###### Abstract  
The interplay effect is a challenge when using proton scanning beams for the treatment of thoracic and abdominal cancers. The aim of this study was to evaluate the facility-specific interplay effect in terms of dose distortion and irradiation time for different beam delivery modalities, including free breathing (FB) irradiation, rescanning, deep inspiration breath-hold (DIBH), and respiratory gating. This study was carried out at a synchrotron-based facility with spot-scanning beam delivery. A motion phantom with a radiochromic film was used to measure dose distributions. Regular and irregular motion patterns were studied. Dose homogeneity and the gamma index were calculated to quantify the interplay effect. The interplay effect significantly decreased the homogeneity and gamma passing rate by 12% and 46%, respectively, when FB irradiation without motion mitigation was used for 20 mm peak-to-peak motion. Rescanning and DIBH partially mitigated the distortions but doubled the irradiation time, while gating provided the superior dose distribution with only a 25% increase in time compared to FB irradiation without mitigation. The interplay effect was a function of motion amplitude and varied with the beam delivery modality. Gating may be a more preferable technique for the synchrotron-based facility in terms of minimizing dose distortion and treatment time. interplay effect; spot-scanning proton therapy; 4D motion phantom; intrafractional target motion; motion mitigation +
Footnote †: journal: Medical  
has a similar property but within a fraction. It consists of multiple repeated scans of the entire target volume [15] or individual iso-energy layers [16] with a low-intensity beam. It randomizes the phase of beam delivery to the spot relative to the phase of target motion, resulting in the randomization of the position of hot and cold spots in individual rescans and their statistical averaging when the total dose per fraction is delivered. Rescanning can be introduced into free breathing (FB) irradiation either separately or in combination with respiratory gating [7; 17; 18]. When rescanning is used separately, respiratory monitoring is not required, with the exception of phase-controlled rescanning [19]. Another common approach is deep inspiration breath-hold (DIBH) irradiation, which consists of delivering the beam while the patient holds their breath, rendering the tumor nearly immobile [20]. It is actively used in the treatment of left-sided breast cancer [21] and lung cancer [22]. The DIBH technique requires real-time respiratory monitoring with spirometric [23] or optical [24] devices to detect the breath-hold (BH) phase. In addition, audiovisual feedback is usually provided to improve the inter-BH repeatability of the tumor position [25]. The tumor position during the BH phase may be unstable due to its inter-BH variations between consecutive deep breaths and its intra-BH residual motion. DIBH treatment may be limited for some patients because the inter-BH and intra-BH displacements may be greater than 8 mm [24] and 5 mm [26], respectively. For patients with regular breathing, gating may be preferable to DIBH [27]. This approach consists of gated FB delivery to the moving tumor within a gating window where residual motion is insignificant, more often at the end of expiration. It allows for the margins between a clinical target volume (CTV) and a planning target volume (PTV) to be minimized without modifying the breathing pattern as in DIBH. Respiratory gating requires the real-time monitoring of respiration with the smallest possible system time delay [28] to generate the gate-on/off signals for an accelerator. The interplay effect has previously been studied using treatment planning systems (TPS) or four-dimensional (4D) motion phantoms for FB irradiation [4; 8; 11; 29], rescanning [15; 30; 31], DIBH [32], respiratory gating [27], and a combination of rescanning and gating [17].