AI Article Synopsis

  • A phase II trial showed that combining toripalimab (an anti-PD-1 antibody) with chemoradiotherapy is promising for treating locally advanced esophageal squamous cell carcinoma (ESCC), emphasizing the need for biomarkers to identify suitable patients.
  • In an analysis of 37 patients, high baseline PET/CT parameters, specifically SUV and TLG, correlated with lower treatment response and overall survival, while also indicating an immunosuppressive tumor microenvironment (TME).
  • The study suggests that monitoring these PET/CT metrics could help predict treatment outcomes and encourage further investigation into the relationship between metabolic activity and immune cell infiltration in ESCC.

Article 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, SUV, SUV, 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 SUV (≥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 SUV and TLG were associated with a significantly worse progression-free survival. A trend towards an inverse correlation was observed between SUV 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 SUV 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333745PMC
http://dx.doi.org/10.1038/s41416-024-02779-4DOI Listing

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