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Clinical Studies

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

British Journal of Cancer volume 131, pages 709–717 (2024)Cite this article

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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 (SUVmax, 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.

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Fig. 1: Comparison of complete response rates among patient subgroups delineated by optimal PET/CT parameter cut-offs.
Fig. 2: Overall survival of patients based on optimal PET/CT parameter cut-off values.
Fig. 3: Correlation between baseline PET/CT parameters and immune cell infiltration in the tumour microenvironment using multiplex immunofluorescence staining.
Fig. 4: Radiological and multiplex immunohistochemical images of two representative patients achieving complete response in TLG-low and TLG-high subgroups.
Fig. 5: Correlation between TLG and immune-related tumour microenvironment based on RNA-seq analysis.

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Data availability

Individual data will be made available following publication upon reasonable request from the corresponding author.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 82373214), Beijing Xisike Clinical Oncology Research Foundation (Y-MSDZD2022-0878), and the Natural Science Foundation of Guangdong Province (2022A1515012483). We thank all participating patients, investigators, research staff, and members of the Independent Data Monitoring Committee.

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Author notes

  1. These authors contributed equally: Ruixi Wang, Shiliang Liu, Baoqing Chen, Qiaoqiao Li.

  2. These authors jointly supervised this work: Yingying Hu, Mian Xi.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Esophageal Cancer Institute, Guangzhou, China

    Ruixi Wang, Shiliang Liu, Baoqing Chen, Qiaoqiao Li, Xingyuan Cheng, Yujia Zhu, Li Zhang, Yonghong Hu, Mengzhong Liu, Yingying Hu & Mian Xi

  2. Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

    Ruixi Wang, Shiliang Liu, Baoqing Chen, Qiaoqiao Li, Xingyuan Cheng, Yujia Zhu, Li Zhang, Yonghong Hu, Mengzhong Liu & Mian Xi

  3. Department of Nuclear Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China

    Yingying Hu

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Contributions

Conception and design: YYH and MX; supply of study materials or patients: QQL, YJZ, MZL, YYH, and MX; gathering and compilation of data: RXW, SLL, BQC, QQL, XYC, YYH, and MX; Data analysis and interpretation: RXW, SLL, BQC, QQL, YYH, and MX; manuscript drafting and revision: all authors; approval of final version of submitted manuscript: all authors.

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Correspondence to Mian Xi.

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Wang, R., Liu, S., Chen, B. et al. 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. Br J Cancer 131, 709–717 (2024). https://doi.org/10.1038/s41416-024-02779-4

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