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Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study

  • Authors:
    • Qiong He
    • Xun Shi
    • Junrong Yan
    • Mengmeng Wu
    • Cuiping Gu
    • Xinmin Yu
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China, Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu 210032, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 29
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    Published online on: February 9, 2024
       https://doi.org/10.3892/mco.2024.2727
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Abstract

Anti‑programmed cell death 1 immuno‑monotherapy has become the second‑line standard treatment for advanced esophageal squamous cell carcinoma (ESCC) after the failure of first‑line chemotherapy. However, new biomarkers are still needed to identify patients at risk of tumor progression and to select patients with advanced ESCC who are likely to benefit from immunotherapy. A total of 12 patients with advanced ESCC treated with tislelizumab were prospectively enrolled and endoscopic biopsy samples were collected. Plasma was obtained prior to and after every 2‑3 treatment cycles with tislelizumab and when disease progression occurred. Targeted sequencing of 425 genes from plasma cell‑free DNA, DNA from leukocytes and fixed esophageal tumor biopsies was performed. The patients underwent imaging analyses every 6‑8 weeks until disease progression. The association between status of circulating tumor DNA (ctDNA) or changes in ctDNA following tislelizumab immunotherapy and response, tumor progression and survival was determined. All patients had evaluable next‑generation sequencing results at the time of analysis. The results showed that patients with ESCC with liver metastasis had a significantly shorter median progression‑free survival (mPFS: 1.4 vs. 11.7 months; P=0.037). TSC complex subunit 2 [11.7 months vs. not reached (NR); P=0.004] and zinc finger protein 217 (11.7 months vs. NR; P=0.022) gene mutations were the independent and negative prognostic factors for median overall survival (OS), respectively. Of note, ctDNA dynamic changes expressed as ∆ mutant molecules per milliliter of plasma (∆MMPM; MMPM detected at the first monitoring time‑point after the first infusion of tislelizumab as baseline MMPM) predicted progression‑free survival (PFS) and OS more accurately compared to the ctDNA change of an individual gene. ∆MMPM <20% was an independent predictor of PFS (2.8 vs. 14.6 months; P=0.029), although there was no significant difference for OS (16.7 vs. 17.6 months; P=0.830). In conclusion, changes in ctDNA levels were associated with anti‑tumor effects, progression and disease‑specific survival. ctDNA sequencing is promising for predicting response and progression after tislelizumab immunotherapy as second‑line monotherapy for advanced ESCC [the present study was part of the RATIONALE‑302 study (ClinicalTrials.gov identifier no. NCT03430843; 29.01.2018)].
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Copy and paste a formatted citation
Spandidos Publications style
He Q, Shi X, Yan J, Wu M, Gu C and Yu X: Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study. Mol Clin Oncol 20: 29, 2024.
APA
He, Q., Shi, X., Yan, J., Wu, M., Gu, C., & Yu, X. (2024). Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study. Molecular and Clinical Oncology, 20, 29. https://doi.org/10.3892/mco.2024.2727
MLA
He, Q., Shi, X., Yan, J., Wu, M., Gu, C., Yu, X."Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study". Molecular and Clinical Oncology 20.4 (2024): 29.
Chicago
He, Q., Shi, X., Yan, J., Wu, M., Gu, C., Yu, X."Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study". Molecular and Clinical Oncology 20, no. 4 (2024): 29. https://doi.org/10.3892/mco.2024.2727
Copy and paste a formatted citation
x
Spandidos Publications style
He Q, Shi X, Yan J, Wu M, Gu C and Yu X: Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study. Mol Clin Oncol 20: 29, 2024.
APA
He, Q., Shi, X., Yan, J., Wu, M., Gu, C., & Yu, X. (2024). Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study. Molecular and Clinical Oncology, 20, 29. https://doi.org/10.3892/mco.2024.2727
MLA
He, Q., Shi, X., Yan, J., Wu, M., Gu, C., Yu, X."Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study". Molecular and Clinical Oncology 20.4 (2024): 29.
Chicago
He, Q., Shi, X., Yan, J., Wu, M., Gu, C., Yu, X."Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study". Molecular and Clinical Oncology 20, no. 4 (2024): 29. https://doi.org/10.3892/mco.2024.2727
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