Michael Scholz

Bio: Michael Scholz is an academic researcher from GSI Helmholtz Centre for Heavy Ion Research. The author has contributed to research in topics: Relative biological effectiveness & Sobp. The author has an hindex of 29, co-authored 92 publications receiving 2394 citations.

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

Abstract: 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...

Biophysical calculation of cell survival probabilities using amorphous track structure models for heavy-ion irradiation.

Abstract: Both the microdosimetric kinetic model (MKM) and the local effect model (LEM) can be used to calculate the surviving fraction of cells irradiated by high-energy ion beams. In this study, amorphous track structure models instead of the stochastic energy deposition are used for the MKM calculation, and it is found that the MKM calculation is useful for predicting the survival curves of the mammalian cells in vitro for (3)He-, (12)C- and (20)Ne-ion beams. The survival curves are also calculated by two different implementations of the LEM, which inherently used an amorphous track structure model. The results calculated in this manner show good agreement with the experimental results especially for the modified LEM. These results are compared to those calculated by the MKM. Comparison of the two models reveals that both models require three basic constituents: target geometry, photon survival curve and track structure, although the implementation of each model is significantly different. In the context of the amorphous track structure model, the difference between the MKM and LEM is primarily the result of different approaches calculating the biological effects of the extremely high local dose in the center of the ion track.

LET, track structure and models. A review.

Abstract: Swift heavy ions when penetrating through matter strip off those electrons having a smaller orbital velocity than the ion velocity. The remaining electrons screen the nuclear charge yielding an effective charge. The effective charge of the ions interacts predominantly with the target electrons causing excitation and ionizations of the target atoms. Using the Bethe Bloch formula for the energy loss combined with the Barkas formula for effective charge, the energy loss values as well as unrestricted and restricted linear transfer can be calculated within a few percent of accuracy. From the primary energy loss only a small fraction of 10% or less is transformed into excitation. The major part of the energy loss is used for the ionization of the target atoms and the emission of the corresponding electrons with a high kinetic energy. These electrons form the track around the trajectory of the primary ion in which two thirds of the primary energy is deposited by collisions of primary, secondary and later generations of electrons with the target molecules. In the electron diffusion process the energy is transported from the center of the track into the halo. The radial dose decreases with the square of the radial distance from the center. The diameter of the track is determined by the maximum range of the emitted electrons, i.e. by the maximum energy electrons. All ions having the same velocity i.e. the same specific energy produce electrons of the same energy and therefore tracks of the same diameters independent of the effective charge. But the dose inside the track increases with the square of the effective charge. Track structure models using this continuous dose distributions produce a better agreement with the experiment than models based on microdosimetry. The critical volume as used in microdosimetry is too large compared to the size of the DNA as critical structure inside the biological objects. Track structure models yield better results because the gross-structure of the track i.e. its lateral extension and the thin down toward the end of the track is included in these calculations. In a recent refinement the repair capacity of the cell has been included in a track structure model by using the complete shouldered x-ray survival curve as a template for the local damage produced by the particle tracks. This improved model yields presently the best agreement with the experiment.

The FLUKA Monte Carlo code coupled with the local effect model for biological calculations in carbon ion therapy

Abstract: Clinical Monte Carlo (MC) calculations for carbon ion therapy have to provide absorbed and RBE-weighted dose. The latter is defined as the product of the dose and the relative biological effectiveness (RBE). At the GSI Helmholtzzentrum fur Schwerionenforschung as well as at the Heidelberg Ion Therapy Center (HIT), the RBE values are calculated according to the local effect model (LEM). In this paper, we describe the approach followed for coupling the FLUKA MC code with the LEM and its application to dose and RBE-weighted dose calculations for a superimposition of two opposed (12)C ion fields as applied in therapeutic irradiations. The obtained results are compared with the available experimental data of CHO (Chinese hamster ovary) cell survival and the outcomes of the GSI analytical treatment planning code TRiP98. Some discrepancies have been observed between the analytical and MC calculations of absorbed physical dose profiles, which can be explained by the differences between the laterally integrated depth-dose distributions in water used as input basic data in TRiP98 and the FLUKA recalculated ones. On the other hand, taking into account the differences in the physical beam modeling, the FLUKA-based biological calculations of the CHO cell survival profiles are found in good agreement with the experimental data as well with the TRiP98 predictions. The developed approach that combines the MC transport/interaction capability with the same biological model as in the treatment planning system (TPS) will be used at HIT to support validation/improvement of both dose and RBE-weighted dose calculations performed by the analytical TPS.

Carbon ion radiotherapy for chordomas and low-grade chondrosarcomas of the skull base. Results in 67 patients.

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 fur 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°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.

Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer

Abstract: Proton therapy treatments are based on a proton RBE (relative biological effectiveness) relative to high-energy photons of 1.1. The use of this generic, spatially invariant RBE within tumors and normal tissues disregards the evidence that proton RBE varies with linear energy transfer (LET), physiological and biological factors, and clinical endpoint.Based on the available experimental data from published literature, this review analyzes relationships of RBE with dose, biological endpoint and physical properties of proton beams. The review distinguishes between endpoints relevant for tumor control probability and those potentially relevant for normal tissue complication. Numerous endpoints and experiments on sub-cellular damage and repair effects are discussed.Despite the large amount of data, considerable uncertainties in proton RBE values remain. As an average RBE for cell survival in the center of a typical spread-out Bragg peak (SOBP), the data support a value of ~1.15 at 2 Gy/fraction. The proton RBE increases with increasing LETd and thus with depth in an SOBP from ~1.1 in the entrance region, to ~1.15 in the center, ~1.35 at the distal edge and ~1.7 in the distal fall-off (when averaged over all cell lines, which may not be clinically representative). For small modulation widths the values could be increased. Furthermore, there is a trend of an increase in RBE as (α/β)x decreases. In most cases the RBE also increases with decreasing dose, specifically for systems with low (α/β)x. Data on RBE for endpoints other than clonogenic cell survival are too diverse to allow general statements other than that the RBE is, on average, in line with a value of ~1.1.This review can serve as a source for defining input parameters for applying or refining biophysical models and to identify endpoints where additional radiobiological data are needed in order to reduce the uncertainties to clinically acceptable levels.

Heavy-ion tumor therapy: Physical and radiobiological benefits

Abstract: 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

Charged particles in radiation oncology

Abstract: 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.

Radiation oncology in the era of precision medicine

Abstract: Technological advances and clinical research over the past few decades have given radiation oncologists the capability to personalize treatments for accurate delivery of radiation dose based on clinical parameters and anatomical information. Eradication of gross and microscopic tumours with preservation of health-related quality of life can be achieved in many patients. Two major strategies, acting synergistically, will enable further widening of the therapeutic window of radiation oncology in the era of precision medicine: technology-driven improvement of treatment conformity, including advanced image guidance and particle therapy, and novel biological concepts for personalized treatment, including biomarker-guided prescription, combined treatment modalities and adaptation of treatment during its course.