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In the field of radiotherapy Monte Carlo (MC) particle transport calculations are recognized for their superior accuracy in predicting dose and fluence distributions in patient geometries compared to analytical algorithms which are generally used for treatment planning due to their shorter execution time. In the present work, a newly-developed MC-based treatment planning (MCTP) tool for proton therapy is proposed to support treatment planning studies and research applications. It allows for single-field and simultaneous multiple-field optimization in realistic treatment scenarios and is based on the MC code FLUKA. Relative biological effectiveness (RBE)-weighted dose is optimized either with the common approach using a constant RBE of 1.1 or using a variable RBE according to radiobiological input tables. A validated reimplementation of the local effect model was used in this work to generate radiobiological input tables. Examples of treatment plans in water phantoms and in patient-CT geometries are presented for clinical treatment parameters as used at the CNAO (Italian Center for Hadrontherapy) facility. To conclude, a versatile MCTP tool for proton therapy was developed and validated for realistic patient treatment scenarios and dosimetric measurements. It is aimed to be used in future for research and to support treatment planning at state-of-the-art ion beam therapy facilities.

The multi-purpose particle interaction and transport code FLUKA is integral part of all radiation protection studies for the design and operation of the Large Hadron Collider (LHC) at CERN. It is one of the very few codes available for this type of calculations which is capable to calculate in one and the same simulation proton-proton and heavy ion collisions at LHC energies as well as the entire hadronic and electromagnetic particle cascade initiated by secondary particles in detectors and beam-line components from TeV energies down to energies of thermal neutrons. The present paper reviews these capabilities of FLUKA in giving details of relevant physics models along with examples of radiation protection studies for the LHC such as shielding studies for underground areas occupied by personnel during LHC operation and the simulation of induced radioactivity around beam loss points. Integral part of the FLUKA development is a careful benchmarking of specific models as well as the code performance in complex, real life applications which is demonstrated with examples of studies relevant to radiation protection at the LHC.

An independent assessment of the dose delivery in ion therapy can be performed using positron emission tomography (PET). For that a distribution of positron emitters which appear as the result of interaction between ions of the therapeutic beam and the irradiated tissue is measured during or after the irradiation. Three concepts for PET monitoring implemented in various therapy facilities are considered in this paper. The in-beam PET concept relies on the PET measurement performed simultaneously to the irradiation by means of a PET scanner which is completely integrated into the irradiation site. The in-room PET concept allows measurement immediately after irradiation by a standalone PET scanner which is installed very close to the irradiation site. In the off-line PET scenario themeasurement is performed by means of a standalone PET/CT scanner 10–30 min after the irradiation. These three concepts were evaluated according to image quality criteria, integration costs, and their influence onto the workflow of radiotherapy. In-beam PET showed the best performance. However, the integration costs were estimated as very high for this modality. Moreover, the performance of in-beam PET depends heavily on type and duty cycle of the accelerator. The in-room PET is proposed for planned therapy 5 Present address: Philips Research, HTC11, 5656 AE Eindhoven, The Netherlands. 0031-9155

In-beam PET has become a quality assurance tool providing valuable clinical feedback for static tumor entities and shall be extended to monitor the treatment of intra-fractional moving tumors like in the lung or liver which are subjected to respiratory motion. The potential of 4D in-beam PET for the detection of possible malfunction of the motion compensated beam delivery has been investigated by means of systematic phantom experiments at the clinical in-beam PET installation at GSI Darmstadt. The new system for tracking moving targets with the scanned ion beam at GSI Darmstadt was used to adapt the Bragg peak positions laterally and in depth. The pencil beam has been rescanned on a horizontal line in a phantom placed at the central plane of the double head PET scanner with an energy corresponding to 60mm penetration depth while the target was performing a one dimensional periodic motion perpendicular to the beam direction. 4D PET data were compared with an appropriate 3D PET measurement which followed immediately after the dynamic acquisition. It is shown for different irradiation scenarios that in-beam PET is capable for detecting treatment errors for moving target irradiation.

Tumor therapy using particle beams is highly precise and requires methods for monitoring of dose delivery. Solutions based on positron emission tomography (PET) are successfully implemented for the radiation therapy with carbon ions and protons at the Gesellschaft für Schwerionenforschung, Darmstadt, Germany, at the Heavy Ion Medical Accelerator at Chiba, Japan, at the Massachusetts General Hospital, Boston, USA, at the Hyogo Ion Beam Medical Center, Japan as well as at the National Cancer Center Kashiwa, Japan. Furthermore, the PET monitoring technique has been tested experimentally for 3He, 7Li, and 16O. The main requirements for the PET monitoring are (1) to produce images containing relevant information for the evaluation of dose delivery and (2) to reduce the additional time required for imaging as much as possible. There are three technical realizations: (1) In-beam PET (measurement during the irradiation), (2) In-room PET (measurement immediately after the irradiation of each portal using a PET scanner placed in the therapy room), (3) Off-line PET (measurement after the complete irradiation by means of a PET scanner located in a different room). These three concepts have been evaluated concerning workflow, counting statistics, and imaging. The treatment workflow is mostly affected by off-line PET. In the case of in-room and off-line PET, the counting statistics is approximately one half of that for in-beam PET if reasonable measuring times (<= 15 min) are assumed. Furthermore, there is an information loss using off-line PET. Thus, in-beam and in-room PET are the most feasible concepts to integrate PET into the particle therapy for dose monitoring.

