Robustness of Biology-Guided Radiotherapy Delivery to PET Biodistribution Changes within Target

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<h3>Purpose/Objective(s)</h3> Biology-guided radiotherapy (BgRT) is a novel tracked dose delivery modality that uses positron emission tomography (PET) emissions to deliver hypofractionated planned fluence to the target. This study evaluated PET biodistribution changes within target during BgRT delivery. <h3>Materials/Methods</h3> Two phantom experiments were designed to evaluate the FDG signal variations and dosimetric effects under stationary target and moving target on a non-clinical investigational radiotherapy system. For the stationary case, a custom built cylindrical 4-D detector phantom insert with a spherical target of 22 mm in diameter containing 4 quadrants that can be filled independently was used to mimic homogenous and non-homogenous FDG uptake conditions. A C-shape insert was used as a PET avid OAR. For simulating PET signal loss within tumor: BgRT plan was created for the spherical target with all quadrants filled and the plan was delivered when ¾ volume of the target was PET-avid. For the PET signal gain within tumor scenario: BgRT plan was created for the same spherical CTV structure where ¾ volume of the target was filled with FDG, mimicking non-homogeneous uptake, and delivered to a full volume PET-avid target. The dosimetric accuracy of BgRT delivery was evaluated using 3%/3 mm Gamma criterion using 4-D detector measurements. Target biodistribution changes under motion was evaluated by creating a BgRT plan with an FDG filled 26 mm diameter spherical target as a CTV and C-shape OAR moving independently (target:3D respiratory, OAR: sinusoidal motions) within a large water filled phantom. During BgRT delivery the PET avid target insert was switched to a smaller 22 mm spherical insert, simulating 40% uniform PET distribution reduction within 26mm CTV. For the moving target experiment, BgRT delivered dose was evaluated using the radiographic film under the condition of CTV coverage ≥97% and maximum dose ≤130%. For all the experiments, the target and the C-shaped OAR were filled with FDG at a ratio of 8:1 with respect to the water background mimicking normal tissue uptake, and a 5 mm CTV to PTV expansion to be targeted with a prescription of 50Gy in 5 fractions. <h3>Results</h3> For the stationary scenarios, BgRT delivery at remissive and progressive conditions achieved gamma pass-rate of 93.2 and 97.7%, respectively. The CTV coverage goals for the motion experiment were met where the minimum CTV dose was 103.3% and the maximum dose was 123.8%. <h3>Conclusion</h3> This study evaluated the biodistribution changes within CTV from planning to delivery suggesting the BgRT delivery is robust with respect to daily variations of PET signal within the PTV under these experimental conditions. Clinical feasibility of BgRT needs further evaluation.