Instantaneous in vivo distal edge verification in intensity-modulated proton therapy by means of PET imaging

Intensity-modulated proton therapy (IMPT) holds promise for improving outcomes in head-and-neck cancer (HNC) patients by enhancing organ-at-risk (OAR) sparing. A key challenge in IMPT is ensuring an accurate dose delivery at the distal edge of the tumor, where the steep dose gradients make treatment precision highly sensitive to uncertainties in both proton range and patient setup. Thus, IMPT conformality is increased by incorporating robust margins in the treatment optimization. However, an increment in the plan robustness could lead to an OAR overdosing. Therefore, an accurate distal edge verification during dose delivery is crucial to increase IMPT conformality by reducing optimization settings in treatment planning.

This work aims to evaluate, in a quasi-clinical setting, a novel approach for accurate instantaneous proton beam distal edge verification in IMPT by means of spot-by-spot positron emission tomography (PET) imaging.

An anthropomorphic head and neck phantom CIRS-731 HN was irradiated at the head and neck region. The targets were defined as 4 cm diameter spheres. A 60-ms delay was introduced between the proton beam spots in order to enable the spot-by-spot coincidence detection of the 511-keV photons resulting from positron annihilation following the positron emission from very short-lived positron-emitting, mainly ¹²N (T_1/2  = 11.0 ms). Additionally, modified irradiations were carried out using solid water slabs of 2 and 5 mm thickness in the beam path to assess the precision of the approach for detecting range deviations. The positron activity range (PAR) was determined from the 50% distal fall-off position of the 1D longitudinal positron activity profile derived from the 2D image reconstructions. Furthermore, Monte Carlo (MC) simulations were performed using an in-house RayStation/GATE MC framework to predict the positron activity images and verify the PAR measurements.

PAR measurements achieved a precision between 1.5 and 3.6 mm (at 1.5σ clinical level) at the beam spot level within sub-second time scales. Measured PAR shifts of 1.6-2.1  and 4.2--.7 mm were observed with the 2- and 5-mm thickness range shifters, respectively, aligning with the corresponding proton dose range (PDR) shifts of 1.3-1.8 and 3.9-4.3 mm. The simulated PAR agrees with the measured PARs, showing an average range difference of ∼0.4 mm.

This study demonstrated the feasibility of instantaneous distal edge verification using PET imaging by introducing beam spot delays during dose delivery. The findings represent a first step toward the clinical implementation of instantaneous in vivo distal edge verification. The approach contributes to the development of real-time range verification aimed at improving IMPT treatments by mitigating range and setup uncertainties, thereby reducing dose to organs-at-risk and ultimately enhancing patient outcomes.