Biological uncertainties in proton therapy for paediatric mediastinal Hodgkin Lymphoma

Abstract

Purpose or Objective Proton Beam Therapy (PBT) is associated with different types of uncertainties than photon therapy. For example, it is unknown how much the increase in linear energy transfer (LET) and relative biological effectiveness (RBE) at the end of a proton’s range impact the doses to organs at risk (OARs). For paediatric patients with mediastinal Hodgkin lymphoma (HL), increased LET at the distal edge of the beam could, in theory, result in “hot spots” in the heart, oesophagus or lungs. Here, we investigate the impact of different beam arrangements on the LET distribution and dose to mediastinal OARs. In addition, we explore the impact of using a variable RBE in the dose calculation. Material and Methods Three paediatric patients with mediastinal HL previously treated with photon-based radiotherapy were selected for this study (ages 14-16 clinical stage 2A, one with bulky disease). We retrospectively created proton plans for each patient with 1 (anterior-posterior (AP)), 2 (APoblique), and 3 (AP-oblique and posterior-anterior) beams for a Varian Probeam delivery system, using a commercial treatment planning system (TPS, Eclipse v13.7). The prescription dose was 19.8 Gy (RBE) in 11 fractions. Beam arrangements were selected to reflect current clinical practice for paediatric HL treatments. Robust optimisation to the CTV, assuming an uncertainty of 3.5% in CT calibration and 5 mm in positioning was used. Single field uniform dose optimisation was used as a default and plans were optimised for a fixed RBE of 1.1. All plans were exported and recalculated with AUTOMC, an in-house Monte Carlo (MC) software based on GATE v8.1 and GEANT4 v10.3.3 (GATE RTion). Dose-averaged LET was scored and variable RBE dose was calculated using the McNamara model with an alpha/beta ratio of 2. Doses to the heart, cardiac sub-structures, lungs, breasts, oesophagus and spinal cord were recorded. A “hot spot” was defined as an overlap of regions receiving ≥ 80% prescription dose and regions with high LET (≥6 keV/μm). Results All treatment plans had acceptable target coverage and robustness (evaluated with TPS dose). Dose differences between all strategies (TPS with fixed RBE, MC with fixed RBE and MC with variable RBE) were small (see figure 1). LET generally decreased as the number of beams increased. No “hot spot” was observed in plans using > 1 field. However, 2 plans using a 1-field arrangements revealed small “hot spots“ of 0.004 cc in muscle (Patient 1), or 0.11 cc located in the vertebra, carina, and descending aorta (Patient 3). The use of MC had a larger influence on the dose distribution than the use of a variable RBE (see figure 2). Conclusion In this study, increased LET and RBE at the end of proton range did not result in clinically meaningful hot-spots to OARs for paediatric patients with mediastinal HL, regardless of the beam arrangement. However, uncertainties remain in models of variable RBE, and further studies are needed to confirm these results.