Analysis of the Measured FDG Uptake from the First-in-Human Clinical Trial of Biology-Guided Radiotherapy

Abstract

The RefleXion X1 system is a novel linear accelerator equipped with dual 90° PET arcs incorporated into its architecture to capture emissions from tumors and designed to respond by directing the radiation beam towards target. This study reports on the measured FDG uptake from the first in human multi-institutional clinical trial (BIOGUIDE-X) evaluating the performance and safety of the RefleXion X1 PET-LINAC. A total of nine patients treated with stereotactic body radiotherapy (SBRT) for lung (5) and bone (4) tumors were enrolled in the Cohort II of this study after screening their pre-study diagnostic PET/CT, acquired up to 60 days prior to enrollment, to ensure their tumor size between 2 to 5 cm and SUVmax >6. After CT simulation, the tumor and OARs were delineated, and patients had a 4-pass Imaging-only (BgRT Modeling) PET/CT acquisition on the X1 system to generate biology-guided radiotherapy (BgRT) plans. Before the patients' first and last SBRT fractions, they were injected with FDG, and short PET pre-scan (1-pass) was performed on the X1 followed by a long-PET acquisition (4-pass) to emulate the expected BgRT dose distribution without firing beam. Patients were also imaged on a third-party diagnostic PET/CT scanner after the last-fraction X1 scan. This study compares the SUVmax from the screening PET/CT, X1 Imaging-only scan, X1 PET pre-scan and long scan before the first and last-fractions, and final diagnostic PET/CT. The median time from injection to PET imaging was 84 ± 15.4 mins for X1 Imaging-only (used for generating BgRT plans), 77 ± 21.6 mins for X1 pre-scan (safety check before treatment start), 108+/- 22 mins for X1 long-PET (used to emulate treatment delivery), and 161 ± 23 mins for final diagnostic PET. For a nominal 10 mCi injection, the mean SUVmax for screening imaging performed on the diagnostic PET/CT was 10.8 ± 4.3. For a 15 mCi nominal injection, the mean SUVmax calculated on the X1 was 5.3 ± 2.6, 5.4 ± 2.0, 5.5 ± 2.6, 5.2 ± 1.8 and 5.4 ± 2.2 for the Imaging-only, first-fraction PET pre-scan, first-fraction long PET scan, last-fraction PET pre-scan, and last-fraction long PET scan, respectively. The overall median SUVmax for all patients across all timepoints and scans with X1 was calculated to be 4.8 with a range of 2.4 to 9.8. The median SUVmax for the diagnostic PET/CT scan after the last fraction X1 scan was 15.8 with a range of 8.5 to 27.7. The dual PET arcs and limited axial extent of the X1 PET subsystem results in lower system sensitivity in comparison to diagnostic PET scanners equipped with full ring and larger axial extent, as expected. With the same FDG injection, the RefleXion X1 produced SUVmax values that were 30.4 % of the diagnostic PET/CT scanners' values. Nevertheless, the X1 collected sufficient emission data to enable successful completion of emulated BgRT deliveries that met dose accuracy criteria in a clinical setting.