A Pilot Study of Simulation-Free Hippocampal-Avoidance Whole Brain Radiotherapy Using Diagnostic MR-Based and Online Adaptive Planning

Abstract

We aimed to demonstrate the clinical feasibility and safety of a simulation-free hippocampal avoidance whole brain radiotherapy (HA-WBRT) workflow in a Phase I clinical trial (NCT05096286). Feasibility was defined as successful completion of the simulation-free HA-WBRT workflow through treatment delivery in at last 70% of treated patients. Ten candidates for HA-WBRT were enrolled for treatment on a ring gantry CT-guided Linac with online adaptive capabilities. Structures were contoured on the diagnostic brain MRI, which was then registered to a separate head computed tomography (CT) of similar head shape, obtained from an atlas-based database. A HA-WBRT "pre-plan" was generated using the atlas-based CT (AB-CT) and the NRG-CC001 constraints. At first fraction, the AB-CT was used as the primary dataset and deformed to the patient's cone-beam CT (CBCT) for dose calculation. The brain, ventricles, and brainstem contours were matched through rigid translation and rotation to the corresponding anatomy on the CBCT to aid in alignment, given the differences in rotational head positioning from diagnostic MRI to CBCT setup. Lastly, the lens, optic nerves, and brain contours were manually edited based on CBCT visualization. Plans were then optimized, and the adaptive plan was chosen for treatment if the plan met all objectives. Workflow tasks were timed. In addition, conventional plans using patients' sim CTs were created for each patient for the purpose of prospective dosimetric comparison. The dosimetric parameters were compared for each patient between the delivered sim-free plan and the conventional sim CT plan using the sign test via statistical software, with p<.05 indicating significance. Median time from approved sim order to first fraction was 4 days (range: 2-7); median time in room (door-to-door) was 49 minutes (range: 35-70). All patients successfully completed all ten fractions and 90% of the simulation-free radiation plans met all NRG-CC001 constraints. For one patient, the sim-free plan at fraction one failed the planning target volume (PTV) coverage objective (coverage of 89%); this was deemed acceptable for delivery by the treating radiation oncologist. An offline replan was then performed to meet NRG-CC001 constraints and used for the subsequent nine fractions. There was no clinically meaningful difference in dosimetric constraints between the sim-free plan (calculated on AB-CT) and conventional CT sim plan. Statistically, the sim-free plans provided improved PTV coverage to higher doses compared to the conventional plans (Table). At a median follow-up of 43 days (range: 9 -280), the intracranial progression-free survival rate was 90%. Simulation-free HA-WBRT is feasible, results in plans that are dosimetrically comparable to conventional CT sim workflows and succeeds in decreasing time to initiation of HA-WBRT by at least 50%. Further studies with a larger cohort are warranted to optimize the workflow.