A Randomized, Phase II Clinical Trial of FLT-PET and FDG-PET for Early Response Assessment of Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer.

Abstract

PURPOSE Early identification of response to neoadjuvant chemotherapy (NACT) in triple negative breast cancer (TNBC) can facilitate timely treatment adjustments. This phase II analytical and clinical validity study (TNPET01) evaluated whether [18F]-fluorodeoxyglucose (FDG) or [18F]-fluorothymidine (FLT) PET/CT can predict response after one NACT cycle Methods: In Part A (analytical validity phase), patients with stage II-III TNBC were randomised 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-min (FDG) or 90-min (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 tumour-infiltrating lymphocytes (TILs). RESULTS Twenty-two patients 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. ΔSUVmax/mean after one cycle significantly correlated with mid-treatment MRI and final RCB score (p < 0.005). Early post-cycle-1 TIL increases correlated with greater metabolic reduction and lower RCB, while Ki-67 changes were not predictive. CONCLUSIONS FDG-PET after one NACT cycle was associated with histological 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.