W. Enghardt

In-beam PET measurements of β+ radioactivity induced by proton beams

Our first in-beam PET measurements of the β+ activation induced by proton irradiation are presented. Monoenergetic proton beams in the energy and intensity range suited for the treatment of deep-seated tumours were delivered by the synchrotron of the Gesellschaft fur Schwerionenforschung Darmstadt (GSI). They were stopped in PMMA blocks placed in the centre of the field of view of the positron camera that is installed in the heavy ion tumour treatment facility at GSI. The β+ activity signal was found to be three times larger than that produced by carbon ions at the same range and applied physical dose. The reconstructed spatial β+ activity distributions were analysed and compared with the production of positron emitters predicted by a calculation based on experimental cross-sections and on the proton flux given by the FLUKA Monte Carlo code. The shape of the depth-activity profiles was well reproduced by the model and the correlation with the proton range and the depth-dose distributions was carefully investigated. Despite the non-trivial range determination from the β+ activity distribution in the proton case, our experimental investigation supports the feasibility of an in situ proton therapy monitoring by means of in-beam PET, as already clinically implemented for the monitoring of carbon ion therapy at GSI Darmstadt.

On the detector arrangement for in-beam PET for hadron therapy monitoring

In-beam positron emission tomography (in-beam PET) is currently the only method for an in situ monitoring of highly tumour-conformed charged hadron therapy. At the experimental carbon ion tumour therapy facility, running at the Gesellschaft für Schwerionenforschung, Darmstadt, Germany, all treatments have been monitored by means of a specially adapted dual-head PET scanner. The positive clinical impact of this project triggered the construction of a hospital-based hadron therapy facility, with in-beam PET expected to monitor more delicate radiotherapeutic situations. Therefore, we have studied possible in-beam PET improvements by optimizing the arrangement of the gamma-ray detectors. For this, a fully 3D, rebinning-free, maximum likelihood expectation maximization algorithm applicable to several closed-ring or dual-head tomographs has been developed. The analysis of beta(+)-activity distributions simulated from real-treatment situations and detected with several detector arrangements allows us to conclude that a dual-head tomograph with narrow gaps yields in-beam PET images with sufficient quality for monitoring head and neck treatments. For monitoring larger irradiation fields, e.g. treatments in the pelvis region, a closed-ring tomograph was seen to be highly desirable. Finally, a study of the space availability for patient and bed, tomograph and beam portal proves the implementation of a closed-ring detector arrangement for in-beam PET to be feasible.

Radiotherapy for chordomas and low-grade chondrosarcomas of the skull base with carbon ions

PURPOSE Compared to photon irradiation, carbon ions provide physical and biologic advantages that may be exploited in chordomas and chondrosarcomas. METHODS AND MATERIALS 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). RESULTS 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. CONCLUSION 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.

Experimental study on the feasibility of in-beam PET for accurate monitoring of proton therapy

Positron emission tomography (PET) is currently the only feasible method for in-situ and noninvasive three-dimensional monitoring of the precision of the treatment in highly conformal ion therapy. Its positive clinical impact has been proven for fractionated carbon ion therapy of head and neck (H&N) tumors at the experimental facility at the Gesellschaft fur Schwerionenforschung (GSI), Darmstadt, Germany. Following previous promising experiments, the possible extension of the method to the monitoring of proton therapy has been investigated further in extensive in-beam measurements at GSI. Millimeter accuracy for verification of the lateral field position and for the most challenging issue of range monitoring has been demonstrated in monoenergetic and spread-out Bragg-peak (SOBP) proton irradiation of polymethyl methacrylate (PMMA) targets. The irradiation of an inhomogeneous phantom with tissue equivalent inserts in combination with further dynamic analysis has supported the extension of such millimeter precision to real clinical cases, at least in regions of interest for low perfused tissues. All the experimental investigations have been reproduced by the developed modeling rather well. This indicates the possible extraction of valuable clinical information as particle range in-vivo, irradiation field position, and even local deviations from the dose prescription on the basis of the comparison between measured and predicted activity distributions. Hence, the clinical feasibility of in-beam PET for proton therapy monitoring is strongly supported.

