Purpose: We report on the development of the open-source cross-platform radiation treatment planning toolkit matRad and its comparison against validated treatment planning systems. The toolkit enables three-dimensional intensity-modulated radiation therapy treatment planning for photons, scanned protons and scanned carbon ions. Methods: matRad is entirely written in Matlab and is freely available online. It re-implements wellestablished algorithms employing a modular and sequential software design to model the entire treatment planning workflow. It comprises core functionalities to import DICOM data, to calculate and optimize dose as well as a graphical user interface for visualization. matRad dose calculation algorithms (for carbon ions this also includes the computation of the relative biological effect) are compared against dose calculation results originating from clinically approved treatment planning systems. Results: We observe three-dimensional c-analysis pass rates ≥ 99.67% for all three radiation modalities utilizing a distance to agreement of 2 mm and a dose difference criterion of 2%. The computational efficiency of matRad is evaluated in a treatment planning study considering three different treatment scenarios for every radiation modality. For photons, we measure total run times of 145 s-1260 s for dose calculation and fluence optimization combined considering 4-72 beam orientations and 2608-13597 beamlets. For charged particles, we measure total run times of 63 s-993 s for dose calculation and fluence optimization combined considering 9963-45574 pencil beams. Using a CT and dose grid resolution of 0.3 cm 3 requires a memory consumption of 1.59 GB-9.07 GB and 0.29 GB-17.94 GB for photons and charged particles, respectively. Conclusion: The dosimetric accuracy, computational performance and open-source character of matRad encourages a future application of matRad for both educational and research purposes.

Monte Carlo (MC) simulations of beam interaction and transport in matter are increasingly considered as essential tools to support several aspects of radiation therapy. Despite the vast application of MC to photon therapy and scattered proton therapy, clinical experience in scanned ion beam therapy is still scarce. This is especially the case for ions heavier than protons, which pose additional issues like nuclear fragmentation and varying biological effectiveness. In this work, we present the evaluation of a dedicated framework which has been developed at the Heidelberg Ion Beam Therapy Center to provide automated FLUKA MC simulations of clinical patient treatments with scanned proton and carbon ion beams. Investigations on the number of transported primaries and the dimension of the geometry and scoring grids have been performed for a representative class of patient cases in order to provide recommendations on the simulation settings, showing that recommendations derived from the experience in proton therapy cannot be directly translated to the case of carbon ion beams. The MC results with the optimized settings have been compared to the calculations of the analytical treatment planning system (TPS), showing that regardless of the consistency of the two systems (in terms of beam model in water and range calculation in different materials) relevant differences can be found in dosimetric quantities and range, especially in the case of heterogeneous and deep seated treatment sites depending on the ion beam species and energies, homogeneity of the traversed tissue and size of the treated volume. The analysis of typical TPS speed-up approximations highlighted effects which deserve accurate treatment, in contrast to adequate beam model simplifications for scanned ion beam therapy. In terms of biological dose calculations, the investigation of the mixed field components in realistic anatomical situations confirmed the findings of previous groups so far reported only in homogenous water targets. This work can thus be useful to other centers commencing clinical experience in scanned ion beam therapy.

Modern radiotherapy (RT) techniques are widely used in the irradiation of moving organs. A crucial step in ensuring the correct position of a target structure directly before or during treatment is daily image guidance by computed tomography (CT) or X-ray radiography (image-guided radiotherapy, IGRT). Therefore, combinations of modern irradiation devices and imaging, such as on-board imaging (OBI) with X-rays, or in-room CT such as the tomotherapy system, have been developed. Moreover, combinations of linear accelerators and in-room CT-scanners have been designed. IGRT is of special interest in hypofractionated and radiosurgical treatments where high single doses are applied in the proximity of critical organs at risk. Radiographically visible markers in or in close proximity to the target structure may help to reproduce the position during RT and could therefore be used as external surrogates for motion monitoring. Criteria sought for fiducial markers are (i) visibility in the radiologic modalities involved in radiotherapeutic treatment planning and image guidance, such as CT and kilovoltage (kV) OBI), (ii) low production of imaging artifacts, and (iii) low perturbation of the therapeutic dose to the target volume. Photon interaction with interstitial markers has been shown to be not as important as in particle therapy, where interaction of the particle beam, especially with metal markers, can have a significant impact on treatment. This applies especially with a scanned ion beam. Recently we commenced patient recruitment at our institution within the PROMETHEUS trial, which evaluates a hypofractionation regime, starting with 4 x 10 Gy (RBE), for patients with hepatocellular carcinoma. The aim of this work is, therefore, to evaluate potential implantable fiducial markers for enabling precise patient and thus organ positioning in scanned ion beams. To transfer existing knowledge of marker application from photon to particle therapy, we used a range of commercially available markers of different forms and sizes, consisting of carbon and gold materials, and evaluated them for their potential use in the clinical setup with scanned ion beams at our institution. All markers were implanted in a standardized Alderson phantom and were examined using CT scans and orthogonal kV OBI in our clinical routine protocol. Impact on beam perturbation downstream of the markers in the plateau region of a spread-out Bragg peak (SOBP) was estimated by using radiographic films for clinical proton and carbon ion beams of high and low energies. All tested markers achieved good visibility in CT and kV OBI. Disturbances due to artifacts and dose perturbation were highest in the arbitrarily folded gold and the thickest gold marker, but especially low in the carbon marker. Dose perturbation was highest in the arbitrarily folded gold marker. In summary, the analyzed markers offer promising potential for identifying target structures in our treatment setup at HIT and will soon be used in clinical routine. However, a careful choice of marker, d...

BackgroundTo report on establishment of workflow and clinical results of particle therapy at the Heidelberg Ion Therapy Center.Materials and methodsWe treated 36 pediatric patients (aged 21 or younger) with particle therapy at HIT. Median age was 12 years (range 2-21 years), five patients (14%) were younger than 5 years of age. Indications included pilocytic astrocytoma, parameningeal and orbital rhabdomyosarcoma, skull base and cervical chordoma, osteosarcoma and adenoid-cystic carcinoma (ACC), as well as one patient with an angiofibroma of the nasopharynx. For the treatment of small children, an anesthesia unit at HIT was established in cooperation with the Department of Anesthesiology.ResultsTreatment concepts depended on tumor type, staging, age of the patient, as well as availability of specific study protocols. In all patients, particle radiotherapy was well tolerated and no interruptions due to toxicity had to be undertaken. During follow-up, only mild toxicites were observed. Only one patient died of tumor progression: Carbon ion radiotherapy was performed as an individual treatment approach in a child with a skull base recurrence of the previously irradiated rhabdomyosarcoma. Besides this patient, tumor recurrence was observed in two additional patients.ConclusionClinical protocols have been generated to evaluate the real potential of particle therapy, also with respect to carbon ions in distinct pediatric patient populations. The strong cooperation between the pediatric department and the department of radiation oncology enable an interdisciplinary treatment and stream-lined workflow and acceptance of the treatment for the patients and their parents.