany. For comparison with sparsely ionizing radiation data were obtained for 6 MV photon radiation, too. It was the object to examine the saturation effect for densely ionizing radiation that occurs at high values of linear energy transfer (LET). Up to now the dose response is unknown for mixed radiation fields of primary carbon ions. Therefore, to facilitate such conversions of measured MR signals into dose model calculations are proposed. This model relies only on heavy ion track structure and the experimentally determined photon response.
Radiotherapy and Oncology 01/2005; 73 Suppl 2:S99-101. · 5.58 Impact Factor
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ABSTRACT: In cancer treatment, the introduction of MeV bremsstrahlung photons has been instrumental in delivering higher doses to deep-seated tumours, while reducing the doses absorbed by the surrounding healthy tissues. Beams of protons and carbon ions have a much more favourable dose-depth distribution than photons (called 'x-rays' by medical doctors) and are the new frontiers of cancer radiation therapy. Section 2 presents the status of the first form of hadrontherapy which uses beams of 200–250 MeV protons. The central part of this review is devoted to the discussion of the physical, radiobiological and clinical bases of the use of 400 MeV u −1 carbon ions in the treatment of radio-resistant tumours. These resist irradiation with photon as well as proton beams. The following section describes the carbon ion facilities that are either running or under construction. Finally, the projects recently approved or proposed are reviewed here.
Rep. Prog. Phys. 01/2005; 68:1861-1882.
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ABSTRACT: Target motion is one of the major limitations of each high precision radiation therapy. Using advanced active beam delivery techniques, such as the magnetic raster scanning system for particle irradiation, the interplay between time-dependent beam and target position heavily distorts the applied dose distribution. This paper presents a simulation environment in which the time-dependent effect of target motion on heavy-ion irradiation can be calculated with dynamically scanned ion beams. In an extension of the existing treatment planning software for ion irradiation of static targets (TRiP) at GSI, the expected dose distribution is calculated as the sum of several sub-distributions for single target motion states. To investigate active compensation for target motion by adapting the position of the therapeutic beam during irradiation, the planned beam positions can be altered during the calculation. Applying realistic parameters to the planned motion-compensation methods at GSI, the effect of target motion on the expected dose uniformity can be simulated for different target configurations and motion conditions. For the dynamic dose calculation, experimentally measured profiles of the beam extraction in time were used. Initial simulations show the feasibility and consistency of an active motion compensation with the magnetic scanning system and reveal some strategies to improve the dose homogeneity inside the moving target. The simulation environment presented here provides an effective means for evaluating the dose distribution for a moving target volume with and without motion compensation. It contributes a substantial basis for the experimental research on the irradiation of moving target volumes with scanned ion beams at GSI which will be presented in upcoming papers.
Physics in Medicine and Biology 08/2004; 49(14):3029-46. · 2.83 Impact Factor
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ABSTRACT: This study summarizes the experience with raster scanned carbon ion radiation therapy (RT) at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt, Germany since 1997.
Between December 1997 and December 2002, 152 patients were treated at GSI with carbon ion RT. Eighty-seven patients with chordomas and low-grade chondrosarcomas of the skull base received carbon ion RT alone (median dose 60 GyE); 21 patients with unfavorable adenoid cystic carcinomas and 17 patients with spinal (n = 9) and sacrococcygeal (n = 8) chordomas and chondrosarcomas were treated with combined photon and carbon ion RT. Twelve patients received reirradiation with carbon ions with or without photon RT for recurrent tumors. Furthermore, 15 patients with skull base tumors other than chordoma and low-grade chondrosarcoma were treated with carbon ions.
Actuarial 3-year local control was 81% for chordomas, 100% for chondrosarcomas, and 62% for adenoid cystic carcinomas. Local control was obtained in 15/17 patients with spinal (8/9) and sacral (7/8) chordomas or chondrosarcomas and in 11/15 patients with skull base tumors other than chordomas and low-grade chondrosarcomas, respectively. Six of 12 patients who received reirradiation are still alive without signs of tumor progression. Common Toxicity Criteria Grade 4 or Grade 5 toxicity was not observed.
Carbon ion therapy is safe with respect to toxicity and offers high local control rates for skull base tumors such as chordomas, low-grade chondrosarcomas, and unfavorable adenoid cystic carcinomas.
International Journal of Radiation OncologyBiologyPhysics 03/2004; 58(2):631-40. · 4.11 Impact Factor
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ABSTRACT: To prospectively evaluate outcome and toxicity after carbon ion radiotherapy (RT) in chordomas and low-grade chondrosarcomas.
Between September 1998 and December 2001, 74 patients were treated for chordomas and chondrosarcomas with carbon ion RT at the "Gesellschaft für Schwerionenforschung" (GSI). Seven patients reirradiated with reduced carbon ion doses after conventional RT were excluded from the analysis, leaving 67 evaluable patients (44 chordomas and 23 chondrosarcomas) who received a full course of carbon ion therapy. Tumor-conform application of carbon ion beams was realized by intensity-controlled raster scanning with active energy variation. Three-dimensional treatment planning included intensity modulation and biological plan optimization. A median dose of 60 GyE was applied to the target volume within 20 consecutive days at a dose of 3.0 GyE per fraction.
Median follow-up was 15 months (range 3-46 months). At 3 years, actuarial local control was 100% for chondrosarcomas and 87% for chordomas, respectively. Partial tumor remission was observed in 14/44 (31%) chordoma patients and in 4/23 (17%) chondrosarcoma patients. At 3 years, actuarial overall survival was 100% for chondrosarcomas and 89% for chordomas, respectively. No severe side effects > CTC degrees III have been observed.
