1. Prognostic significance of PET/CT and its association with immuno-genomic profiling in oesophageal squamous cell carcinoma treated with immunotherapy plus chemoradiotherapy: results from a phase II study.
- Author
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Wang R, Liu S, Chen B, Li Q, Cheng X, Zhu Y, Zhang L, Hu Y, Liu M, Hu Y, and Xi M
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Prognosis, Antibodies, Monoclonal, Humanized therapeutic use, Adult, Positron Emission Tomography Computed Tomography methods, Esophageal Squamous Cell Carcinoma therapy, Esophageal Squamous Cell Carcinoma genetics, Esophageal Squamous Cell Carcinoma immunology, Esophageal Squamous Cell Carcinoma diagnostic imaging, Esophageal Squamous Cell Carcinoma pathology, Chemoradiotherapy methods, Esophageal Neoplasms therapy, Esophageal Neoplasms genetics, Esophageal Neoplasms pathology, Esophageal Neoplasms immunology, Immunotherapy methods, Tumor Microenvironment
- Abstract
Background: A phase II trial (EC-CRT-001) demonstrated the promising efficacy of combining toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) for locally advanced oesophageal squamous cell carcinoma (ESCC). Biomarkers are key to identifying patients who may benefit from this therapeutic approach., Methods: Of the 42 patients with ESCC who received toripalimab combined with definitive CRT, 37 were included in this analysis. Baseline assessments included PET/CT metabolic parameters (SUV
max , SUVmean , SUVpeak , MTV, and TLG), RNA sequencing of tumour biopsies to quantify the tissue mutational burden (TMB), and multiplex immunofluorescence staining to estimate immune cell infiltration in the tumour microenvironment (TME). Frozen neoplastic samples were procured for RNA sequencing to further explore the immune-related TME., Results: Among the 37 patients, high baseline SUVmax (≥12.0; OR = 6.5, 95% CI 1.4-48.2, p = 0.032) and TLG (≥121.8; OR = 6.8, 95% CI 1.6-33.5, p = 0.012) were significantly correlated with lower complete response rates. All five PET/CT parameters were notably associated with overall survival; only SUVmax and TLG were associated with a significantly worse progression-free survival. A trend towards an inverse correlation was observed between SUVmax and TMB (R = -0.33, p = 0.062). PD-1 + CD8 + T cell infiltration was negatively correlated with MTV (R = -0.355, p = 0.034) and TLG (R = -0.385, p = 0.021). Moreover, RNA sequencing revealed that the high TLG subgroup exhibited low immune cell infiltration, indicating an immunosuppressive landscape., Conclusions: High baseline SUVmax and TLG might predict poorer treatment response and worse survival in patients with ESCC undergoing immunotherapy combined with CRT. In addition, high PET/CT metabolic parameters, particularly TLG, were correlated with an immunosuppressive TME, which warrants further exploration., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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