A Randomized, Phase II Clinical Trial of FLT-PET and FDG-PET for Early Response Assessment of Neoadjuvant Systemic...

Early identification of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC) can facilitate timely treatment adjustments. This phase II analytic and clinical validity study (TNPET01) evaluated whether [18F]-fluorodeoxyglucose (FDG) or [18F]-fluorothymidine (FLT) positron emission tomography (PET)/CT can predict response after one NACT cycle.

In part A (analytic validity phase), patients with stage II-III TNBC were randomized to FDG or FLT imaging. Baseline repeat scans assessed test-retest repeatability, followed by a post-cycle 1 scan in week 3. Dynamic imaging preceded static acquisitions at 90-, 120-, and 180-minute (FDG) or 90-minute (FLT), evaluating SUVmax, SUVmean, SUVpeak, and SULpeak. Tracer selection for part B was based on prespecified repeatability and response criteria. Part B (clinical validity phase) examined associations between changes in SUV (ΔSUV) after one cycle and post-cycle 3 MRI, end-of-treatment MRI, and residual cancer burden (RCB) at surgery. Exploratory analyses assessed relationships between PET response, Ki-67, and tumor-infiltrating lymphocytes (TIL).

Twenty-two patients were enrolled. Both tracers met repeatability thresholds; FDG was selected for part B owing to superior image quality and availability. Fourteen patients underwent FDG-PET across both parts. Reductions in SUVmax/mean after one cycle significantly correlated with mid-treatment MRI response and final RCB score (P < 0.005). Early post-cycle 1 increases in TILs correlated with greater metabolic reduction and lower RCB, whereas Ki-67 changes were not predictive.

FDG-PET after one NACT cycle was associated with histologic response and stronger correlations with RCB than MRI. These findings support PET as an early biomarker for treatment response and warrant validation in larger, immunotherapy-era trials.