Quantitative Assessment of 3D Dose Rate for Proton Pencil Beam Scanning FLASH Radiotherapy and Its Application for Lung Hypofractionation Treatment Planning

Simple Summary As pencil beam scanning (PBS) proton therapy delivers doses via spot-scanning, the dose rate quantification is very different from the electron and scattering proton techniques in FLASH radiotherapy. Currently, there is no consensus on the definition of the PBS proton therapy dose rate calculation for normal tissues and targets. This study focuses on the dose rate quantification of organs-at-risk and target based on three proposed dose rate metrics using proton transmission beams. The differences in dose rate metrics have led a large variation for organs-at-risk dose rate assessment and may result in a different correlation expectation between dose rate and biological effects for pre-clinical experiments. An awareness of the differences in proton PBS dose rate calculation is important to design experiments and clinical trials to uncover FLASH-RT's biological and physiological mechanisms. To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton therapy (IMPT) treatment planning using transmission beams. An in-house FLASH planning platform was developed to optimize transmission (shoot-through) plans for nine consecutive lung cancer patients previously planned with proton SBRT. Dose and dose rate calculation codes were developed to quantify three types of dose rate calculation methods (dose-averaged dose rate (DADR), average dose rate (ADR), and dose-threshold dose rate (DTDR)) based on both phantom and patient treatment plans. Two different minimum MU/spot settings were used to optimize two different dose regimes, 34-Gy in one fraction and 45-Gy in three fractions. The OAR sparing and target coverage can be optimized with good uniformity (hotspot < 110% of prescription dose). ADR, accounting for the spot dwelling and scanning time, gives the lowest dose rate; DTDR, not considering this time but a dose-threshold, gives an intermediate dose rate, whereas DADR gives the highest dose rate without considering any time or dose-threshold. All three dose rates attenuate along the beam direction, and the highest dose rate regions often occur on the field edge for ADR and DTDR, whereas DADR has a better dose rate uniformity. The differences in dose rate metrics have led a large variation for OARs dose rate assessment, posing challenges to FLASH clinical implementation. This is the first attempt to study the impact of the dose rate models, and more investigations and evidence for the details of proton PBS FLASH parameters are needed to explore the correlation between FLASH efficacy and the dose rate metrics.

Automated summary

This study focuses on quantifying the dose rate of organs-at-risk and targets based on three proposed proton PBS dose rate metrics, showing significant impact of differences in dose rate metrics on the assessment of organ-at-risk dose rate, posing challenges to the clinical implementation of FLASH. Additional investigations are needed to explore the correlation between FLASH efficacy and the dose rate metrics in proton PBS therapy.