Radiation dosimetry challenges for future clinical application of FLASH radiotherapy

Introduction
Each year, more than 10 million cancer patients are globally treated with radiotherapy which delivers a lethal radiation dose to the tumour using beams of ionizing radiation. Apart from the tumor, radiation dose is delivered to healthy tissue which represents a high risk for negative side effects. FLASH radiotherapy has the potential to significantly reduce these side effects. FLASH radiotherapy takes advantage of the so-called FLASH effect. This is the capability to spare healthy tissue up to 50 %, when the radiation dose is delivered at much higher dose-rates (> 40 Gy/s) than in conventional radiotherapy (0.1 Gy/s).
Challenge
For effective and safe treatment delivery, the beam of each of the more than 17.000 radiotherapy modalities worldwide, must be calibrated by measurement of the radiation dose (dosimetry) using secondary standard ionisation chambers and following the procedures of international dosimetry protocols (e.g. IAEA TRS-398). Secondary standards are calibrated against primary standard graphite and water calorimeters at national metrology institutes (NMIs) in low dose-rate 60Co reference beams.
FLASH radiotherapy requires dose delivery at a hundred times higher dose-rate than in conventional radiotherapy. This introduces a measurement challenge, because ionization chambers exhibit large non-linearities due to ion recombination effects at high dose-rates, while they are calibrated in the linear domain at low dose-rates.
Clinical facilities for FLASH radiotherapy under development are based on scanning proton beams with a continuous ultra-high-dose-rate (UHDR) and on static pulsed electron beams with an ultra-high dose-per-pulse (UHDPP). To achieve the same uncertainty level in dosimetry for these future FLASH facilities, metrology research is needed on primary dosimetry standards, recombination effects, secondary standards and reference fields.
The operational range of primary standards need to be extended to the high dose-rate domain in order to directly calibrate secondary standards under the clinical conditions. As NMI has the financial capacity to set up a scanning UHDR proton beam facilities (50–100 M€), here the approach for traceable dosimetry will be based on portable graphite and water calorimeters, which can be applied in clinical beams.
Enhanced understanding of ion recombination effects in secondary standards is needed by combining simulation models with experiments. These models can be used to develop new correction techniques for recombination effects, estimate uncertainties and to reduce the recombination effects in secondary standards by improving their design.
In contrast to the approach for scanning UHDR proton beams, traceable dosimetry in UHDPP electron beams, can be based on clinical like reference fields, which mimic the reference conditions of clinical UHDPP electron beams, and replacing the 60Co fields allowing for direct calibration of secondary standards in beams with properties close to clinical conditions.
Impact
The described improved metrology enables the clinical introduction of FLASH radiotherapy. This will impact global health care in terms of improved outcomes and quality of life for cancer patients receiving radiotherapy. In addition improved metrology will impact medical device industry, because manufacturers of FLASH radiotherapy facilities (global market for proton therapy facilities >€3bn) and of measurement equipment will be able to demonstrate compliance of their products.