Feasibility of Using FDG in the Stereotactic Ablative Setting for Tracked Dose Delivery With BgRT: Results from a Prospective Study of Serial Inter-Fraction PET/CTs


      Biology-guided radiotherapy (BgRT) is a new radiation modality that utilizes real-time limited time sampled FDG PET images of a tumor to deliver a dynamically tracked dose distribution. Since the delivered radiotherapy dose is dependent on the FDG distribution at each fraction, the ability to deliver the planned dose despite variations in daily FDG signal must be established. This study evaluates the predicted dose distribution for BgRT based on serial FDG scans obtained over a course of stereotactic ablative radiotherapy (SABR).


      Six patients with 1 (n = 5) or 2 (n = 1) lung tumors at least 2 cm in diameter with SUVmax ≥ 6 treated with SABR (50 Gy in 5 fractions) were selected for this investigation. These patients received 3 PET/CT scans as part of an IRB approved prospective clinical trial: within 2 weeks of treatment start (PET1), between fractions 1 and 2 (PET2), and between fractions 4 and 5 (PET3). A simulation tool was developed to convert PET1 into a simulated BgRT planning PET image accounting for differences in system sensitivity, acquisition time, reconstruction method and geometry between the diagnostic PET/CT system and the BgRT machine. This same tool was used to convert PET2 and PET3 into simulated pre-scan PET images, short PET acquisitions made just prior to a BgRT delivery fraction to ensure the current FDG distribution is safe for treatment. BgRT plans designed to deliver 50 Gy in 5 fractions following RTOG 0813 dose constraints were developed for each of the 7 targets using the simulated planning PET images as input. Expected variations in the dynamically calculated dose delivery are presented as bounds on the dose-volume histogram (DVH). For each plan, the predicted DVH for fractions 2 and 5 was calculated from the simulated pre-scan PET images and compared to the bounded DVH of the BgRT plan. The pass %, defined as the percentage of points on the predicted DVH curves falling within the planned DVH bounds, was automatically calculated; the pass % must be ≥ 95% to proceed with BgRT delivery.


      All 7 BgRT plans met target coverage objectives and normal tissue constraints. The mean pass % for the 14 pre-scans was 98.6%, with 13 exceeding the 95% threshold required for BgRT. There was no statistically significant difference between pass % at fraction 2 versus fraction 5 (two-tailed paired t-test, P = 0.44). The pass % was 92.2% for 1 pre-scan. In this case, the target SUVmax had decreased by 55.5% of the baseline value.


      This investigation provides initial evidence that FDG scans remain stable enough over a course of ablative radiotherapy to enable dynamically tracked dose delivery with BgRT. Significant changes in FDG biodistribution that would prevent dose from being delivered within the pre-approved bounds of the BgRT plan can be identified through analysis of a pre-scan PET image. A prospective clinical trial to confirm these results is in preparation. Clinical trial number NCT03493789.
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