Treatment planning for Flash radiotherapy: General aspects and applications to proton beams

Abstract

The increased radioresistence of healthy tissues when irradiated at very high dose rates (known as the Flash effect) is a radiobiological mechanism that is currently investigated to increase the therapeutic ratio of radiotherapy treatments. To maximize the benefits of the clinical application of Flash, a patient‐specific balance between different properties of the dose distribution should be found, that is, Flash needs to be one of the variables considered in treatment planning. We investigated the Flash potential of three proton therapy planning and beam delivery techniques, each on a different anatomical region. Based on a set of beam delivery parameters, on hypotheses on the dose and dose rate thresholds needed for the Flash effect to occur, and on two definitions of Flash dose rate, we generated exemplary illustrations of the capabilities of current proton therapy equipment to generate Flash dose distributions. All techniques investigated could both produce dose distributions comparable with a conventional proton plan and reach the Flash regime, to an extent that was strongly dependent on the dose per fraction and the Flash dose threshold. The beam current, Flash dose rate threshold, and dose rate definition typically had a more moderate effect on the amount of Flash dose in normal tissue. A systematic estimation of the impact of Flash on different patient anatomies and treatment protocols is possible only if Flash‐specific treatment planning features become readily available. Planning evaluation tools such as a voxel‐based dose delivery time structure, and the inclusion in the optimization cost function of parameters directly associated with Flash (e.g., beam current, spot delivery sequence, and scanning speed), are needed to generate treatment plans that are taking full advantage of the potential benefits of the Flash effect.

Treatment planning considerations for the development of FLASH proton therapy

“…While the full characterisation of the basic pre-clinical parameters required to produce a FLASH effect remain under investigation, any work in trying to meet these requirements in a more complex clinical scenario could be considered futile. However, given the flexibility and research capability of modern treatment planning systems and radiobiological models, a number of groups have set out to explore different treatment options for FLASH, and identify the most promising scenarios given both our current understanding and emerging pre-clinical data [4, 23,24,37,38,39]. Due to the ability of commercial proton systems to deliver treatment fields at ultra-high dose rates, the vast majority of FLASH treatment planning investigations have focused on FLASH delivery using proton beams.…”

“…Due to the ability of commercial proton systems to deliver treatment fields at ultra-high dose rates, the vast majority of FLASH treatment planning investigations have focused on FLASH delivery using proton beams. Based on preclinical evidence, the requirement to trigger the FLASH effect in these treatment planning studies to date are generally assumed to be a minimum dose rate of 40 Gy/s [4, 23,24], with some studies also considering a minimum dose of 4-10 Gy [37,38,39].…”

“…Another approach is the sliding window dose rate calculation, where an evaluation window is moved over the dose delivery time trace per voxel for each field, and the combination of FLASH dose rate and dose thresholds determines the time window width (e.g. 40 Gy/s and 4 Gy thresholds imply a 100 ms time window) [39].…”

“…Another option is the proposed use of 'disjoint field optimisation', where each field is used to deliver the full prescribed dose to one part of the tumour, without overlap with other fields [39]. The radiobiological implications of such techniques should be weighed up against any potential FLASH sparing.…”

“…Most treatment planning studies to date aimed to achieve FLASH dose rates at all points in a treatment plan, under the assumption that only the normal tissue will be spared [23,38,39,49]. However the ways in which this differential response could be exploited for clinical outcome are yet to be seen.…”