Against a dark background is the Mobetron clinical linear accelerator. A tall, white, box-like instrument on wheels surrounded in the picture with glowing lines
Case Study Overview

Monitoring of ultra-high dose rate electron beams for advanced cancer treatment

Radiotherapy uses ionising radiation such as high-energy photons, protons or electrons to target cancer. Recently, a new type of treatment modality has emerged, where the prescribed dose is delivered to the tumour in less than a second using particle beams with ultra-high dose rates. This reduces radiation-induced side effects. However, conventional dosimetric procedures and tools struggle to work with this promising anticancer tool.

Challenge

Cancer is among the leading causes of death worldwide. Surgery is a common treatment but where it may be difficult, or cause disfigurement, it is often supplemented or replaced with radiotherapy (RT). In RT, medical accelerators or irradiating sources deliver ionising radiation, such as high-energy photons, protons, or electrons, to the tumour site to kill cancerous cells. Whilst effective, many patients experience severe toxicity due to damage to healthy cells around the tumoral site. To reduce this, radiation is often fractionated in small doses in multiple treatment sessions over the course of 5-6 weeks, which lets healthy tissue recover. The irradiation during one fraction takes several minutes at conventional dose rates (the delivered radiation dose per time interval).

Recently, Ultra-High Dose Rate (UHDR) RT has emerged as novel procedure, where the total dose is delivered by only a few beam pulses from the accelerator within a time interval of less than one second. Evidence suggests that this so called “FLASH” therapy spares normal tissue in comparison to conventional RT whilst maintaining the same tumour control.

However, the beam monitors based on transmission ionisation chambers currently used in medical accelerators become saturated under the pulsed ultra-high dose rate used in in FLASH RT - and accurate beam monitoring and control becomes challenging.

New methods for dosimetry and beam monitoring for FLASH RT were required to help advance this important medical technique.

Solution

During the UHDpulse project, the partner Lausanne University Hospital (CHUV) worked with the company IntraOp to implement a monitoring system able to record doses of beam pulses during FLASH RT with electrons without affecting the beam. A proof-of-concept study using a research accelerator (eRT from PMB) was promising and a similar system was validated with a clinical linear accelerator (LINAC) modified for FLASH RT, the Mobetron from IntraOp.

At CHUV, two Beam Current Transformers (BCT), consisting of high-quality circular coils, were mounted on the head of the Mobetron to monitor the electron beam pulses. When the electron beam passes through the BCTs, a current is induced, proportional to the charge of the electron beam pulses. This can be used for real-time and non-destructive temporal readout of the beam when carefully calibrated.

System parameters were thoroughly investigated in both conventional and UHDR modes, including beam intensity, pulse repetition rate, and pulse duration. The short and long-term stabilities were validated, and a beam charge-to-absorbed dose relationship developed. This ratified the use of BCTs for monitoring and real-time dose control in FLASH therapy, with the advantage that the absorbed dose can be obtained during radiation delivery with UHDR.

Impact

IntraOp is a leading innovator of electron therapy devices and its flagship product, the Mobetron, has been installed in hospitals around the world for treating skin and other cancers. Following the work at CHUV within the framework of the UHDpulse project, and independent verification of BCT in its own laboratories, the company has since integrated these induction coils into the head of the Mobetron as a beam monitor. This instrument, the first mobile, self-shielded electron-beam LINAC for delivering RT to patients during surgery, can now also be used for research into electron FLASH therapies.

Project partner CHUV were the first to realise the potential of FLASH therapy in 2014 and together with IntraOP started the first phase-1 FLASH trial with the Mobetron on a skin cancer patient in 2021 and the first randomized trial comparing conventional RT with FLASH on patients with localised carcinomas in 2023.

The use of portable, FLASH LINACs like the Mobetron has the potential to revolutionise point of care cancer treatment – improving patient outcomes whilst minimising side-effects in a  cost-effective manner. In addition, the outputs of the UHDpulse project will enable manufacturers to develop improved UHDR instrumentation to benefit both European competitiveness and the health of its citizens.

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Metrology for advanced radiotherapy

In the UHDpulse project, reference radiation fields for electron beams with ultra-high dose rates (UHDR) were developed, optimised, commissioned and compared. Conventional dosimetry techniques were assessed for FLASH therapy, such as ionisation chambers, calorimeters, Fricke-, Alanine- and film dosimeters. New approaches were developed, including a diamonddiode dosimeter, the first silicon carbide diodes suitable for ultra-high DPP real-time dosimetry and a primary standard proton calorimeter.

The latter instrument, with an uncertainty of 0.9% in line with conventional instruments, was used in the first-ever human trials in 2020 for FLASH proton UHDR (FAST-01). Beam Current Transformers for UHDR control were also investigated, and commercial companies are now offering inductive monitoring as upgrades.

By providing the metrological tools needed to perform traceable dosimetric measurements in clinical or preclinical UHPDR particle beams, the project has allowed improved comparability between studies carried out in different facilities with different radiation modalities.

In the long-term this will ensure the safety and efficacy of UHDR therapies for cancer patients.

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