Secondary Malignancy Risk Following Proton vs. X-ray Radiotherapy of Thymic Epithelial Tumors: A Comparative Modeling Study of Thoracic Organ-Specific Cancer Risk

SIMPLE SUMMARY: Proton beam radiotherapy (PBT) offers the possibility to significantly reduce dose to surrounding organs at risk due to their physical advantages compared to X-ray based techniques. The aim of this analysis was to demonstrate whether PBT reduces secondary malignancy risks in patients with thymic malignancies compared to 3D conformal and intensity-modulated radiotherapy with photons. By using two different mechanistic calculation models we could demonstrate significant reductions of secondary malignancy risks with the use of PBT for all independent thoracic organs analyzed with the exception of the thyroid gland. This technology-driven improvement might translate into clinically relevant benefits for patients with thymic malignancies. ABSTRACT: Background: Proton beam radiotherapy (PBT) offers physical dose advantages that might reduce the risk for secondary malignancies (SM). The aim of the current study is to calculate the risk for SM after X-ray-based 3D conformal (3DCRT) radiotherapy, intensity-modulated radiotherapy (IMRT), and active pencil beam scanned proton therapy (PBS) in patients treated for thymic malignancies. Methods: Comparative treatment plans for each of the different treatment modalities were generated for 17 patients. The risk for radiation-induced SM was estimated using two distinct prediction models—the Dasu and the Schneider model. Results: The total and fatal SM risks estimated using the Dasu model demonstrated significant reductions with the use of PBS relative to both 3DCRT and IMRT for all independent thoracic organs analyzed with the exception of the thyroid gland (p ≤ 0.001). SM rates per 10,000 patients per year per Gy evaluated using the Schneider model also resulted in significant reductions with the use of PBS relative to 3DCRT and IMRT for the lungs, breasts, and esophagus (p ≤ 0.001). Conclusions: PBS achieved superior sparing of relevant OARs compared to 3DCRT and IMRT, leading to a lower risk for radiation-induced SM. PBS should therefore be considered in patients diagnosed with thymic malignancies, particularly young female patients.