Baltazar Filipa, Longarino Friderike K, Stengl Christina, Liermann Jakob, Mein Stewart, Debus Jürgen, Tessonnier Thomas, Mairani Andrea
Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg, Germany.
Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Med Phys. 2025 Mar;52(3):1746-1757. doi: 10.1002/mp.17569. Epub 2024 Dec 10.
Clinical carbon ion beams offer the potential to overcome hypoxia-induced radioresistance in pancreatic tumors, due to their high dose-averaged Linear Energy Transfer (LETd), as previous studies have linked a minimum LETd within the tumor to improved local control. Current clinical practices at the Heidelberg Ion-Beam Therapy Center (HIT), which use two posterior beams, do not fully exploit the LETd advantage of carbon ions, as the high LETd is primarily focused on the beams' distal edges. Different LETd-boosting strategies, such as Spot-scanning Hadron Arc (SHArc), could enhance LETd distribution by concentrating high-LETd values in potential hypoxic tumor cores while sparing organs at risk.
This study aims to investigate and verify different LETd-boosting strategies using an anthropomorphic pancreas phantom.
Various LETd-boosting strategies were investigated for a cylindrical and a pancreas-shaped target in an anthropomorphic pancreas phantom. Treatment plans were optimized using single field optimization (SFO) or multi field optimization (MFO), with objective functions based on either physical dose (Phys), relative biological effectiveness (RBE)-weighted dose, or a combination of RBE and LETd-based objectives (LETopt). The LETd-boosting planning strategies were optimized with the goal of increasing the minimum LETd in the tumor without compromising its homogeneous dose coverage. Beam configurations investigated included the two-beam in-house clinical standard (2-SFO, 2-SFO and 2-MFO), a three-beam configuration (3-MFO and 3-MFO) and SHArc (SHArc, SHArc and SHArc) using step-and-shoot delivery. The different plans were verified using an anthropomorphic pancreas phantom at HIT and compared to treatment planning system (TPS) predictions.
All investigated LETd-boosting strategies altered the LETd distribution while meeting optimization goals and constraints, resulting in varying degrees of LETd enhancement. For the cylindrical volume, the SHArc plan resulted in the highest LETd concentration in the tumor core, with the minimum LETd in the GTV scaling up to 91 keV/µm. For the pancreas-shaped volume, however, the 3-MFO achieved a higher minimum LETd in the GTV than SHArc (75.6 and 62.3 keV/µm, respectively). When combining SHArc with LETd optimization, a minimum LETd of 76.3 keV/µm was achieved, suggesting a potential benefit from this combined approach. Most dosimetric verifications showed dose deviations to the TPS within a 5% range, for both beam-per-beam and total dose. LETd-optimized and SHArc plans exhibited slightly higher mean dose deviations (2.0%-4.6%) compared to the standard RBE-based plans (<1.5%).
This study demonstrated the feasibility of enhancing LETd in pancreatic tumors using carbon ion arc delivery coupled with LETd optimization. The possibility of delivering these plans was verified through irradiation of an anthropomorphic pancreas phantom, which showed agreement between dose measurements and predictions.
临床碳离子束有潜力克服胰腺肿瘤中因缺氧导致的放射抗性,这归因于其高剂量平均线能量转移(LETd),因为先前的研究已将肿瘤内的最低LETd与改善局部控制联系起来。海德堡离子束治疗中心(HIT)目前的临床实践使用两束后向射束,并未充分利用碳离子的LETd优势,因为高LETd主要集中在射束的远端边缘。不同的LETd增强策略,如点扫描强子弧(SHArc),可以通过将高LETd值集中在潜在的缺氧肿瘤核心同时保护危及器官,来增强LETd分布。
本研究旨在使用拟人化胰腺体模研究并验证不同的LETd增强策略。
在拟人化胰腺体模中,针对圆柱形和胰腺形状的靶区研究了各种LETd增强策略。使用单野优化(SFO)或多野优化(MFO)对治疗计划进行优化,目标函数基于物理剂量(Phys)、相对生物效应(RBE)加权剂量或基于RBE和LETd的目标组合(LETopt)。LETd增强计划策略的优化目标是在不影响肿瘤均匀剂量覆盖的情况下提高肿瘤内的最低LETd。研究的射束配置包括两束内部临床标准配置(2-SFO、2-SFO和2-MFO)、三束配置(3-MFO和3-MFO)以及使用步进式射束投照的SHArc(SHArc、SHArc和SHArc)。在HIT使用拟人化胰腺体模对不同计划进行验证,并与治疗计划系统(TPS)预测结果进行比较。
所有研究的LETd增强策略在满足优化目标和约束条件的同时改变了LETd分布,导致LETd有不同程度的增强。对于圆柱形体积,SHArc计划在肿瘤核心产生了最高的LETd浓度,GTV中的最低LETd扩大到91 keV/μm。然而,对于胰腺形状的体积,3-MFO在GTV中实现了比SHArc更高的最低LETd(分别为75.6和62.3 keV/μm)。当将SHArc与LETd优化相结合时,实现了76.3 keV/μm的最低LETd,表明这种联合方法可能带来益处。大多数剂量验证显示,无论是逐束剂量还是总剂量,与TPS的剂量偏差在5%范围内。与基于标准RBE的计划(<1.5%)相比,LETd优化和SHArc计划表现出略高的平均剂量偏差(2.0%-4.6%)。
本研究证明了使用碳离子弧形投照结合LETd优化来增强胰腺肿瘤中LETd的可行性。通过对拟人化胰腺体模进行照射验证了实施这些计划的可能性,照射结果显示剂量测量与预测结果相符。