Range shift verification in spot scanning proton therapy using gamma electron vertex imaging

In proton therapy, a highly steep distal dose penumbra can be utilized for dose conformity, given the Bragg peak characteristic of protons. However, the location of the Bragg peak in patients (i.e., the beam range) is very sensitive to range uncertainty. Even a small shift of beam range can produce a significant variation of delivered dose to tumor and normal tissues, thus degrading treatment quality and threatening patient safety. This range uncertainty issue, therefore, is one of the important aspects to be managed in proton therapy.

For better management of range uncertainty, range verification has been widely studied, and prompt gamma imaging (PGI) is considered one of the promising methods in that effort. In this context, a PGI system named the gamma electron vertex imaging (GEVI) system was developed and recently upgraded for application to pencil-beam scanning (PBS) proton therapy. Here, we report the first experimental results using the therapeutic spot scanning proton beams.

A homogeneous slab phantom and an anthropomorphic phantom were employed. Spherical and cubic planning target volumes (PTVs) were defined. Various range shift scenarios were introduced. Prompt gamma (PG) measurement was synchronized with beam irradiation. The measured PG distributions were aggregated to improve the PG statistics. The range shift was estimated based on the relative change of the centroid in the measured PG distribution. The estimated range shifts were analyzed by range shift mapping, confidence interval (CI) estimation, and statistical hypothesis testing.

The range shift mapping results showed an obvious measured range shift tendency following the true shift values. However, some fluctuations were found for spots that had still-low PG statistics after spot aggregation. The 99% CI distributions showed clearly distributed range shift measurement data. The overall accuracy and precision for all investigated scenarios were 0.36 and 0.20 mm, respectively. The results of one-sample t-tests confirmed that every shift scenario could be observed up to 1 mm of shift. The ANOVA results proved that the measured range shift data could be discriminated from one another, except for 16 (of 138) comparison cases having 1-2 mm shift differences.

This study demonstrated the feasibility of the GEVI system for measurement of range shift in spot scanning proton therapy. Our experimental results showed that the proton beam can be measured up to 1 mm of range shift with high accuracy and precision. We believe that the GEVI system is one of the most promising PGI systems for in vivo range verification. Further research for application to more various cases and patient treatments is planned.