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

Abstract

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). 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 (SUV_max) 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. 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 SUV_max 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 SUV_max 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 SUV_max 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 SUV_max was the only independent predictor of treatment response (Odds ratios, 12.42; 95% CI: 2.08, 74.15; p = 0.006). 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 SUV_max is a promising imaging biomarker for selecting patients likely to benefit from chemo-immunotherapy. 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.