Michael H. Holzscheiter

Comparison of optimized single and multifield irradiation plans of antiproton, proton and carbon ion beams.

BACKGROUND AND PURPOSEnAntiprotons have been suggested as a possibly superior modality for radiotherapy, due to the energy released when antiprotons annihilate, which enhances the Bragg peak and introduces a high-LET component to the dose. However, concerns are expressed about the inferior lateral dose distribution caused by the annihilation products.nnnMETHODSnWe use the Monte Carlo code FLUKA to generate depth-dose kernels for protons, antiprotons, and carbon ions. Using these we then build virtual treatment plans optimized according to ICRU recommendations for the different beam modalities, which then are recalculated with FLUKA. Dose-volume histograms generated from these plans can be used to compare the different irradiations.nnnRESULTSnThe enhancement in physical and possibly biological dose from annihilating antiprotons can significantly lower the dose in the entrance channel; but only at the expense of a diffuse low dose background from long-range secondary particles. Lateral dose distributions are improved using active beam delivery methods, instead of flat fields.nnnCONCLUSIONSnDose-volume histograms for different treatment scenarios show that antiprotons have the potential to reduce the volume of normal tissue receiving medium to high dose, however, in the low dose region antiprotons are inferior to both protons and carbon ions. This limits the potential usage to situations where dose to normal tissue must be reduced as much as possible.

The antiproton depth–dose curve in water

We have measured the depth-dose curve of 126 MeV antiprotons in a water phantom using ionization chambers. Since the antiproton beam provided by CERN has a pulsed structure and possibly carries a high-LET component from the antiproton annihilation, it is necessary to correct the acquired charge for ion recombination effects. The results are compared with Monte Carlo calculations and were found to be in good agreement. Based on this agreement we calculate the antiproton depth-dose curve for antiprotons and compare it with that for protons and find a doubling of the physical dose in the peak region for antiprotons.

A community call for a dedicated radiobiological research facility to support particle beam cancer therapy

Recently more than one hundred researchers followed an invitation to a brainstorming meeting at CERN on the topic of a future dedicated radio-biological and radio-physical research center. Many more joined the meeting via webcast. After a day of presentations and discussions it was clear, that an urgent need for such a development exists, resulting in a community call for the construction of a dedicated laboratory. Below we comment on the essential points.

Antiproton induced DNA damage: proton like in flight, carbon-ion like near rest

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (~19u2005keV/μm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual γ-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ~1.48 in the SOBP and ~1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28–42u2005mm away from the primary beam suggesting minimal risk from long-range secondary particles.

Dose calculation in biological samples in a mixed neutron-gamma field at the TRIGA reactor of the University of Mainz

Abstract To establish Boron Neutron Capture Therapy (BNCT) for non-resectable liver metastases and for in vitro experiments at the TRIGA Mark II reactor at the University of Mainz, Germany, it is necessary to have a reliable dose monitoring system. The in vitro experiments are used to determine the relative biological effectiveness (RBE) of liver and cancer cells in our mixed neutron and gamma field. We work with alanine detectors in combination with Monte Carlo simulations, where we can measure and characterize the dose. To verify our calculations we perform neutron flux measurements using gold foil activation and pin-diodes. Material and methods. When L-α-alanine is irradiated with ionizing radiation, it forms a stable radical which can be detected by electron spin resonance (ESR) spectroscopy. The value of the ESR signal correlates to the amount of absorbed dose. The dose for each pellet is calculated using FLUKA, a multipurpose Monte Carlo transport code. The pin-diode is augmented by a lithium fluoride foil. This foil converts the neutrons into alpha and tritium particles which are products of the 7Li(n,α)3H-reaction. These particles are detected by the diode and their amount correlates to the neutron fluence directly. Results and discussion. Gold foil activation and the pin-diode are reliable fluence measurement systems for the TRIGA reactor, Mainz. Alanine dosimetry of the photon field and charged particle field from secondary reactions can in principle be carried out in combination with MC-calculations for mixed radiation fields and the Hansen & Olsen alanine detector response model. With the acquired data about the background dose and charged particle spectrum, and with the acquired information of the neutron flux, we are capable of calculating the dose to the tissue. Conclusion. Monte Carlo simulation of the mixed neutron and gamma field of the TRIGA Mainz is possible in order to characterize the neutron behavior in the thermal column. Currently we also speculate on sensitizing alanine to thermal neutrons by adding boron compounds.

