Abstract Purpose Tebentafusp has emerged as the first systemic therapy to significantly prolong survival in treatment-naïve HLA-A*02:01 + patients with unresectable or metastatic uveal melanoma (mUM). Notably, a survival benefit has been observed even in the absence of radiographic response. This study aims to investigate the feasibility and prognostic value of artificial intelligence (AI)-assisted quantification and metabolic response assessment of 18 FFDG long axial field-of-view (LAFOV) PET/CT in mUM patients undergoing tebentafusp therapy. Materials and methods Fifteen patients with mUM treated with tebentafusp underwent 18 FFDG LAFOV PET/CT at baseline and 3 months post-treatment. Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were quantified using a deep learning-based segmentation tool On the RECOMIA platform. Metabolic response was assessed according to AI-assisted PERCIST 1.0 criteria. Associations between PET-derived parameters and overall survival (OS) were evaluated using Kaplan–Meier survival analysis. Results The median follow up (95% CI) was 14.1 months (12.9 months – not available). Automated TMTV and TLG measurements were successfully obtained in all patients. Elevated baseline TMTV and TLG were significantly associated with shorter OS (TMTV: 16.9 vs. 27.2 months; TLG: 16.9 vs. 27.2 months; p < 0.05). Similarly, higher TMTV and TLG at 3 months post-treatment predicted poorer survival outcomes (TMTV: 14.3 vs. 24.5 months; TLG: 14.3 vs. 24.5 months; p < 0.05). AI-assisted PERCIST response evaluation identified six patients with disease control (complete metabolic response, partial metabolic response, stable metabolic disease) and nine with progressive metabolic disease. A trend toward improved OS was observed in patients with disease control (24.5 vs. 14.6 months, p = 0.08). Circulating tumor DNA (ctDNA) levels based on GNAQ and GNA11 mutations were available in 8 patients; after 3 months Of tebentafusp treatment, 5 showed reduced Or stable ctDNA levels, and 3 showed an increase (median OS: 24.5 vs. 3.3 months; p = 0.13). Patients with increasing ctDNA levels exhibited significantly higher TMTV and TLG on follow-up imaging. Conclusion AI-assisted whole-body quantification of 1⁸FFDG PET/CT and PERCIST-based response assessment are feasible and hold prognostic significance in tebentafusp-treated mUM. TMTV and TLG may serve as non-invasive imaging biomarkers for risk stratification and treatment monitoring in this malignancy.
Sachpekidis et al. (Sat,) studied this question.