Abstract
BACKGROUND: Tumor invasion risk (TIR) is an important prognostic factor in nasopharyngeal carcinoma (NPC). We propose a novel prognostic analytic method for NPC based on a voxelwise analysis of TIR in a coordinate system of the nasopharynx. METHODS: A stable nasopharynx coordinate system was constructed based on anatomical landmarks to obtain an accurate TIR profile for NPC. The coordinate system was validated by image registration of the lateral pterygoid muscle (LPM). The tumors were registered to the coordinate system through shift, scale, and rotation transformations. The voxelwise TIR map for NPC was obtained by superposition of all registered and mirrored tumor regions of interest. The minimum risk (MinR) point of the tumor region was used as an independent prognostic factor for NPC. The cutoff value was calculated with density plot and validated with restricted cubic splines (RCSs), and then the patients were divided into 2 groups for overall survival (OS) analysis. RESULTS: The first voxelwise TIR map of NPC was obtained based on 778 patients. The OS of patients with a low TIR was 76.8% and was 92.6% for patients with a high TIR [P<0.001; hazard ratio (HR) =1/0.45; 95% CI: 0.27-0.77; adjusted P=0.004]. Thus, patients with a low TIR had a poor prognosis, whereas patients with a high TIR had a good prognosis. The MinR may be better at grading the prognosis of patients compared to the American Joint Committee on Cancer (AJCC) staging or tumor/node (T/N) classification systems. CONCLUSIONS: The voxelwise TIR map provides a new method for the prognostic analysis of NPC. Potential clinical applications of voxelwise TIR mapping are clinical target volume (CTV) delineation and dose-painting for NPC.