The modelling of positron emitter production and PET imaging during carbon ion therapy

At the carbon ion therapy facility of GSI Darmstadt in-beam positron emission tomography (PET) is used for imaging the beta+-activity distributions which are produced via nuclear fragmentation reactions between the carbon ions and the atomic nuclei of the irradiated tissue. On the basis of these PET images the quality of the irradiation, i.e. the position of the field, the particle range in vivo and even local deviations between the planned and the applied dose distribution, can be evaluated. However, for such an evaluation the measured beta+-activity distributions have to be compared with those predicted from the treatment plan. The predictions are calculated as follows: a Monte Carlo event generator produces list mode data files of the same format as the PET scanner in order to be processed like the measured ones for tomographic reconstruction. The event generator models the whole chain from the interaction of the projectiles with the target, i.e. their stopping and nuclear reactions, the production and the decay of positron emitters, the motion of the positrons as well as the propagation and the detection of the annihilation photons. The steps of the modelling, the experimental validation and clinical implementation are presented.

Dose quantification from in-beam positron emission tomography

Positron emission tomography (PET) imaging of the radioactivity distributions induced by therapeutic irradiation is at present the only feasible method for an in situ and non-invasive monitoring of radiooncology treatments with ion beams. The clinical implementation of this imaging technology at the experimental carbon ion therapy facility at the Gesellschaft für Schwerionenforschung (GSI) at Darmstadt, Germany is outlined and an interactive approach for a PET guided quantification of local dose deviations with respect to the treatment plan is presented.

Dose-dependent biological damage of tumour cells by laser-accelerated proton beams

We report on the first irradiation of in vitro tumour cells with laser-accelerated proton pulses showing dose-dependent biological damage. This experiment, paving the way for future radiobiological studies with laser-accelerated protons, demonstrates the simultaneous availability of all the components indispensable for systematic radiobiological studies: a laser-plasma accelerator providing proton spectra with maximum energy exceeding 15MeV and applicable doses of a few Gy within a few minutes; a beam transport and filtering system; an in-air irradiation site; and a dosimetry system providing both online dose monitoring and absolute dose information applied to the cell sample and the full infrastructure for analysing radiation-induced damage in cells.

Comparative study of scintillators for PET/CT detectors

A growing interest in the development of dual modality PET/CT scanners prompts the comparative study of numerous scintillators to select the best one, which could be used simultaneously in PET detectors working in the pulsing mode and in the CT detectors working in the current mode. In the comparative measurements, done in the same experimental conditions, various samples of BGO, GSO, GSO:Ce, Zr, LGSO, LSO, LYSO, MLS, LaCl3, LaBr3 and CWO scintillators were tested. The measurements covered a determination of the light output, energy resolution, non-proportionality of the light yield, decay times of the light pulses and for the selected crystals their time resolution for 511 keV annihilation quanta. Moreover, a comparative study of afterglow, induced by 60 keV gamma-rays from a strong 241Am source (13.9 GBq), was done in the second range of time. The LSO-like crystals are the best in the PET scanners application. However, they do not fit to the CT requirements, due to a high afterglow. The studies conclude that besides of the well known BGO, only GSO:Ce and most likely LaBr3 might be considered for the simultaneous PET/CT detector

Positron emission tomography for quality assurance of cancer therapy with light ion beams

Positron emission tomography (PET) offers the possibility of in-situ monitoring the tumour treatment with light ion beams by means of imaging the spatial distribution of β − -activity that is produced as a byproduct of the therapeutic irradiation via nuclear fragmentation reactions between the projectiles and the atomic nuclei of the tissue within the target volume. The implementation of this PET technique at the experimental tumour therapy facility at the Gesellschaft fur Schwerionenforschung (GSI) in Darmstadt and first results of its clinical application are presented.

Bestrahlung von Schädelbasistumoren mit Kohlenstoffionen bei der GSI Erste klinische Ergebnisse und zukünftige Perspektiven

Hintergrund: 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.Background: 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.