Development and validation of a predictive model for objective response rate in unresectable hepatocellular carcinoma treated with TACE combined with targeted therapy and immunotherapy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Hongyuan ¹ , XIE Qingyun ² , ZHAO Xin ³ , JIANG Kangyi ⁴ , ZHENG Peng ¹ , ZHOU Heng ¹ , MAO Tianyang ⁴ , LIU Zhuoran ⁴ ,  GAO Fengwei ²

1. College of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;
2. Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
3. Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
4. Department of Hepatobiliary & Pancreatic Surgery, The People’s Hospital of Leshan, Leshan, Sichuan 614000, P. R. China;

Corresponding?author：

GAO Fengwei, Email: gaofengwei@scu.edu.cn

Keywords：

hepatocellular carcinoma; transarterial chemoembolization; targeted therapy; immunotherapy; tumor response

DOI：

10.7507/1007-9424.202601164

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To develop a nomogram prediction model for predicting the objective response rate (ORR) in patients with unresectable hepatocellular carcinoma (uHCC) receiving transarterial chemoembolization (TACE) combined with targeted therapy and immunotherapy. Methods Clinicopathological data of uHCC patients treated with TACE combined with targeted therapy and immunotherapy at Leshan People’s Hospital from January 2018 to November 2023 were collected. Patients were randomly divided into a training set and a validation set at a 7∶3 ratio. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for ORR. Variables with P<0.05 in the multivariate analysis, together with clinically important factors [such as Eastern Cooperative Oncology Group performance status (ECOG PS) score and portal vein tumor thrombus (PVTT)], were incorporated into the nomogram model. Model performance and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curves, and decision curve analysis. Results A total of 105 patients with uHCC were enrolled, including 73 in the training set and 32 in the validation set. Multivariate logistic regression analysis identified alpha-fetoprotein (AFP), Barcelona Clinic Liver Cancer (BCLC) stage, and prothrombin time (PT) as independent predictors of ORR (P<0.05). The nomogram incorporating these factors along with ECOG PS score and PVTT achieved AUCs (95%CI) of 0.81 (0.71, 0.91) in the training set and 0.80 (0.64, 0.96) in the validation set. Bootstrap internal validation (1 000 resamples) yielded a mean C-index (95%CI) of 0.76 (0.63, 0.89). The Hosmer-Lemeshow test indicated good model fit (training set: χ²=5.64, P=0.58; validation set: χ²=3.89, P=0.69), and calibration curves showed close alignment with the ideal diagonal in both sets. Decision curve analysis demonstrated positive net clinical benefit within threshold probability ranges of 0.02–0.78 (training set) and 0.10–0.80 (validation set). Conclusion The nomogram prediction model based on AFP, BCLC stage, PT, ECOG PS score, and PVTT effectively predicts ORR in uHCC patients receiving TACE combined with targeted therapy and immunotherapy, providing a reference for individualized treatment decisions.

Citation： WANG Hongyuan, XIE Qingyun, ZHAO Xin, JIANG Kangyi, ZHENG Peng, ZHOU Heng, MAO Tianyang, LIU Zhuoran, GAO Fengwei. Development and validation of a predictive model for objective response rate in unresectable hepatocellular carcinoma treated with TACE combined with targeted therapy and immunotherapy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(3): 317-323. doi: 10.7507/1007-9424.202601164 Copy