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At present, positron emission tomography (PET) is the only available technique for an in-vivo, non-invasive monitoring of the dose delivery precision in highly conformal ion beam therapy. The successful exploitation of in-beam PET at the Gesellschaft fuer Schwerionenforschung (GSI), Darmstadt, Germany during the last decade and a rising number of built or planned proton and heavier ion therapy facilities worldwide makes the development of a particle therapy PET (PT-PET) system of the next generation reasonable. The in-beam PET installation at GSI is a double-head positron scanner with a very limited solid angle which results in severe artifacts in the reconstructed images and in a low counting statistics. Thus, it is highly desirable to have larger solid angle coverage for PT-PET scanners of the next generation. However, increasing the effective area of a scanner might be limited by several requirements for the equipment of a radiotherapy treatment unit. Possible solutions for a prospective PT-PET system as well as a methodology for the evaluation of concurrent designs of the scanner taking into account the requirements of a therapy facility are discussed in this paper.

In-beam PET is a valuable method for a beam-delivery independent dose monitoring in radiation therapy with ion beams. The clinical feasibility of in-beam PET has been demonstrated for carbon and proton beams up to now. From radiobiological point of view it is highly desirable to perform tumor irradiation also with other ions. To extend the application of in-beam PET also to these ions, extensive knowledge about positron emitter production via nuclear fragmentation reactions during ion irradiation is necessary. To model the positron emitter production correctly, cross sections for all possible nuclear reactions occurring in the tissue during irradiation and leading to positron emitters are required. Since for many ions of therapeutic interest these cross sections are not available in the required energy range, a novel approach for estimating the positron emitter production from experimental data is introduced. The prediction of positron emitter distributions is based on depth dependent thick target yields, which are deduced by linear superposition of measured yields in water, graphite and polyethylene as reference materials. First results on the prediction of positron emitter distributions in polymethyl methacrylate (PMMA) targets induced by Li and C irradiation are presented. By comparison with data deduced from experiments, it is shown that a rather accurate prediction of positron emitter distribution in PMMA is possible with this method.

Ion beams offer the possibility of improved conformation of the dose delivered to the tumour with better sparing of surrounding tissue and critical structures in comparison to conventional photon and electron external radiation treatment modalities. Full clinical exploitation of this advantage can benefit from in-vivo confirmation of the actual beam delivery and, in particular, of the ion range in the patient. During irradiation, positron emitters like 15O (half-life T1/2 » 2 min) and 11C (T1/2 » 20 min) are formed in nuclear interactions between the ions and the tissue. Detection of this transient radioactivity via Positron Emission Tomography (PET) and comparison with the expectation based on the prescribed beam application may serve as an in-vivo, non-invasive range validation method of the whole treatment planning and delivery chain. For technical implementation, PET imaging during irradiation (in-beam) requires the development of customized, limited angle detectors with data acquisition synchronized with the beam delivery. Alternatively, commercial PET or PET/CT scanners in close proximity to the treatment site enable detection of the residual activation from long-lived emitters shortly after treatment (offline). This paper reviews two clinical examples using a dedicated in-beam PET scanner for verification of carbon ion therapy at GSI Darmstadt, Germany, as well as a commercial offline PET/CT tomograph for post-radiation imaging of proton treatments at Massachusetts General Hospital, Boston, USA. Challenges as well as pros and cons of the two imaging approaches in dependence of the different ion type and beam delivery system are discussed.

Due to the special characteristics of ion beams and delicate treatment situations, i.e. in close vicinity to organs at risk, a three-dimensional, in-vivo and in-situ monitoring of the dose delivery is highly desirable. At present, in-beam PET is the only method meeting these requirements. An in-beam PET system has been implemented for clinical application at the carbon ion therapy facility of the Gesellschaft für Schwerionenforschung (GSI) Darmstadt. So far, more than 400 patients have been monitored with this system. It could be demonstrated that this PET technique is capable of assessing relevant parameters for quality assurance of carbon ion therapy, measuring the particle range in tissue, the position of the irradiated volume with respect to anatomical landmarks, and estimating local deviations between the planned and applied dose. In-beam PET has become a tool providing valuable clinical feedback. The implementation of the in-beam PET system at the medical beamline at GSI will be described. Clinical results will be shown with examples. Furthermore, the application of in-beam PET for protons, 3-He, 7-Li and 16-O shows promising results and will be presented.