Comparison of pre-treatment 68Ga-DOTA-WL12 and 18F-FDG uptake in predicting response to chemo-immunotherapy in head and neck squamous cell carcinoma.

OBJECTIVE: To investigate the value of 68Ga-DOTA-WL12 PET/CT in predicting programmed death-ligand 1 (PD-L1) expression and chemo-immunotherapy response in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This prospective study enrolled participants with histologically confirmed HNSCC who underwent both 68Ga-DOTA-WL12 and 18F-FDG PET/CT. PD-L1 expression was evaluated by immunohistochemistry; lesion-based analysis compared maximum standard uptake value (SUVmax) of both tracers between PD-L1-positive and -negative lesions. Patients receiving chemo-immunotherapy with available follow-up were included in the patient-based analysis for treatment response. Nonparametric tests, DeLong test, and multivariable logistic regression were employed. RESULTS: Thirty-four participants(median age, 59 years [range, 32-82 years]; 26 men) were enrolled. In the lesion-based analysis (37 lesions from 34 patients), 68Ga-DOTA-WL12 SUVmax was significantly higher in PD-L1-positive than -negative lesions (2.7 vs 1.7, p < 0.001), whereas 18F-FDG uptake did not differ. For identifying PD-L1 positivity, the AUC for SUVmax of 68Ga-DOTA-WL12 was significantly higher than that of 18F-FDG (0.92 vs 0.69, p = 0.003). Of these participants, 17 received chemo-immunotherapy with complete follow-up and were included in the treatment response analysis. 68Ga-DOTA-WL12 SUVmax was significantly higher in responders than non-responders (2.7 vs 1.3, p = 0.002), while 18F-FDG metrics were not discriminatory. 68Ga-DOTA-WL12 SUVmax was the only independent predictor of treatment response (Odds ratios, 12.42; 95% CI: 2.08, 74.15; p = 0.006). CONCLUSION: 68Ga-DOTA-WL12 PET/CT outperforms 18F-FDG PET/CT in assessing PD-L1 expression and predicting chemo-immunotherapy response in HNSCC. 68Ga-DOTA-WL12 SUVmax is a promising imaging biomarker for selecting patients likely to benefit from chemo-immunotherapy. KEY POINTS: Question Whether 68Ga-DOTA-WL12 PET/CT can non-invasively predict PD-L1 expression and chemo-immunotherapy response in patients with HNSCC remains unclear. Findings 68Ga-DOTA-WL12 PET/CT was superior to 18F-FDG PET/CT in identifying PD-L1-positive lesions and independently predicting response to chemo-immunotherapy in HNSCC. Clinical relevance Pre-treatment 68Ga-DOTA-WL12 PET/CT helps identify PD-L1-positive lesions and predict chemo-immunotherapy response, providing an imaging biomarker and supporting stratification for patients with HNSCC.