Tumor-Boundary Response Index (TBRI)- A promising indicator for predicting outcomes in colorectal liver metastases receiving neoadjuvant therapy: Insights from a single-center retrospective study

Yin-Chen Gu; Mei Yang; Yan Geng; Bo Zhang; Bao-Rui Tao; Sen-Feng Ying; Rong-Quan Sun; Yi-Tong Li; Zhen-Mei Chen; Chen-He Yi; Jin Lin; Rui Zhang; Jie Fan; Xiang-Yu Wang; Jin-Hong Chen

doi:10.1016/j.ejso.2025.110291

Tumor-Boundary Response Index (TBRI)- A promising indicator for predicting outcomes in colorectal liver metastases receiving neoadjuvant therapy: Insights from a single-center retrospective study

Eur J Surg Oncol. 2025 Jun 24;51(10):110291. doi: 10.1016/j.ejso.2025.110291. Online ahead of print.

Authors

Yin-Chen Gu¹, Mei Yang², Yan Geng¹, Bo Zhang¹, Bao-Rui Tao¹, Sen-Feng Ying¹, Rong-Quan Sun¹, Yi-Tong Li¹, Zhen-Mei Chen¹, Chen-He Yi¹, Jin Lin¹, Rui Zhang¹, Jie Fan³, Xiang-Yu Wang⁴, Jin-Hong Chen⁵

Affiliations

¹ Hepatobiliary Surgery, Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China.
² Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China.
³ Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: fanjie@fudan.edu.cn.
⁴ Hepatobiliary Surgery, Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China. Electronic address: wangxymed@163.com.
⁵ Hepatobiliary Surgery, Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China. Electronic address: jinhongch@hotmail.com.

PMID: 40652823
DOI: 10.1016/j.ejso.2025.110291

Abstract

Background: Tumor regression grade (TRG) and histopathological growth pattern (HGP) reflect the response of colorectal liver metastases (CRLM) to neoadjuvant therapy (NAT) from the perspectives of the tumor and its microenvironment, respectively. Based on these two indicators, this study aimed to develop a prognostic index for CRLM undergoing surgery after NAT.

Materials and methods: 237 patients who underwent curative-intent resection following NAT from 2012 to 2022 were selected. Correlations between HGP and TRG were assessed. Cox regression analyses were employed to determine the optimal cut-off point for constructing the Tumor-Boundary Response Index (TBRI). Kaplan-Meier analyses of overall survival (OS), disease-free survival (DFS) and hepatic relapse-free survival (hRFS) were used to evaluate the prognostic value. The predictive ability of TBRI, Fong's clinical risk score (CRS) and Genetic And Morphological Evaluation (GAME) score was compared by time-dependent receiver operating characteristic (ROC) analysis. Calibration plot was utilized to assess the goodness of fit.

Results: Desmoplastic HGP (dHGP) exhibited an inverse correlation with TRG in lesions. TBRI stratified patients into four tiers based on whether HGP is predominant desmoplastic (>50 %) and whether TRG is ≤ 3, showing significant prognostic value in OS, DFS and hRFS (median OS for TBRI 1-4: 78.6, 42.6, 27.8 and 22.5, p < 0.001; median DFS for TBRI 1-4: 22.4, 12.4, 10.9 and 6.5 months, p < 0.001; median hRFS for TBRI 1-4: 29.2, 12.9, 10.9, 6.8, p < 0.001). Additionally, TBRI surpassed CRS and GAME score with superior discriminatory power and displayed exceptional consistency.

Conclusions: TBRI demonstrated a promising ability to predict the postoperative survival of CRLM patients receiving NAT.

Keywords: Colorectal liver metastases; Histopathological growth pattern; Neoadjuvant therapy; Tumor regression grade; Tumor-Boundary response index.