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 5×10^{8 12}C 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.

Background and Aims

Methods

Results

Conclusions

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.