Influence of 18F-sodium fluoride PET/CT on retrospective AJCC/UICC version 9–based staging assessment and radiotherapy target volumes in newly diagnosed nasopharyngeal carcinoma: a retrospective cohort study

Accurate assessment of skull-base bone involvement and skeletal metastases is essential for staging and radiotherapy planning in nasopharyngeal carcinoma (NPC). We evaluated the influence of 18 F-sodium fluoride ( 18 F-NaF) PET/CT on T- and M-category classification using retrospectively applied AJCC/UICC Version 9 criteria and target-volume delineation in newly diagnosed NPC. This single-center retrospective cohort study included 265 patients with newly diagnosed NPC who underwent pretreatment conventional imaging and 18 F-NaF PET/CT. Among the 25 patients with T-category reclassification, paired conventional-imaging-informed and 18 F-NaF PET/CT-informed gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) data were available for 11 patients. The remaining 14 patients were excluded from the target-volume analysis because technical limitations prevented reliable image registration between CT and 18 F-NaF PET/CT. Among the 183 eligible patients in the T-category-unchanged cohort, 30 were selected using a computer-generated random-number sequence for paired target-volume analysis. An exploratory 1:1 propensity score-matched analysis used age, sex, and AJCC/UICC Version 9 stage. T-category changes occurred in 25 of 265 patients (9.4%; 95% CI, 6.5%-13.6%), and M-category changes occurred in 13 of 265 patients (4.9%; 95% CI, 2.9%-8.2%) after 18 F-NaF PET/CT was added. Among the four patients with established M1 disease whose M category remained unchanged, additional 18 F-NaF-avid skeletal findings were identified in three patients. Median paired volume increases in the NaF-positive/MRI-negative cohort were 0.96, 4.50, and 6.45 cm 3 for GTVnx, CTV, and PTV, respectively; the corresponding increases in the NaF-positive/MRI-positive cohort were 3.80, 1.75, and 0.05 cm 3 . In the exploratory matched analysis of 11 pairs, relative CTV and PTV changes were numerically larger in the T-category-changed cohort than in the T-category-unchanged cohort; however, residual covariate imbalance persisted after matching, limiting the interpretation of these findings. Adding 18 F-NaF PET/CT to conventional imaging was associated with T- or M-category reclassification in a minority of patients and altered target-volume contours in selected cases. These findings should be interpreted as imaging-based stage reclassification, while the effect of 18 F-NaF PET/CT on staging accuracy requires further validation against an independent reference standard. Given the retrospective single-center design, small contouring cohort, and residual imbalance after matching, prospective validation against an independent reference standard is needed before routine clinical adoption.