Individualized Radiosensitivity-Guided Radiation Therapy for Cervical Cancer
Abstract
Purpose
Concurrent chemoradiotherapy combined with image-guided brachytherapy is the standard for locally advanced cervical cancer, yet failures persist due to heterogeneous radioresistant sub-volumes. While Dose Painting by Numbers (DPbN) enables voxel-level modulation, current strategies often ignore temporal biological evolution. We propose a voxel-level Biologically-guided Adaptive Radiotherapy (BgART) framework using sequential PET/CT to guide patient-specific dose prescriptions.
Methods
We retrospectively analyzed 18 patients treated with radical IMRT. Sequential 18F-FDG PET/CT scans were acquired at baseline and mid-treatment. Using in-house developed software and deformable image registration, we extracted voxel-level metabolic kinetics to construct a Dose Response Matrix (DRM), mapping SUV changes to the surviving fraction (SF2). In the feature space of (SUV0, DRM), a boundary curve distinguishing controlled from uncontrolled voxels was fitted. Subsequently, a dose-Tumor Voxel Control Probability (TVCP) model was established using maximum likelihood estimation. Finally, a voxel-wise prescription function was inversely derived to calculate the minimum dose required for target control.
Results
Model-predicted TCP showed high concordance with 3-month clinical outcomes (AUC=0.86). Under a uniform reference dose of 56 Gy, predicted TCP varied substantially (0.27–0.89). To attain 95% TCP, calculated voxel-specific minimum doses ranged from 86.3 to 100.4 Gy, aligning closely with cumulative clinical doses (external beam plus brachytherapy). Consequently, the tumor voxel fraction controlled by standard prescriptions varied widely (41%–94%). The resulting dose maps accurately identified radioresistant "hotspots."
Conclusion
This study validates a voxel-level BgART framework that effectively translates early metabolic response into actionable dose prescriptions. By targeting intrinsic radioresistance identified via longitudinal PET/CT, this approach offers a promising strategy to individualize treatment and potentially improve local control.