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Pre-hepatectomy dynamic circulating tumor DNA to predict pathologic response to preoperative chemotherapy and post-hepatectomy recurrence in patients with colorectal liver metastases

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Abstract

Objective

To evaluate the predictive value of pre-hepatectomy dynamic circulating tumor DNA (ctDNA) on pathologic response to preoperative chemotherapy and recurrence after liver resection for colorectal liver metastases (CRLM).

Background

Pathologic response is a predictor of clinical outcomes for patients undergoing hepatectomy for CRLM. Postoperative ctDNA has been proven to be sensitive for recurrence detection. However, few studies investigate the impact of pre-hepatectomy ctDNA on pathologic response and recurrence.

Methods

Patients with potential resectable CRLM underwent preoperative chemotherapy and hepatectomy between 2018 and 2021 was considered for inclusion. Plasma ctDNA was collected before and after preoperative chemotherapy. Pathologic response was analyzed for all patients after liver resection. Recurrence free survival was compared between patients with different ctDNA status and different pathologic response. The relation between ctDNA and pathologic response was also analyzed.

Results

A total of 114 patients were included. ctDNA was detectable in 108 of 114 patients (94.7%) before chemotherapy, in 56 of 114 patients (49.1%) after chemotherapy. Patients with ctDNA positive at baseline and negative after chemotherapy had significantly longer RFS (median RFS 17 vs 7 months, p = 0.001) and HRFS (median HRFS unreached vs 8 months, p < 0.001) than those with ctDNA persistently positive after chemotherapy. Two patients (1.6%) had a pathologic complete response and 56 patients (45.2%) had a pathologic major response. Post-chemotherapy ctDNA− was associated with improved major pathologic response (53.4% vs 32.1%, p = 0.011). In the multivariable analysis, ctDNA− after chemotherapy (HR 0.51, 95% CI 0.28–0.93), major pathologic response (HR 0.34, 95% CI 0.19–0.62) and surgery combined with radiofrequency ablation (HR 2.62, 95% CI 1.38–5.00) were independently associated with RFS (all p < 0.05).

Conclusions

Pre-hepatectomy dynamic monitoring of ctDNA could predict pathologic response to preoperative chemotherapy and post-hepatectomy recurrence in CRLM patients. Negative ctDNA after preoperative chemotherapy was associated with better tumor regression grade and recurrence-free survival, which might be used to guide pre-hepatectomy chemotherapy and predict prognosis.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Funding

This research was supported by the Clinical Research Fund For Distinguished Young Scholars of Beijing Cancer Hospital (No. LGH2022005) and grants from the National Nature Science Foundation of China (No. 31971192).

Author information

Author notes

  1. Ming Liu and Quan Bao have contributed equally.

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Biliary-Pancreatic Surgery I, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing, People’s Republic of China

    Ming Liu, Quan Bao, Yanyan Wang, Xiaoluan Yan, Hongwei Wang, Kemin Jin, Wei Liu, Kun Wang & Baocai Xing

  2. GloriousMed Clinical Laboratory (Shanghai) Co., Ltd., Shanghai, People’s Republic of China

    Tingting Zhao, Longfei Huang & Danhua Zhang

Authors
  1. Ming Liu
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Corresponding authors

Correspondence to Kun Wang or Baocai Xing.

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Conflict of interest

There are no conflicts of interest for all the authors who participate in this study, including Ming Liu, Quan Bao, Tingting Zhao, Longfei Huang, Danhua Zhang, Yanyan Wang, Xiaoluan Yan, Hongwei Wang, Kemin Jin, Wei Liu, Kun Wang and Baocai Xing.

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Fig. S1 Study flow. NED: no evidence of disease. (TIFF 35159 KB)

12072_2023_10628_MOESM2_ESM.tiff

Fig. S2 Plots of HRFS stratified by ctDNA fraction. A) HRFS stratified by ctDNA dynamics peri-chemotherapy, ctDNA +/-, ctDNA -/- and ctDNA +/+. B) HRFS stratified by baseline ctDNA status. C) HRFS stratified by the post-chemotherapy ctDNA status. (TIFF 33973 KB)

Supplementary file3 (DOCX 20 KB)

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Liu, M., Bao, Q., Zhao, T. et al. Pre-hepatectomy dynamic circulating tumor DNA to predict pathologic response to preoperative chemotherapy and post-hepatectomy recurrence in patients with colorectal liver metastases. Hepatol Int (2024). https://doi.org/10.1007/s12072-023-10628-4

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