Background and Aims

Range uncertainties remain the largest source of uncertainty in proton therapy and prevent taking full advantage of its superior dose conformity. To ensure optimal patient safety, daily quality assurance (QA) procedures are carried out each day before treatment begins, which are often time-consuming. In FLASH proton therapy, short treatment delivery times and high dose-rates mean that typical ionisation chamber-based dosimetry methods become unusable. FLASH dose-rates are currently estimated to be approximately 40 Gy/s or 600 nA to the patient.

The Quality Assurance Range Calorimeter (QuARC) is currently under development at UCL to provide fast, accurate, water-equivalent proton range measurements to speed up daily QA, which could also be used for range QA at FLASH dose-rates. The detector is a series of optically isolated plastic scintillator sheets that sample the proton energy deposition along its path length.

Methods

Each scintillator sheet is coupled to a photodiode that measures its light output directly. An analytical depth-light model is used to fit the data and recover the proton range. A preliminary beam test was conducted at UCLH using pencil beams between 70-110 MeV.

Results

The QuARC was found to consistently recover proton ranges with good accuracy, even with low levels of light. Live fitting of the captured data enables stable real-time range reconstruction at 40 Hz. Given its large dynamic range, measurements at FLASH dose rates are feasible, with an estimated factor 200 increase in light output.

Conclusions

Further measurements are required to fully characterise detector performance and determine light output with FLASH dose-rates.

Background and Aims

At PSI’s proton therapy facility PROSCAN, two novel compact cavity resonators for non-interceptive beam-size-independent monitoring have been developed. For the ongoing FLASH effect experiments at PROSCAN, the application of these monitors has been expanded to include dedicated real-time signal processing with the cooperation of Instrumentation Technologies.

Methods

This enhances PSI’s solution towards a non-interceptive online turn-key FLASH beam diagnostics system that could be customized for other particle therapy facilities. A major challenge in FLASH-beam conditions is the use of accurate dosimetry devices and the characterization of suitable detectors. Until now, interceptive monitors, such as ionization chambers have been used to measure the high beam currents. However, these monitors are prone to significant recombination and saturation effects with increased dose-rates, which also depend on the beam size. The resulting absolute dose accuracy issues will limit the use of such monitors for FLASH experiments. Cavity resonators do not suffer from such limitations and , since non-interceptive, do not disturb the beam. These advantages make them very attractive for FLASH measurements.

Results

To comply with the short FLASH pulses, Instrumentation Technologies’ processing electronics has been adapted to provide 1-millisecond measurement resolution to take advantage of the fast response (of few microseconds) that PSI's cavity monitors offer.

Conclusions

In this contribution, we report on the new processing chain's results for proton beam currents up to 400 nA (corresponding to FLASH dose-rates), the advantages this diagnostics system presents, and its potential future applications in FLASH particle therapy machines.

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.

Background and Aims

There are at least two very plausible radiobiological mechanisms for the oxygen effect in FLASH: 1) Directly, by depletion of oxygen at critical molecular sites directly changing the amount of radiation damage; 2) Indirectly by modifying physiologically mediated changes in response to radiation damage via alterations in repair and/or cell signaling. The overwhelming amount of radiation-induced damage that ultimately leads to cell death occurs in DNA. Oxygen directly radiosensitizes by reaction with transient intermediates in the DNA. Hypoxia also can modify damage from ionizing radiation inducing changes in signaling and in repair mechanisms that differ between tumors and normal tissues.

Methods

Radiobiological Principles

Results

Based on studies with cells there are lesions in DNA that have lifetimes as long as 10^-5 or 10^-6 seconds. The pertinent distance from which oxygen can diffuse to the sensitive site is 100-1000 nm assuming the diffusion rate of oxygen is 2.1x10^-5 cm²/sec within the environment around the DNA. Therefore a technique is needed that can follow the oxygen level with spatial resolution of the nucleus and a time scale of 10^-5 seconds or faster. No currently available method can do this directly. This might be done if detailed spatial distribution of oxygen inside the cell is known and the rate of oxygen depletion in a nucleus can be determined by a combination of direct measurements of oxygen, genomic alterations, and appropriate calculations.

Conclusions

Using established principles of radiation biology it should be feasible to rigorously determine if and how oxygen is involved in the mechanism of FLASH.

Background and Aims

Protons can be delivered at FLASH-RT dose rates, but the Gaussian-shaped scanning spot (σ≈3.74mm) is incapable of sparing other organs in mice irradiations due to the ~20mm size of mice. In this study, we develop and validate a novel collimator for high-throughput hemithoracic irradiations of mice using 250MeV protons delivered at FLASH-RT dose-rates.

Methods

We designed a brass collimator of 7.62cm width (~44cm water-equivalent-thickness) for 250MeV FLASH-RT protons (~38cm range in water). Six 13mm apertures were precision-machined to allow concurrent ipsilateral-lung irradiation of six-mice while sparing contralateral-lung, head-and-neck, and abdominal organs. EBT-XD Gafchromic film was used to measure dose profiles at various depths of solid-water below the apertures to assess radiation penumbra and field size. The RayStation treatment planning system was used to calculate dose volume histograms of the organs.

Results

At 20mm depth, the radiation field showed a sharp profile edge (~0.4mm penumbra) nearly identical to the 320kVp beam historically used to perform hemithorax irradiations. Compared to the standard technique, the collimator allows sparing of the other organs. For 10Gy prescribed dose to the ipsilateral-lung, the collimator lowers the mean dose to the contralateral-lung from 6.3 to 2.7Gy, to the heart from 8.4 to 5.8Gy, to the liver from 8.5 to 6.5Gy, and to the stomach from 3.8 to 1.8Gy.

Conclusions

We designed and constructed a collimator able to perform concurrent hemi-thoracic proton irradiations while sparing other organs. This technique replicates the historical kV x-ray technique and is a vast improvement over using the standard scanning proton beam technique without further collimation.