Moderator of 2 Sessions
Presenter of 1 Presentation
Protons and Carbon Ions
Abstract
Abstract Body
Charged particles are to achieve the high dose-rates needed in FLASH radiotherapy, because the photon yield from bremsstrahlung has low efficacy. First results were indeed obtained with electrons, but soon it was shown that cyclotrons used in proton therapy could reach intensities high enough to allow treatments in FLASH regime, at least in 2D. A conformal 3D-FLASH treatment can be performed using 3D-printed range modulators. For heavier ions, synchrotrons are used to accelerate the nuclei to the high energies needed for therapy, and here FLASH dose rate conditions are more difficult to reach than for cyclotrons. We have recently shown that with proper beam adjustment it is possible to get >5·108 12C-ions in pulses <200 ms, thus enabling FLASH treatments with carbon ions. The use of carbon or heavier ions is interesting for two reasons. First, whether the FLASH sparing effect in normal tissue is also observed at high-LET is very important to understand the physico-chemical mechanisms of the FLASH effect. Second, heavy ion therapy is limited by toxicity in the entrance channel, which may be reduced at ultra-high dose rates. Here we will present the most recent in vitro and in vivo experiments performed at HIT and GSI synchrotrons with ultra-high intensities of 12C-ions.Author Of 5 Presentations
Protons and Carbon Ions
Abstract
Abstract Body
Charged particles are to achieve the high dose-rates needed in FLASH radiotherapy, because the photon yield from bremsstrahlung has low efficacy. First results were indeed obtained with electrons, but soon it was shown that cyclotrons used in proton therapy could reach intensities high enough to allow treatments in FLASH regime, at least in 2D. A conformal 3D-FLASH treatment can be performed using 3D-printed range modulators. For heavier ions, synchrotrons are used to accelerate the nuclei to the high energies needed for therapy, and here FLASH dose rate conditions are more difficult to reach than for cyclotrons. We have recently shown that with proper beam adjustment it is possible to get >5·108 12C-ions in pulses <200 ms, thus enabling FLASH treatments with carbon ions. The use of carbon or heavier ions is interesting for two reasons. First, whether the FLASH sparing effect in normal tissue is also observed at high-LET is very important to understand the physico-chemical mechanisms of the FLASH effect. Second, heavy ion therapy is limited by toxicity in the entrance channel, which may be reduced at ultra-high dose rates. Here we will present the most recent in vitro and in vivo experiments performed at HIT and GSI synchrotrons with ultra-high intensities of 12C-ions.ULTRA-HIGH DOSE RATE (FLASH) CARBON ION IRRADIATION: FIRST IN VITRO AND IN VIVO RESULTS
Abstract
Background and Aims
In this work, we present the results of first in vitro and in vivo studies for carbon ion beams irradiation that aim to investigate the biological effects delivered at ultra-high dose rate (FLASH).
Methods
The Heidelberg Ion-Beam Therapy Center (HIT) synchrotron, after technical adaptions, can reliably extract 5×108 12C ions within approximately 150 ms. This yields a dose of 7.5 Gy (homogeneity of ±5%) in a volume of at least 8 mm in diameter and a corresponding dose rate of 40-70 Gy s-1. Additionally, similar beam application but at 8 times higher beam intensity could be recently performed at GSI for carbon FLASH irradiations in mice models (Dose: 12-18 Gy, Dose-rate 60-100 Gy s-1).
Results
For the in vitro experiments a clonogenic survival assay and residual γH2AX foci analysis have been performed. The results of the survival assay demonstrate a significant FLASH sparing effect which is strongly oxygenation-dependent and is mostly pronounced at the concentration of 0.5% O2 but absent at 0% and 21% O2 (fig 1). The γH2AX results shows reduction in the residual foci signal at 1% O2.
The GSI in vivo irradiations of mice models could be successfully performed in the plateau and in the SOBP region (fig 2). The SIS18 synchrotron enables treatment of target volumes of typically 20 cm3 with 15 Gy in 150 ms. Larger volumes seem to be possible.
Conclusions
The in vitro experiments confirm FLASH sparing effect at low oxygen concentrations. The pre-clinical results from the very recent mice model experiments are currently under evaluation.
ADVANCED DOSIMETRY AND BIOPHYSICAL MODELING FOR PRECLINICAL FLASH RADIOTHERAPY
Abstract
Background and Aims
Since the oxygen depletion hypothesis has been recently challenged, the setup of a new joint project dedicated to an alternative mechanistic explanation of the FLASH effect, presently submitted to the Italian Association for Cancer Research (AIRC), will be presented. Our approach is a bottom up analysis linking radiation chemical based radicals description and DNA damage modeling studies. This should enable us to predict the irradiation parameters of absolute dose, and dose rate for which the effect could be verified.
Methods
We will develop point-like and two dimensional optical based methods for FLASH real time dosimetry using Cerenkov and radioluminescence light.
In a second phase a multiscale mechanistic description of ultrahigh dose rate induced damage including oxygen interplay and reactive oxygen species production and reactions will be developed. Our approach is based on chemical track structure Monte Carlo simulations and dedicated extensions of analytical biophysical models.
