Physical Validation of Biology-Guided Radiotherapy for Delivering a Tracked Dose Distribution to a Moving PET-Avid Target

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Biology-guided radiotherapy (BgRT) integrates PET detectors with a LINAC and delivers a real-time tracked dose of radiation to moving targets using a continuous stream of limited time-sampled (LTS) PET images as a biological fiducial. These LTS PET images are converted into fluences and delivered to the target that cumulatively sum to deliver the intended prescription dose to the planning target volume (PTV). Physical validation of BgRT directed at a moving target has not previously been reported.An 18F-Fluorodeoxyglucose (FDG) fillable insert that fits inside the independent quality assurance tool cavity was used in these experiments. The insert included a 22mm diameter target enclosed within a Styrofoam mesh compartment, simulating a lung-like background. The insert was filled with FDG with a target-to-background ratio of 8:1, placed in the independent quality assurance tool cavity which was then mounted on a custom motion stage that could move in the axial direction (IEC-Y). Motion was simulated using a breathing waveform that had a large amplitude motion (from -14.3 mm to +14.4 mm with respect to the mean position), with random amplitude and period with a baseline shift over time, simulating breathing baseline shifts. A BgRT plan (prescription of 8Gy) was created using motion averaged PET images, acquired on a pre-commercial version of the RefleXion system using a 32 × 32 × 32mm (IEC-X, Y, Z) PTV - 5mm expansion over the clinical target volume (CTV). An internal tumor volume (ITV) based SBRT plan (prescription of 10Gy) with a 32 × 32 × 62mm PTV covering the motion extent was also created. Radiochromic EBT-XD film was inserted into a slot in the spherical target to measure the delivered dose. Using the same motion waveform, BgRT and SBRT plans were delivered to the moving target, with an additional 8Gy BgRT delivery (32 × 32 × 32mm PTV) to the stationary target serving as control. Dosimetric accuracy for moving targets was measured using the concept of coverage where 100% of the CTV receives at least 97% of the prescription dose and maximum dose in the CTV was = < 130% of the maximum planned dose.Under motion, both SBRT (32 × 32 × 62mm PTV) and BgRT (32 × 32 × 32mm PTV) met CTV dose coverage. CTV dose ranges were a) Motion SBRT: measured = [10.4Gy,12.4Gy], plan = [9.7Gy, 17.2Gy], b) Motion BgRT: measured = [9.7Gy,11.2Gy], plan = [7.8Gy, 15.3Gy], c) Static BgRT: measured = [8.7Gy,10.1Gy], plan = [7.8Gy), 10.4Gy]. Motion coverage results indicate that BgRT with a PTV that is 48.4% smaller than the SBRT PTV, delivering a tracked dose to the moving target., indicating a more conformal delivery.This is the first report of BgRT delivery achieving a tracked dose distribution directed at a moving target. Because tracked distributions have better conformality and normal tissue sparing than free-breathing internal tumor volume approaches, BgRT may improve the toxic-therapeutic ratio for applications such as early-stage lung cancer.