These data demonstrate the clinical efficiency and safety of scanning beam delivery of carbon ion beams in patients with skull base chordomas and chondrosarcomas. The observation of tumor regressions at a dose level of 60 GyE may indicate that the biological effectiveness of carbon ions in chordomas and chondrosarcomas is higher than initially estimated.
Strahlentherapie und Onkologie 10/2003; 179(9):598-605. · 3.56 Impact Factor
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ABSTRACT: PurposeTo investigate clinical feasibility and toxicity of combined photon and carbon ion radiotherapy in locally advanced adenoid cystic carcinomas (ACC) within a prospective Phase I/II trial.Methods and materialsBetween September 1998 and April 2002, 16 patients with histopathologically proven ACC and residual macroscopic tumor were treated with combined photon RT and a carbon ion boost to the macroscopic tumor. Median total tumor dose within the gross tumor volume (GTV) was 72 GyE. Photon radiation therapy (RT) consisted of fractionated stereotactic RT in 7 patients; 9 patients received stereotactic intensity-modulated RT. Carbon ion boost was delivered by intensity-controlled raster scanning at the heavy ion synchrotron (SIS) at the Heavy Ion Research Center (GSI) in Darmstadt.ResultsMedian follow-up was 12 months. Three patients developed locoregional recurrences 9, 11, and 24 months after RT, respectively. Actuarial local control rates were 80.8% and 64.6% at 1 and 3 years, respectively. Overall survival rates were 100% and 83.3% at 1 and 3 years, respectively. Acute side effects greater than Common Toxicity Criteria (CTC) Grade 2 were observed in 2 patients; no patient developed late effects > CTC Grade 2.ConclusionsCombined photon and carbon ion RT is feasible and effective in patients with locally advanced ACC. Acute and late toxicity is moderate with respect to the delivered tumor doses and in accordance with the radiobiologic modeling. A Phase III trial is designed.
International Journal of Radiation OncologyBiologyPhysics 07/2003; · 4.11 Impact Factor
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ABSTRACT: The purpose of this paper is to evaluate acute radiation-induced toxicity of carbon ion therapy.
From December 1997 to November 2000, 37 patients with chordomas and low-grade chondrosarcomas of the skull base have been treated with carbon ions at the heavy ion synchrotron (SIS) at GSI, Darmstadt. Tumor-conformal application of carbon beams was realized by intensity-controlled raster scanning in combination with pulse-to-pulse energy variation. The treatment planning procedure included a biological plan optimization. We applied a cobalt-Gray equivalent dose of 60GyE. Acute toxicity was assessed according to the common toxicity criteria (CTC).
Acute toxicity included skin reactions ( degrees I+ degrees II) in four patients, mucositis ( degrees I- degrees III) in eight patients, otitis and middle ear effusion in four, sinusitis in four, nausea/weight loss in one and edema of the temporal lobes in one patient. In two patients, preexisting neurological symptoms worsened. We did not observe acute morbidity > degrees III of normal tissues.
Scanning beam delivery of heavy charged particles is safe and reliable. No unexpected acute dose limiting toxicity was observed. With regard to toxicity, a substantial improvement compared to passive beam shaping technology is achieved.
Radiotherapy and Oncology 09/2002; 64(2):189-95. · 5.58 Impact Factor
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ABSTRACT: Compared to photon irradiation, carbon ions provide physical and biologic advantages that may be exploited in chordomas and chondrosarcomas.
Between August 1998 and December 2000, 37 patients with chordomas (n = 24) and chondrosarcomas (n = 13) were treated with carbon ion radiotherapy within a Phase I/II trial. Tumor conformal application of carbon ion beams was realized by intensity-controlled raster scanning with pulse-to-pulse energy variation. Three-dimensional treatment planning included biologic plan optimization. The median tumor dose was 60 GyE (GyE = Gy x relative biologic effectiveness).
The mean follow-up was 13 months. The local control rate after 1 and 2 years was 96% and 90%, respectively. We observed 2 recurrences outside the gross tumor volume in patients with chordomas. Progression-free survival was 100% for chondrosarcomas and 83% for chordomas at 2 years. Partial remission after carbon ion radiotherapy was observed in 6 patients. Treatment toxicity was mild.
These are the first data demonstrating the clinical feasibility, safety, and effectiveness of scanning beam delivery of ion beams in patients with skull base tumors. The preliminary results in patients with skull base chordomas and low-grade chondrosarcomas are encouraging, although the follow-up was too short to draw definite conclusions concerning outcome. In the absence of major toxicity, dose escalation might be considered.
International Journal of Radiation OncologyBiologyPhysics 06/2002; 53(1):36-42. · 4.11 Impact Factor
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ABSTRACT: A new treatment planning program was developed for the heavy ion therapy facility at GSI, which is tailored to the special
needs for an active beam delivery using a magnetic raster scanner. It also includes a biological model for the estimation
of biological effective dose for carbon ions and realizes a fully biological treatment planning. Biological effective dose
distributions and RBE maps can be displayed and assessed from the graphical user interface.
Strahlentherapie und Onkologie 04/1999; 175:12-14. · 3.56 Impact Factor
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ABSTRACT: At present, beam ion beam therapy has started to spread worldwide. In Europe and Asia, combined carbon/proton facilities are favored, but in the US, only proton centers are under construction. This development is partially due to the different funding procedures and partially due to the more complex physical and especially biologic features of the heavy ions. In this article, the basic properties of both ions are presented, and their features for therapy are outlined. This refers to the dose conformity, the general precision of the treatment, and the ability to monitor via in-beam positron emission tomography the ions range inside the patient. Then the very complex biologic features are treated, and, finally, the treatment plans are compared.
The Cancer Journal 15(4):325-32. · 3.26 Impact Factor
