Impact of intrafraction prostate motion on clinical target coverage in proton therapy: A simulation study of dosimetric differences in two delivery techniques

Abstract Purpose To investigate the dosimetric impact of prostate intrafraction motion on proton double‐scattering (DS) and uniform scanning (US) treatments using electromagnetic transponder‐based prostate tracking data in simulated treatment deliveries. Methods In proton DS delivery, the spread‐out Bragg peak (SOBP) is created almost instantaneously by the constant rotation of the range modulator. US, however, delivers each entire energy layer of the SOBP sequentially from distal to proximal direction in time, which can interplay with prostate intrafraction motion. This spatiotemporal interplay during proton treatment was simulated to evaluate its dosimetric impact. Prostate clinical target volume (CTV) dose was obtained by moving CTV through dose matrices of the energy layers according to prostate‐motion traces. Fourteen prostate intrafraction motion traces of each of 17 prostate patients were used in the simulated treatment deliveries. Both single fraction dose‐volume histograms (DVHs) and fraction‐cumulative DVHs were obtained for both 2 Gy per fraction and 7.25 Gy per fraction stereotactic body radiotherapy (SBRT). Results The simulation results indicated that CTV dose degradation depends on the magnitude and direction of prostate intrafraction motion and is patient specific. For some individual fractions, prescription dose coverage decreased in both US and DS treatments, and hot and cold spots inside the CTV were observed in the US results. However, fraction‐cumulative CTV dose coverage showed much reduced dose degradation for both DS and US treatments for both 2 Gy per fraction and SBRT simulations. Conclusions This study indicated that CTV dose inhomogeneity may exist for some patients with severe prostate intrafraction motion during US treatments. However, there are no statistically significant dose differences between DS and US treatment simulations. Cumulative dose of multiple‐fractions significantly reduced dose uncertainties.


| INTRODUCTION
Prostate cancer is one of the most common cancers among men.
When it is detected and treated at its early stage, disease control and patient survival are relatively high. 1 Proton therapy is one of the treatment modalities used in prostate cancer radiotherapy. Sharp distal dose fall-off and less integral dose are a couple of its intrinsic advantages. 2 There are three commonly used proton treatment delivery techniques: double scattering (DS), uniform scanning (US), and pencil-beam scanning (PBS). [3][4][5] PBS prostate treatment is available at some of the new proton therapy institutions; DS and US deliveries are used by some proton therapy clinics. DS and US deliver the radiation dose to the target as a spread-out Bragg peak (SOBP). 6 PBS treatment plans are inversely optimized and can be delivered through single-field uniform dose plans or multi-field optimizations plans. In DS delivery, the SOBP covers the entire clinical target volume (CTV) at a given instance (0.1 s interval for IBA system). Target intrafraction motion will cause CTV dose degradation due to target movement outside the SOBP or beam's eye view. On the other hand, in US and PBS delivery, energy layers are delivered in a distal to proximal direction; thus, there is a temporal-spatial variation of the radiation dose inside the treated volume during the treatment process. This interplay effect of prostate intrafraction motion on PBS treatment was simulated and studied by Tang et al. 7 In this study, the effects of prostate motion on dose delivery during DS and US treatment were simulated and studied using real patient prostate traces. The prostate CTV individual fraction dose distribution and 14-fraction cumulative dose distribution were obtained using 17 patient intrafraction motion traces in the 2 Gy per fraction simulations. For prostate stereotactic body radiotherapy (SBRT), five fractions with 7.25 Gy per fraction were simulated; both individual fraction and five fraction cumulative dose distributions were obtained. We evaluated how prostate dose distributions are affected by the interplay between prostate motion and the energy-layer delivery. When DS treatment is delivered, the range modulator rotates at 600 RPM. Depending on the modulation width, the proton beam current is turned on for a predetermined portion of the modulator track. Each step on the modulator track corresponds to an energy layer to be delivered. With the second scatter in the beamline to create a flat axial-beam profile, the entire SOBP is delivered in one revolution of the range modulator, which takes 0.1 s. Thus, at a given instance, an entire stationary target can be covered by the SOBP. In US treatment delivery, the second scatter is replaced by two sets of beam scanning magnets in the two orthogonal directions perpendicular to the beam axis. Each energy layer is delivered through magnetic sweeping of the beam spot in the two directions.

2.A | Proton therapy delivery techniques
At UFPTI, the scanning frequency is 3 Hz in the gantry rotation axis direction and 30 Hz in its orthogonal direction. There is multiple repainting of each energy layer. Furthermore, the range modulator is static during the delivery of each energy layer and only rotates when beam is off between the deliveries of the energy layers. The energy layers are delivered sequentially from the most distal to the most proximal ones. At a given instance, either a nonuniform dose is delivered to the entire target (when the most distal layer is delivering) or only part of the target receives the radiation dose (all other layers).
Using the US technique, the maximum beam range is increased to 32.4 cm and the treatable field size is increased to 30 cm by 40 cm.
Therefore, the US technique can treat some deep-seated tumors as well as extremely large targets. However, compared to DS delivery, US delivery is potentially more susceptible to the spatial-temporal interplay due to target motion and nonuniform target dose delivery.
When the target motion is in the beam direction, part of the target can be over-irradiated by different layers, or it can be underdosed by missing irradiation from an energy layer, depending on the motion characteristics and layer-delivery timing. 9

2.B | Prostate traces
Prostate-motion traces acquired using a Calypso electromagnetic

2.C | Prostate proton treatment simulation
At UFPTI, left and right lateral or lateral-oblique beams are often used to treat prostate patients. 12 All of these patients have saline dose matrices of the DS treatment plan from Eclipse treatment planning system, 3D dose matrices of each individual energy layer of the treatment beam from the US treatment plan, and prostate-motion traces from the electromagnetic transponder system were imported into MATLAB. The prostate-motion traces were down-sampled from a resolution of 0.1 s to 1 s. The single fraction dose of the prostate CTV can be calculated as following:  3 | RESULTS Figure 2 shows the prostate-motion traces of two treatment frac-      Table 2 shows DVHs for the 14-   Table 3  Even though the proton treatment simulation incorporated the prostate motion and energy layer delivery timing to investigate the impact of intrafraction motion on prostate CTV dosimetry, not all the details of the US delivery were incorporated in the simulation.

2.D | Prostate motion dosimetry
For example, the scanning frequencies of 3 Hz in the gantry rotation axis direction and 30 Hz in its orthogonal direction as well as the repainting of each energy layer were not simulated. We believe that rapid-beam spot scanning and repainting of each energy layer equivalently created a quasi-instantaneous dose cloud for each energy layer. Thus, in US delivery simulation, moving the prostate through the dose matrix of each energy layer based on its time weight is dosimetrically adequate and accurate.

| CONCLUSION
In this study, we simulated both DS and US proton treatment of prostate using real-patient prostate-motion traces and evaluated dosimetric impact of intrafraction motion on both delivery techniques.
The fraction dose analyses indicated that CTV dose degradation due to prostate intrafraction motion is patient and fraction specific. Severe intrafraction prostate motion can cause CTV hot and cold spots in US treatments, whereas it only causes CTV underdosing in DS treatments. However, no statistically significant dose differences were observed between the two treatment delivery techniques. The cumulative dose of several simulated treatment fractions showed that the magnitude of the CTV dose degradation was reduced and generally lies within a clinically acceptable range from planned dose distributions. Nevertheless, the effects of target intrafraction motion can be a concern for other, more dynamic targets.

CONF LICT OF I NTEREST
No conflicts of interest.