Zapien-Campos Brian, Ahmadi Ganjeh Zahra, Perotti-Bernardini Giuliano, Free Jeffrey, Both Stefan, Dendooven Peter
Particle Therapy Research Center (PARTREC), Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Med Phys. 2025 Jul;52(7):e17850. doi: 10.1002/mp.17850. Epub 2025 May 2.
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 N (T = 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.
调强质子治疗(IMPT)有望通过提高危及器官(OAR)的保护水平来改善头颈癌(HNC)患者的治疗效果。IMPT的一个关键挑战是确保在肿瘤远端边缘精确输送剂量,在此处陡峭的剂量梯度使治疗精度对质子射程和患者摆位的不确定性高度敏感。因此,通过在治疗优化中纳入稳健的边界来提高IMPT的适形性。然而,计划稳健性的增加可能导致OAR剂量过量。因此,在剂量输送过程中进行准确的远端边缘验证对于通过减少治疗计划中的优化设置来提高IMPT适形性至关重要。
本研究旨在在准临床环境中评估一种通过逐点正电子发射断层扫描(PET)成像在IMPT中进行精确的瞬时质子束远端边缘验证的新方法。
使用拟人化的头颈体模CIRS-731 HN对头颈部区域进行照射。靶区定义为直径4 cm的球体。在质子束点之间引入60 ms的延迟,以便能够对极短寿命的主要发射正电子的N(T = 11.0 ms)发射正电子后正电子湮灭产生的511 keV光子进行逐点符合检测。此外,在束流路径中使用2 mm和5 mm厚的固体水板进行了改进照射,以评估检测射程偏差方法的精度。正电子活度范围(PAR)由二维图像重建得到的一维纵向正电子活度分布的50%远端下降位置确定。此外,使用内部RayStation/GATE蒙特卡罗(MC)框架进行了MC模拟,以预测正电子活度图像并验证PAR测量结果。
在亚秒时间尺度内,PAR测量在束斑水平上达到了1.5至3.6 mm(在1.5σ临床水平)的精度。分别使用2 mm和5 mm厚度的射程移位器观察到PAR测量移位为1.6 - 2.1 mm和4.2 - 4.7 mm,与相应的质子剂量范围(PDR)移位1.3 - 1.8 mm和3.9 - 4.3 mm一致。模拟的PAR与测量的PAR一致,平均射程差异约为0.4 mm。
本研究通过在剂量输送过程中引入束斑延迟,证明了使用PET成像进行瞬时远端边缘验证的可行性。这些发现代表了朝着瞬时体内远端边缘验证的临床应用迈出的第一步。该方法有助于实时射程验证的发展,旨在通过减轻射程和摆位的不确定性来改善IMPT治疗,从而减少对危及器官的剂量并最终提高患者的治疗效果。