Predictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab

Baoqing Chen, Shiliang Liu, Yujia Zhu, Ruixi Wang, Xingyuan Cheng, Biqi Chen, Mihnea P. Dragomir, Yaru Zhang, Yonghong Hu, Mengzhong Liu, Qiaoqiao Li (), Hong Yang () and Mian Xi ()
Additional contact information
Baoqing Chen: Guangdong Esophageal Cancer Institute
Shiliang Liu: Guangdong Esophageal Cancer Institute
Yujia Zhu: Guangdong Esophageal Cancer Institute
Ruixi Wang: Guangdong Esophageal Cancer Institute
Xingyuan Cheng: Guangdong Esophageal Cancer Institute
Biqi Chen: Guangdong Esophageal Cancer Institute
Mihnea P. Dragomir: Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin
Yaru Zhang: Nanjing Geneseeq Technology Inc
Yonghong Hu: Guangdong Esophageal Cancer Institute
Mengzhong Liu: Guangdong Esophageal Cancer Institute
Qiaoqiao Li: Guangdong Esophageal Cancer Institute
Hong Yang: Guangdong Esophageal Cancer Institute
Mian Xi: Guangdong Esophageal Cancer Institute

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.

Date: 2024
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DOI: 10.1038/s41467-024-46307-7

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