Final Report Summary - APCT (Antiproton Beams for Cancer Therapy)
In accordance with the initial research plan a concerted research effort to establish a base data set for potential future use of antiprotons in cancer therapy of specific and hard to treat cancer cases was conducted. To have clinical relevance a new extraction scheme to extract 126 MeV antiprotons from the Antiproton Decelerator (AD) at CERN has been developed in close collaboration with the accelerator operations team at CERN. This beam has a penetration depth of about 11 cm in human tissue-like targets. Using an automatic degrader wheel the beam was used to provide a spread-out Bragg peak (SOBP) of approximately 15 mm depth, suitable to potentially treat small tumors.
During the project period 3 beam times were provided by the AD, each of approximately 1 week duration, in which irradiation experiments on V-79 Chinese Hamster cells embedded in a gelatin matrix were conducted. In addition, developmental work on dosimetry of high Linear Energy Transfer (LET) particles was carried out.
High LET particles can inflict significant damage to the DNA in a single hit, and such beams (e.g. Carbon ions, Oxygen ions, and Antiprotons) are expected to have an increased biological efficiency (RBE) in treating radio-resistant tumors. Additionally, work was performed on novel beam monitors for hadron therapy, on direct LET measurement devices, and on real-time imaging of the applied dose distribution.
In parallel, a number of experiments with photons were conducted at the University of Aarhus, the DKFZ, and with Carbon ions at GSI and the HIT facility.
Compared to proton beams antiprotons exhibit a two times higher Bragg peak due to the annihilation energy deposited locally. In addition, antiprotons exhibit a photon-like RBE at the entrance to the target, which then sharply increases at the beginning of the SOBP to about 1.7 - 2.0. This sharply contrasts the slow increase of RBE along the beam path of Carbon ions, and complements the increase of physical dose in the Bragg peak of antiprotons.
Virtual planning studies that were carried out in the frame of this project on a 4x4x4 cm size target visualized this advantage. Comparing protons, antiprotons, and carbon ions, it is now obvious that antiprotons have the lowest dose in the entrance channel and that they show a spherical dose halo surrounding the Bragg peak region. These preliminary data will have to be corrected for the RBE data obtained in the project and can then be applied to virtual planning studies on actual patient data. Promising candidates are small sizes tumors (< 10 cm3) attached to critical structures such as for example the brain stem or spinal cord, and tumors that can only be treated using primary beam paths through regions of sensitive tissue or which have been irradiated in prior treatments.
Much of the work at this stage is Monte Carlo-driven and important benchmarking studies were conducted. Thereby, several inconsistencies in the predictions offered by FLUKA, which nowadays is widely used for Monte Carlo calculations in clinical settings, were found. These issues are presently being resolved in collaboration with the FLUKA developers. Thereby the results of this study will show benefits well beyond the initial project and also impact positively on the research activities of a large number of other research teams applying FLUKA in the low energy regime.
Throughout the funding period, the project has been highly interdisciplinary and required input and consultation from many different fields. The original AD-4/ACE collaboration has been considerably broadened, including now several European institutions, thus contributing to an active bi-directional knowledge exchange.
Dissemination of all results was ensured through a number of publications, the organization of, and participation in, international workshops and conferences. Thereby an active discussion on general issues in hadron therapy has been ignited, involving institutions from Europe and the US.
During the project period 3 beam times were provided by the AD, each of approximately 1 week duration, in which irradiation experiments on V-79 Chinese Hamster cells embedded in a gelatin matrix were conducted. In addition, developmental work on dosimetry of high Linear Energy Transfer (LET) particles was carried out.
High LET particles can inflict significant damage to the DNA in a single hit, and such beams (e.g. Carbon ions, Oxygen ions, and Antiprotons) are expected to have an increased biological efficiency (RBE) in treating radio-resistant tumors. Additionally, work was performed on novel beam monitors for hadron therapy, on direct LET measurement devices, and on real-time imaging of the applied dose distribution.
In parallel, a number of experiments with photons were conducted at the University of Aarhus, the DKFZ, and with Carbon ions at GSI and the HIT facility.
Compared to proton beams antiprotons exhibit a two times higher Bragg peak due to the annihilation energy deposited locally. In addition, antiprotons exhibit a photon-like RBE at the entrance to the target, which then sharply increases at the beginning of the SOBP to about 1.7 - 2.0. This sharply contrasts the slow increase of RBE along the beam path of Carbon ions, and complements the increase of physical dose in the Bragg peak of antiprotons.
Virtual planning studies that were carried out in the frame of this project on a 4x4x4 cm size target visualized this advantage. Comparing protons, antiprotons, and carbon ions, it is now obvious that antiprotons have the lowest dose in the entrance channel and that they show a spherical dose halo surrounding the Bragg peak region. These preliminary data will have to be corrected for the RBE data obtained in the project and can then be applied to virtual planning studies on actual patient data. Promising candidates are small sizes tumors (< 10 cm3) attached to critical structures such as for example the brain stem or spinal cord, and tumors that can only be treated using primary beam paths through regions of sensitive tissue or which have been irradiated in prior treatments.
Much of the work at this stage is Monte Carlo-driven and important benchmarking studies were conducted. Thereby, several inconsistencies in the predictions offered by FLUKA, which nowadays is widely used for Monte Carlo calculations in clinical settings, were found. These issues are presently being resolved in collaboration with the FLUKA developers. Thereby the results of this study will show benefits well beyond the initial project and also impact positively on the research activities of a large number of other research teams applying FLUKA in the low energy regime.
Throughout the funding period, the project has been highly interdisciplinary and required input and consultation from many different fields. The original AD-4/ACE collaboration has been considerably broadened, including now several European institutions, thus contributing to an active bi-directional knowledge exchange.
Dissemination of all results was ensured through a number of publications, the organization of, and participation in, international workshops and conferences. Thereby an active discussion on general issues in hadron therapy has been ignited, involving institutions from Europe and the US.