Calculated LET spectrum from antiproton beams stopping in water

Introduction. Antiprotons have been proposed as a potential modality for radiotherapy because the annihilation at the end of range leads to roughly a doubling of physical dose in the Bragg peak region. So far it has been anticipated that the radiobiology of antiproton beams is similar to that of protons in the entry region of the beam, but very different in the annihilation region, due to the expected high-LET components resulting from the annihilation. On closer inspection we find that calculations of dose averaged LET in the entry region may suggest that the RBE of antiprotons in the plateau region could significantly differ from unity, which seems to warrant closer inspection of the radiobiology in this region. Materials and Methods. Monte Carlo simulations using FLUKA were performed for calculating the entire particle spectrum of a beam of 126 MeV antiprotons hitting a water phantom. Results and Discussion. In the plateau region of the simulated antiproton beam we observe a dose-averaged unrestricted LET of about 4 keV/µm, which is very different from the expected 0.6 keV/µm of an equivalent primary proton beam. Even though the fluence of secondaries is a magnitude less than the fluence of primary particles, the increased stopping power of the secondary particles causes an increase in the dose averaged LET which is expected to result in a RBE different from unity.

Real-time imaging for dose evaluation during antiproton irradiation

Online monitoring of the stopping distribution of particle beams used for radiotherapy provides the possibility of detecting possible errors in dose deposition early during a given treatment session, and may therefore help to improve the quality of the therapy. Antiproton annihilation events produce several long-range secondary particles which can be detected in real time by standard high energy particle physics detector systems. In this note, Monte Carlo calculations are performed in order to study the feasibility of real-time imaging by detecting charged pions produced during antiproton irradiation of typical biological targets. A simple treatment plan in a water phantom is simulated and the results show that by detecting pi+/- the position and the size of the planned target volume can be located with precision in the order of 1 mm.

Cancer therapy with antiprotons

Starting in 2003 the AD‐4/ACE collaboration has studied the biological effects of antiprotons annihilating in a human tissue like material on live V‐79 Chinese Hamster cells. The main goal of the work is to prove the efficacy of antiprotons for cancer therapy. In this report we discuss a critical point to be considered carefully for all particle beam radiation therapies, namely the loss of primary particles from the beam on the way to a tumor seated some distance below the surface.

Neutron Fluence in Antiproton Radiotherapy, Measurements and Simulations

Abstract Introduction: A significant part of the secondary particle spectrum from antiproton annihilation consists of fast neutrons, which may contribute to a significant dose background found outside the primary beam. Materials and Methods: Using a polystyrene phantom as a moderator, we have performed absolute fluence measurements of the thermalized part of the fast neutron spectrum using Lithium-6 and −7 Fluoride TLD pairs. The results were compared with the Monte Carlo particle transport code FLUKA. Results: The experimental results are found to be in good agreement with simulations. The thermal neutron kerma resulting from the measured thermal neutron fluence is insignificant compared to the contribution from fast neutrons. Discussion: The secondary neutron fluences encountered in antiproton therapy are found to be similar to values calculated for pion treatment, however exact modeling under more realistic treatment scenarios is still required to quantitatively compare these treatment modalities.

V-79 Chinese Hamster cells irradiated with antiprotons, a study of peripheral damage due to medium and long range components of the annihilation radiation

Purpose:u2003Radiotherapy of cancer carries a perceived risk of inducing secondary cancer and other damage due to dose delivered to normal tissue. While expectedly small, this risk must be carefully analysed for all modalities. Especially in the use of exotic particles like pions and antiprotons, which annihilate and produce a mixed radiation field when interacting with normal matter nuclei, the biological effective dose far out of field needs to be considered in evaluating this approach. We describe first biological measurements to address the concern that medium and long range annihilation products may produce a significant background dose and reverse any benefits of higher biological dose in the target area. Materials and methods:u2003Using the Antiproton Decelerator (AD) at CERN (Conseil Européen pour la Recherche Nucléaire) we irradiated V-79 Chinese Hamster cells embedded in gelatine using an antiproton beam with fluence ranging from 4.5u2009×u2009108 to 4.5u2009×u2009109 particles, and evaluated the biological effect on cells located distal to the Bragg peak using clonogenic survival and the COMET assay. Results:u2003Both methods show a substantial biological effect on the cells in the entrance channel and the Bragg Peak area, but any damage is reduced to levels well below the effect in the entrance channel 15u2009mm distal to the Bragg peak for even the highest particle fluence used. Conclusions:u2003The annihilation radiation generated by antiprotons stopping in biological targets causes an increase of the penumbra of the beam but the effect rapidly decreases with distance from the target volume. No major increase in the biological effect is found in the far field outside of the primary beam.