Abstract: Pencil beam scanning (PBS) proton therapy provide highly conformal tumor coverage, while sparing adjacent organs-at-risk due to its unique physics characteristics, i.e., Bragg peak. But it also introduces additional complexities since proton deposits most of the energy within a short distance, resulting in high linear energy transfer (LET) compared to traditional photon therapy. Therefore, its relative biologically effective (RBE) dose may vary significantly even for the same delivered physical dose. However, clinical use of LET is limited because of the uncertainties and discrepancies in RBE modelling and calculation. Thus, current IMPT plan evaluation exclusively relies on physical dose and ignores critical LET information, resulting in unanticipated adverse events (AEs).

Recently we have performed the LET-related AE studies in both prostate cancer (focusing on rectal bleeding) and head and neck cancer (focusing on osteoradionecrosis) patients treated by PBS via a novel tool of dose-LET volume histogram (DLVH) to visualize dose, LET, and the structure volume in one plot. While avoiding the need for exact RBE calculation, we have correlated AEs with accurate physical quantities of dose and LET to establish dose-LET volume constraints (DLVCs) and the normal tissue complication probability model has been established based on the derived DLVCs in prostate cancer for rectal bleeding. In addition, we have performed a large-scale (1,266 patients) retrospective, case-matched cohort study to investigate empirical relative biological effectiveness (RBE) for mandible osteoradionecrosis in head and neck cancer patients treated with PBS. RBE larger than 1.1 was observed at moderate doses in PBS for mandible osteoradionecrosis. We have further developed empirical dose-LET biological effect models of AEs via the seed spot analysis facilitated by the contoured AE sites to study the LET-enhancing effects in head and neck cancer. The results have been integrated into our GPU-accelerated and Monte Carlo-based in-house developed treatment planning system (TPS), Shiva, for routine clinical use.  Some DEMOs of this TPS will be given to show the clinical translation of our results.

About the Speaker: Dr. Wei Liu is Professor of Radiation Oncology of Mayo College of Medicine and Science and Research Director of Division of Medical Physics of Mayo Clinic in Arizona. He was the recipients of the President’s Discovery Translational Program Award of Mayo Clinic in 2022, the John S. Laughlin Young Scientist Award of American Association of Physicists in Medicine (AAPM) in 2019, the Arizona State Department of Health Sciences Investigator Award in 2017, and the NIH/NCI Early Career Award (K25) in 2012. Dr. Liu has 90 (43 are corresponding or first authored) peer-reviewed journal publications, 7 US patents, 2 European patent, 15 disclosures, and 2 book chapters. One of his disclosures has been licensed. A leading radiotherapy company, Varian Medical Systems, has adopted methods he developed as the basis for its commercial treatment planning solutions. A scientific term Liu Limit was named after him for his work in plasma astrophysics. He is an Associate Editor of Med. Phys. and an Editorial Board member of Phys. Med. Biol. He currently serves in the Imaging Technology Development (ITD) study section of NIH and as a reviewer for The Netherlands Organisation for Scientific Research (NWO/ZonMw).