Cancer is on course to become the leading cause of death worldwide by 2040. Establishing innovative treatment modalities is, therefore, a major 21st century health challenge. Radiotherapy (RT) is a fundamental component of our current ability to effectively treat tumours and control their growth. Currently the most common form of RT involves the use of x-rays to treat the tumour. In addition to this, proton and ion beams have been used to treat deep-seated tumours whilst reducing the damage to surrounding healthy tissue. Although accelerated electrons are widely used to generate X-rays for radiotherapy, electrons are less frequently used directly because low energy electrons have a limited penetration range and are mostly for the treatment of superficial tumours, thus limiting their clinical applicability.
Recently, studies involving ultra-high dose rate (mean dose rate above 100 Gy/s) delivery of ionising radiation, termed FLASH radiotherapy (FLASH-RT), have uncovered some unexpected but possible therapeutic benefits that have caused tremendous excitement in the radio-oncology field. Data appear to show that FLASH-RT affords significant normal tissue sparing without compromising tumour control.
In addition, the idea of using very high-energy (50-250 MeV) electron (VHEE) beams for RT has gained interest, since electrons with higher energies can travel deeper into the patient. The advantages of VHEE are that the depth–dose profile from the electrons is flatter than the quasi-exponential dose given by X-rays, and in addition, the delivered electrons may be focused and steered in ways that are not possible for X-rays. One other potential benefit is that VHEE can operate at very high dose rates, possibly compatible with the generation of the FLASH effect. The challenge until recently has been the difficulty in obtaining high-energy electrons using compact accelerators. However, the development of high-gradient cavities for linear colliders, such as the Compact Linear Collider (pictured right), has meant that using VHEE beams for RT has become a feasible possibility.
Due to this increase in interest, the production of VHEE beams for RT was the subject of the VHEE2020 International Workshop, organised by CERN, which took place from 5th - 7th October 2020. More than 400 scientists with diverse backgrounds, from clinicians to biologists and accelerator physicists to dosimetry experts, several of whom were from the JAI, gathered virtually to evaluate and discuss the perspectives of this novel technique. The workshop followed a similar one organised in 2017 in Daresbury with the large increase in attendance demonstrating the increasing interest in the field.
Topics covered at the workshop included state-of-the-art technological advances, biological and clinical aspects, what is needed to exploit VHEE for RT and FLASH clinically, as well the future industrial perspectives for the field.
Many challenges, both technological and biological, have to be addressed for the ultimate goal of using VHEE and VHEE-FLASH as an innovative modality for effective cancer treatment with minimal damage to healthy tissues. All of these topics were thoroughly discussed in the different sessions of VHEE2020. Talks given in the workshop outlined the current state of research in the VHEE field, what successful studies had been undertaken into VHEE and FLASH RT, what challenges have been faced by researchers in recent years and what the future outlook is for the field.
It was clear from the discussion that VHEE has the potential to provide a major input in our quest to fight cancer globally, but that many challenges have to be overcome first.
For example, current preclinical trials into the efficacy of FLASH-RT, on both animal subjects and humans, have shown exciting results, with potentially significant advantages in the treatment of tumours compared to conventional RT. However, it was noted that these results must be taken with caution as they only involved low-energy electron beams, which would not allow the treatment of deep seated tumours. One of the key aims set out for the future was to extend these experimental studies into the VHEE regime.
From the accelerator technology point of view, an important aim is to assess the possibility of focusing and transversely scanning the beam, thereby overcoming the disadvantages associated in the past with low energy electron and photon beam irradiation. In particular for VHEE-FLASH it will be necessary to ensure that the biological effect is maintained. Another major challenge for VHEE-FLASH is the delivery of a very high dose-rate, possibly over a large area, providing a uniform dose distribution throughout the target. The stability, reliability and repeatability are other mandatory ingredients for accelerators to be operated in a medical environment and so must be studied further. Of particular importance is the development of reliable on-line dosimetry for very high dose rates, a regime not adapted to the standard dosimetry techniques currently used in RT.
From a more general viewpoint, the parameter window in which the FLASH effect takes place has still to be thoroughly defined, as well as its effectiveness as a function of the physical parameters of the electron beam. Finally, a clear understanding of the underlying biological processes will likely prove to be essential in order to fully optimize the FLASH RT technique.
For these challenges to be met, a lot of future work must go into using test beam facilities in order to experimentally characterise and assess properties of VHEE beams and the ability to produce the FLASH effect. It is also important to demonstrate that the properties of the electron beams are independent of the way they are produced, (RF linac or LPA technologies). A number of experimental test facilities are already available to perform these ambitious objectives: the CERN Linear Electron Accelerator for Research (CLEAR), so far unique in being able to provide beams of both high-energy and high-charge. In addition, VELA-CLARA at Daresbury, PITZ at DESY and ELBE-HZDR using superconducting RF technology at Dresden are becoming available.
Oxford DPhil student, Luke Dyks (pictured), attended the workshop,
For me as a young researcher it’s very exciting to be working in a field that is so dynamic. Some of the ideas discussed at the workshop have great promise and I feel privileged to have to opportunity to contribute to their development. I can’t wait to get my teeth into them!
Despite the number of necessary developments highlighted at the meeting, there was an air of cautious optimism that with a well-directed, consistent effort to fully understand the physical processes underlying VHEE-RT and FLASH, the challenges could be overcome and operational medical VHEE facilities could be designed and built in the future.
Luke Dyks and Manjit Dosanjh