Interim 18F-FDG-PET based response-adaptive dose escalation of proton therapy for head and neck cancer: a treatment planning feasibility study.

BACKGROUND: Image-driven dose escalation to tumor subvolumes has been proposed to improve treatment outcome in head and neck cancer (HNC). We used 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) acquired at baseline and into treatment (interim) to identify biologic target volumes (BTVs). We assessed the feasibility of interim dose escalation to the BTV with proton therapy by simulating the effects to organs at risk (OARs). METHODS: We used the semiautomated just-enough-interaction (JEI) method to identify BTVs in 18F-FDG-PET images from nine HNC patients. Between baseline and interim FDG-PET, patients received photon radiotherapy. BTV was identified assuming that high standardized uptake value (SUV) at interim reflected tumor radioresistance. Using Eclipse (Varian Medical Systems), we simulated a 10% (6.8 Gy(RBE1.1)) and 20% (13.6 Gy(RBE1.1)) dose escalation to the BTV with protons and compared results with proton plans without dose escalation. RESULTS: At interim 18F-FDG-PET, radiotherapy resulted in reduced SUV compared to baseline. However, spatial overlap between high-SUV regions at baseline and interim allowed for BTV identification. Proton therapy planning demonstrated that dose escalation to the BTV was feasible, and except for some 20% dose escalation plans, OAR doses did not significantly increase. CONCLUSION: Our in silico analysis demonstrated the potential for interim 18F-FDG-PET response-adaptive dose escalation to the BTV with proton therapy. This approach may give more efficient treatment to HNC with radioresistant tumor subvolumes without increasing normal tissue toxicity. Studies in larger cohorts are required to determine the full potential for interim 18F-FDG-PET-guided dose escalation of proton therapy in HNC.

Hypoxia adapted relative biological effectiveness models for proton therapy: a simulation study.

In proton therapy, a constant relative biological effectiveness (RBE) factor of 1.1 is applied although the RBE has been shown to depend on factors including the Linear Energy Transfer (LET). The biological effectiveness of radiotherapy has also been shown to depend on the level of oxygenation, quantified by the oxygen enhancement ratio (OER). To estimate the biological effectiveness across different levels of oxygenation the RBE-OER-weighted dose (ROWD) can be used. To investigate the consistency between different approaches to estimate ROWD, we implemented and compared OER models in a Monte Carlo (MC) simulation tool. Five OER models were explored: Wenzl and Wilkens 2011 (WEN), Tinganelliet al2015 (TIN), Strigariet al2018 (STR), Dahleet al2020 (DAH) and Meinet al2021 (MEI). OER calculations were combined with a proton RBE model and the microdosimetric kinetic model for ROWD calculations. ROWD and OER were studied for a water phantom scenario and a head and neck cancer case using hypoxia PET data for the OER calculation. The OER and ROWD estimates from the WEN, MEI and DAH showed good agreement while STR and TIN gave higher OER values and lower ROWD. The WEN, STR and DAH showed some degree of OER-LET dependency while this was negligible for the MEI and TIN models. The ROWD for all implemented models is reduced in hypoxic regions with an OER of 1.0-2.1 in the target volume. While some variations between the models were observed, all models display a large difference in the estimated dose from hypoxic and normoxic regions. This shows the potential to increase the dose or LET in hypoxic regions or reduce the dose to normoxic regions which again could lead to normal tissue sparing. With reliable hypoxia imaging, RBE-OER weighting could become a useful tool for proton therapy plan optimization.