High-energy beams of charged nuclear particles (protons and heavier ions) offer significant advantages for the treatment of deep-seated local tumors in comparison to conventional megavolt photon therapy. Their physical depth-dose distribution in tissue is characterized by a small entrance dose and a distinct maximum (Bragg peak) near the end of range with a sharp fall-off at the distal edge. Taking full advantage of the well-defined range and the small lateral beam spread, modern scanning beam systems allow delivery of the dose with millimeter precision. In addition, projectiles heavier than protons such as carbon ions exhibit an enhanced biological effectiveness in the Bragg peak region caused by the dense ionization of individual particle tracks resulting in reduced cellular repair. This makes them particularly attractive for the treatment of radio-resistant tumors localized near organs at risk. While tumor therapy with protons is a well-established treatment modality with more than 60 000 patients treated worldwide, the application of heavy ions is so far restricted to a few facilities only. Nevertheless, results of clinical phase I-II trials provide evidence that carbon-ion radiotherapy might be beneficial in several tumor entities. This article reviews the progress in heavy-ion therapy, including physical and technical developments, radiobiological studiesmore » and models, as well as radiooncological studies. As a result of the promising clinical results obtained with carbon-ion beams in the past ten years at the Heavy Ion Medical Accelerator facility (Japan) and in a pilot project at GSI Darmstadt (Germany), the plans for new clinical centers for heavy-ion or combined proton and heavy-ion therapy have recently received a substantial boost.« less

Heavy-ion tumor therapy: Physical and radiobiological benefits

Radiotherapy is one of the most common and effective therapies for cancer. Generally, patients are treated with X-rays produced by electron accelerators. Many years ago, researchers proposed that high-energy charged particles could be used for this purpose, owing to their physical and radiobiological advantages compared with X-rays. Particle therapy is an emerging technique in radiotherapy. Protons and carbon ions have been used for treating many different solid cancers, and several new centers with large accelerators are under construction. Debate continues on the cost:benefit ratio of this technique, that is, on whether the high costs of accelerators and beam delivery in particle therapy are justified by a clear clinical advantage. This Review considers the present clinical results in the field, and identifies and discusses the research questions that have resulted with this technique.

Charged particles in radiation oncology

We describe a novel approach to treatment planning for heavy-ion radiotherapy based on the local effect model (LEM) which allows us to calculate the biologically effective dose not only for the target region but also for the entire irradiation volume. LEM is ideally suited for use as an integral part of treatment planning code systems for active dose shaping devices like the GSI raster scan system. Thus it has been incorporated into our standard treatment planning system for ion therapy (TRiP). Single intensity modulated fields can be optimized with respect to a homogeneous biologically effective dose. The relative biological effectiveness (RBE) is calculated separately for each voxel of the patient CT. Our radiobiologically oriented code system has been used since 1995 for the planning of irradiation experiments with cell cultures and animals such as rats and minipigs. It has been in regular and successful use for patient treatment planning since 1997.

https://iopscience.iop.org/article/10.1088/0031-9155/45/11/314/pdf

Treatment planning for heavy-ion radiotherapy: calculation and optimization of biologically effective dose.

Tumor therapy with heavy charged particles

Purpose: To present the first direct experimental in vitro comparison of the biological effectiveness of rangeequivalent protons and carbon ion beams for Chinese hamsterovary cells exposed in a three-dimensional phantom using a pencil beam scanning technique and to compare the experimental data with a novel biophysical model. Methodsand Materials:Cell survivalwasmeasuredinthe phantomafter irradiation withtwo opposingfields,thus mimicking the typical patient treatment scenario. The novel biophysical model represents a substantial extension of the local effect model, previously used for treatment planning in carbon ion therapy for more than 400 patients, and potentially can be used to predict effectiveness of all ion species relevant for radiotherapy. A key feature of the new approach is the more sophisticated consideration of spatially correlated damage induced by ion irradiation. Results: The experimental data obtained for Chinese hamster ovary cells clearly demonstrate that higher cell killing is achieved in the target region with carbon ions as compared with protons when the effects in the entrance channel are comparable. The model predictions demonstrate agreement with these experimental data and with data obtained with helium ions under similar conditions. Good agreement is also achieved with relative biological effectiveness values reported in the literature for other cell lines for monoenergetic proton, helium, and carbon ions. Conclusion: Both the experimental data and the new modeling approach are supportive of the advantages of carbon ions as compared with protons for treatment-like field configurations. Because the model predicts the effectiveness for several ion species with similar accuracy, it represents a powerful tool for further optimization and utilization of the potential of ion beams in tumor therapy. 2010 Elsevier Inc. Ion beam therapy, Relative biological effectiveness (RBE), Biophysical model, Treatment planning.

Quantification of the Relative Biological Effectiveness for Ion Beam Radiotherapy: Direct Experimental Comparison of Proton and Carbon Ion Beams and a Novel Approach for Treatment Planning

Purpose: The LET position of the RBE maximum and its dependence on the cellular repair capacity was determined for carbon ions. Hamster celllines of differing repair capacity were irradiated with monoenergetic carbon ions. RBE values for cell inactivation at different survival levels were determined and the differences in the RBE-LET patterns were compared with the individual sensitivity to photon irradiation of the different cell lines. Material and methods: Three hamster cell lines, the wild-type cell lines V79 and CHO-K1 and the radiosensitive CHO mutant xrs5, were irradiated with carbon ions of different energies (2.4-266.4MeV/u) and LET values (13.7-482.7keV/mum) and inactivation data were measured in comparison to 250kV x-rays. Results: For the repair-proficient cell lines a RBE maximum was found at LET values between 150 and 200keV/mum. For the repair-deficient cell line the RBE failed to show a maximum and decreased continuously for LET values above 100keV/mum. Conclusions: The carbon RBE-LET rela...

RBE for carbon track-segment irradiation in cell lines of differing repair capacity

Purpose : To investigate the radiation-induced, premature terminal differentiation and collagen production of fibroblasts after heavy ion irradiation. These endpoints are discussed as an underlying cellular mechanism of fibrosis. Materials and methods : Normal human foreskin fibroblasts (AG1522B) were used to determine clonogenic survival, the premature differentiation and synthesis of extracellular matrix (ECM) proteins, e.g. collagen after irradiation with X-rays, 195 and 11.0 MeV u -1 carbon ions and 9.9 MeV u -1 nickel ions. Additionally, biopsies from the skin of minipigs were taken. Similar experiments were carried out after irradiation with X-rays and 195 MeV u -1 carbon ions. Results and conclusions : RBE for clonogenic survival as well as for fibrosis-related parameters for high-energy carbon ions are slightly above unity. Low-energy carbon ions with a higher LET are more efficient than X-rays, whereas the RBE of nickel ions is below unity. The results obtained for the differentiation pattern and...

W. K. Weyrather

Papers

RBE for carbon track-segment irradiation in cell lines of differing repair capacity

Changes of fibrosis-related parameters after high- and low-LET irradiation of fibroblasts