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Purpose <p>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 [<sup>18</sup>F]FDG long axial field-of-view (LAFOV) PET/CT in mUM patients undergoing tebentafusp therapy.</p> Materials and methods <p>Fifteen patients with mUM treated with tebentafusp underwent [<sup>18</sup>F]FDG LAFOV PET/CT at baseline and 3&#xa0;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.</p> Results <p>The median follow up (95% CI) was 14.1&#xa0;months (12.9&#xa0;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&#xa0;months; TLG: 16.9 vs. 27.2&#xa0;months; <i>p</i> &lt; 0.05). Similarly, higher TMTV and TLG at 3&#xa0;months post-treatment predicted poorer survival outcomes (TMTV: 14.3 vs. 24.5&#xa0;months; TLG: 14.3 vs. 24.5&#xa0;months; <i>p</i> &lt; 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&#xa0;months, <i>p</i> = 0.08). Circulating tumor DNA (ctDNA) levels based on GNAQ and GNA11 mutations were available in 8 patients; after 3&#xa0;months Of tebentafusp treatment, 5 showed reduced Or stable ctDNA levels, and 3 showed an increase (median OS: 24.5 vs. 3.3&#xa0;months; <i>p</i> = 0.13). Patients with increasing ctDNA levels exhibited significantly higher TMTV and TLG on follow-up imaging.</p> Conclusion <p>AI-assisted whole-body quantification of [1⁸F]FDG 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.</p>

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Artificial intelligence-assisted assessment of metabolic response to tebentafusp in metastatic uveal melanoma: a long axial field-of-view [18F]FDG PET/CT study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月6日

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  • Christos Sachpekidis,
  • Devayani Machiraju,
  • Dimitrios Stefanos Strauss,
  • Leyun Pan,
  • Annette Kopp-Schneider,
  • Lars Edenbrandt,
  • Antonia Dimitrakopoulou-Strauss,
  • Jessica C. Hassel

摘要

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 [18F]FDG 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 [18F]FDG 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 [1⁸F]FDG 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.