Results
We expect to obtain:
-Real time dosimetric methods to monitor FLASH beams for cells and mice irradiations. The same methods can be also translated to monitor FLASH delivery to human patients.
-A refined mechanistic description of the FLASH effect starting from basic radiation chemistry concepts in a biological environment. We will also provide in vitro and in vivo validation tests using two types of FLASH beams.
Conclusions
This work will contribute to unraveling the basic biological mechanisms of the FLASH effect and, at the same time, it will provide accurate real time dosimetric tools not available at the moment.
HITRIPLUS PROJECT: BUILDING A PAN-EUROPEAN HEAVY ION THERAPY RESEARCH COMMUNITY AND PROVIDING RESEARCH FACILITIES ACCESS
Abstract
Background and Aims
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HITRIplus (Heavy Ion Therapy Research Integration plus) is a multidisciplinary collaborative EU-funded project aiming to integrate and advance biophysics and medical research in cancer treatment with heavy ions. In parallel the broader objective is to provide radiation therapy community with cutting-edge tools to treat patients for improving survival rates and lowering recurrences with ions.
HITRIplus has built a consortium, coordinated by Sandro Rossi from CNAO, engaging all relevant stakeholders and for the first time bringing together all four European ion therapy centres with leading academic partners, research laboratories and innovative industrial partners. Together they all share the common vision to build a strong collaborative pan-European Heavy Ion Therapy Research Community. A strategic partner is the South-East European International Institute for Sustainable Technologies (SEEIIST), which federates eight countries in South-East Europe with the ambition to build a next generation heavy ion Research Infrastructure in the area.
HITRIplus as an infrastructure is built around the following major objectives:
1. To integrate, open up and broaden the leading European Research Infrastructure for the treatment of cancer with beams of ions, ranging from helium to carbon and to heavier ions.
2. To coordinate and strengthen the research programmes on heavy ion therapy of different European institutions, by promoting synergies, collaborations, innovation, knowledge transfer, new initiatives and sharing of tools and data.
3. To develop in a joint and coordinated way novel technologies to improve the accelerators and their ancillary systems that provide particle beams to this scientific community. These technologies will improve the present generation of facilities and will be the foundation for a next generation European design for ion therapy facilities.
4. To establish a European multidisciplinary community for heavy ion therapy research, aiming at improving treatment strategies and modalities by connecting physics and engineering with medicine, biology and biophysics, and to extend this community towards emerging European regions, addressing in particular new initiatives in South-East Europe.
5. To define the main technical features and the scientific programme of a future pan-European Research Infrastructure for medical and radiobiological research with heavy ion beams, to be built in South East Europe or in another European region.
This presentation will focus on highlighting the Transnational Access Pillar, coordinated by GSI, which brings together, for the first time ever, all the four dual heavy ion European centres in operation (CNAO, HIT, MedAustron and MIT) and open them to the medical and research community by offering transnational beam access. A fifth research facility providing access is GSI, which contributes by opening its biophysics research programme. The TA Clinical access will offer the opportunity to European hospitals and cancer institutes to refer their patients to these four clinical facilities and to share prospective clinical studies and patient follow-up. It will also allow the radiation oncologists to work together with their colleagues in multicentre prospective comparative studies to improve the knowledge both in heavy ion therapy and in classical radiation oncology through clinical research practice and combining treatment modalities. The TA Research access will attract universities, research centres, and hospitals for using the beam time and research facilities of the existing heavy ion centres.
During this presentation, information about the scope and how to access this beam will be shared, which will help to foster both clinical and pre-clinical research on heavy ions.
IN VITRO MEASUREMENTS OF PROTON RBE: A MULTI-CENTRIC COMPARISON OF EXPERIMENTAL PROCEDURES AND RESULTS
Abstract
Background and Aims
We present the current status and outcomes of the joint radiobiological experiment performed at eight European proton therapy centers or research institutes. The study aims to spot the potential differences in the in vitro proton RBE values measured by different groups sharing a similar setup and identify its causes.
Methods
A phantom and a protocol for sample preparation and post-processing are shared among the participants to ensure minimal differences in the biological part of the experimental procedure. In this phantom, V79 cells grow on the polyester slides that can be inserted at different depths, which enables their simultaneous irradiation at multiple positions within the radiation field. The setup is irradiated with proton beams with two SOBP configurations (6 cm, 6 Gy, and 4 cm, 8 Gy), followed by the reference photon irradiation (LINAC or x-ray), and the biological effect is evaluated using a colony-forming assay.
Results
The study is still ongoing, and the spread of data for measured cell survival is yet to be evaluated. However, some non-obvious differences in the experimental procedures and setups are already revealed, e.g. post-processing timing or varying dose distributions in the beam plateau/fall-off regions.
Conclusions
As an outcome of the experiment, we plan to summarize the details of the experimental procedure for biological experiments with proton beams, differing between the centers across Europe. Accounting for these details would help to harmonize future studies in the field.
This work was supported by EU Horizon2020 grant 730983 (INSPIRE).