Abstract
Simple SummaryAs 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.
Highlights
Pre-clinical investigations have shown that ultra-high dose rate (>40 Gy/s) electron beam radiotherapy (FLASH radiation therapy (RT)) leads to fewer radiation-induced toxicities, but is as effective as conventional dose rate radiotherapy regarding tumor control [1,2]
The dose-averaged dose rate (DADR) method weighted the dose without considering the spot duration and scanning time; the dose rate was uniform across the scanning map with the highest dose rate in most outside spots
The dose threshold dose rate (DTDR) method uses a 0.1 Gy dose-threshold to exclude the spot low dose tail from the dose rate calculation, making the dose rate distribution a regular pattern. This dose rate pattern is similar to the spot map, but the highest DTDR occurs between the spots not at the spot center, which is different from the results of the averaged dose rate (ADR) method
Summary
Pre-clinical investigations have shown that ultra-high dose rate (>40 Gy/s) electron beam radiotherapy (FLASH radiation therapy (RT)) leads to fewer radiation-induced toxicities, but is as effective as conventional dose rate radiotherapy regarding tumor control [1,2]. With growing interest in this novel dose delivery approach, recent studies have reported that FLASH-RT achieves enhanced normal tissue protection compared to conventional-RT in the mouse brain, pig skin, and cat experiments [3,4,5]. A proof-of-concept FLASH-RT experiment, using a clinical proton system, was performed at the Institut Curie France, where a max dose rate of 40 Gy/s was reached with scattering delivery techniques [8]. Beyreuther et al studied the FLASH effect through irradiating zebrafish embryo using the scattering technique on an IBA proton system [10]. Researchers from the University of Pennsylvania reported their FLASH progress on an IBA proton system, where a dose rate > 100 Gy/s was reached on a small animal radiation therapy platform via scattering systems [11]. The effects of FLASH irradiation using pencil beam scanning (PBS) proton irradiation in a Varian ProBeam system were reported by Cunningham et al [12]
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