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

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).

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(RBE_1.1)) and 20% (13.6 Gy(RBE_1.1)) dose escalation to the BTV with protons and compared results with proton plans without dose escalation.

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.

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.