No abstract

Recent success of sequential administration of immunotherapy following radiotherapy (RT), often referred to as immunoRT, has sparked the urgent need for novel clinical trial designs to accommodate the unique features of immunoRT. For this purpose, we propose a Bayesian phase I/II design for immunotherapy administered after standard‐dose RT to identify the optimal dose that is personalized for each patient according to his/her measurements of PD‐L1 expression at baseline and post‐RT. We model the immune response, toxicity, and efficacy as functions of dose and patient's baseline and post‐RT PD‐L1 expression profile. We quantify the desirability of the dose using a utility function and propose a two‐stage dose‐finding algorithm to find the personalized optimal dose. Simulation studies show that our proposed design has good operating characteristics, with a high probability of identifying the personalized optimal dose.

Objective. Feasibility of three-dimensional (3D) tracking of volumetric modulated arc therapy (VMAT) based on VMAT–computed tomography (VMAT-CT) has been shown previously by our group. However, 3D VMAT-CT is not suitable for treatments that involve significant target movement due to patient breathing. The goal of this study was to reconstruct four-dimensional (4D) VMAT-CT and evaluate the feasibility of tracking based on 4D VMAT-CT. Approach. Synchronized EPID images of phantoms and linac log were both sorted into four phases, and VMAT-CT+ was generated in each phase by fusing reconstructed VMAT-CT and planning CT using rigid or deformable registration. Dose was calculated in each phase and was registered to the mean position planning CT for 4D dose reconstruction. Trackings based on 4D VMAT-CT+ and 4D cone beam CT (CBCT) were compared. Potential uncertainties were also evaluated. Main results. Tracking based on 4D VMAT-CT+ was accurate, could detect phantom deformation and/or change of breathing pattern, and was superior to that based on 4D CBCT. The impact of uncertainties on tracking was minimal. Significance. Our study shows it is feasible to accurately track position and dose based on 4D VMAT-CT for patients whose VMAT treatments are subject to respiratory motion. It will significantly increase the confidence of VMAT and is a clinically viable solution to daily patient positioning, in vivo dosimetry and treatment monitoring.