Investigating LETd optimization strategies in carbon ion radiotherapy for pancreatic cancer: a dosimetric study using an anthropomorphic phantom.

Abstract

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-SFOPhys, 2-SFORBE and 2-MFORBE-LETopt), a three-beam configuration (3-MFORBE and 3-MFORBE-LETopt) and SHArc (SHArcPhys, SHArcRBE and SHArcRBE-LETopt) 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 91keV/µm. For the pancreas-shaped volume, however, the 3-MFORBE-LETopt achieved a higher minimum LETd in the GTV than SHArcRBE (75.6 and 62.3keV/µm, respectively). When combining SHArc with LETd optimization, a minimum LETd of 76.3keV/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.