1.	董赟芳, 劉鋒, 陳鵬. 肝癌自發破裂機制及診治的研究進展. 中國普外基礎與臨床雜志, 2025, 32(7): 903-910.
2.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
3.	Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6. doi: 10.1038/s41572-020-00240-3.
4.	Cai X. Laparoscopic liver resection: the current status and the future. Hepatobiliary Surg Nutr, 2018, 7(2): 98-104.
5.	Kanwal F, Befeler A, Chari RS, et al. Potentially curative treatment in patients with hepatocellular cancer—results from the liver cancer research network. Aliment Pharmacol Ther, 2012, 36(3): 257-265.
6.	Villanueva A. Hepatocellular Carcinoma. N Engl J Med, 2019, 380(15): 1450-1462.
7.	Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol, 2022, 76(3): 681-693.
8.	Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology, 2018, 67(1): 358-380.
9.	Wang L, Lin L, Zhou W. Efficacy and safety of transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor in the treatment of advanced hepatocellular carcinoma: a meta-analysis. Pharmacol Ther, 2024, 257: 108634. doi: 10.1016/j.pharmthera.2024.108634.
10.	Cai M, Huang W, Huang J, et al. Transarterial chemoembolization combined with lenvatinib plus PD-1 inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study. Front Immunol, 2022, 13: 848387. doi: 10.3389/fimmu.2022.848387.
11.	Wu XK, Yang LF, Chen YF, et al. Transcatheter arterial chemoembolisation combined with lenvatinib plus camrelizumab as conversion therapy for unresectable hepatocellular carcinoma: a single-arm, multicentre, prospective study. EClinicalMedicine, 2023, 67: 102367. doi: 10.1016/j.eclinm.2023.102367.
12.	Kudo M, Ren Z, Guo Y, et al. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. Lancet, 2025, 405(10474): 203-215.
13.	Loosen SH, Schulze-Hagen M, Leyh C, et al. IL-6 and IL-8 serum levels predict tumor response and overall survival after TACE for primary and secondary hepatic malignancies. Int J Mol Sci, 2018, 19(6): 1766. doi: 10.3390/ijms19061766.
14.	Miura R, Ono A, Nakahara H, et al. Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma. J Gastroenterol, 2025, 60(3): 328-339.
15.	Yang F, Xu GL, Huang JT, et al. Transarterial chemoembolization combined with immune checkpoint inhibitors and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: efficacy and systemic immune response. Front Immunol, 2022, 13: 847601. doi: 10.3389/fimmu.2022.847601.
16.	Zeng Y, Gu J, He W, et al. Dynamic changes in serum alpha-fetoprotein predict prognosis in hepatocellular carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Therap Adv Gastroenterol, 2025, 18: 17562848251387501. doi: 10.1177/17562848251387501.
17.	Hoshida Y, Nijman SM, Kobayashi M, et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res, 2009, 69(18): 7385-7392.
18.	Wang H, Xiang Y, Li X, et al. High lymphocyte-to-monocyte ratio is associated with low α-fetoprotein expression in patients with hepatitis B virus-associated hepatocellular carcinoma. Mol Med Rep, 2020, 22(4): 2673-2684.
19.	張搏倫. 第一部分, 聯合基因組及轉錄組分析揭示粗梁實體型肝細胞癌分子特征; 第二部分, 基于LFNII評分預測甲胎蛋白陰性肝癌術后復發的列線圖模型的構建與驗證. 北京: 北京協和醫學院, 2024.
20.	宋佳悅, 袁權, 車雨東, 等. 基于PIVKA-Ⅱ、AFP檢測和機器學習算法的肝癌診斷預測模型性能分析. 中西醫結合肝病雜志, 2024, 34(9): 775-780.
21.	Yao F, Miao J, Quan B, et al. Predicting resistance and survival of HCC patients post-HAIC: based on shapley additive explanations and machine learning. J Hepatocell Carcinoma, 2025, 12: 1111-1128.
22.	Ninomiya M, Tsuruoka M, Inoue J, et al. A new model to predict survival time in patients with hepatocellular carcinoma with BCLC advanced stage. Cancer Med, 2025, 14(20): e71299. doi: 10.1002/cam4.71299.
23.	Fukumura D, Kloepper J, Amoozgar Z, et al. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol, 2018, 15(5): 325-340.
24.	于瑞娜, 董剛, 孫璐璐, 等. 術前超聲造影參數達峰時間、峰值強度與肝硬化背景下肝細胞癌預后的關聯性. 鄭州大學學報(醫學版), 2025, 60(5): 686-689.
25.	Liu X, Zeng B, Liu J, et al. A nomogram for predicting overall survival in advanced hepatocellular carcinoma patients receiving radiotherapy combined with targeted therapy: a multicenter retrospective study. Transl Cancer Res, 2025, 14(9): 5245-5254.
26.	Deng LW, Xie QY, Peng B, et al. Predicting tumor response to TACE plus lenvatinib and PD-1 inhibitors for unresectable HCC: a multicenter observational study. Eur J Radiol, 2025, 192: 112401. doi: 10.1016/j.ejrad.2025.112401.
27.	Liao SN, Li T, Liu ZH, et al. Association of TIMP-2 expression with postoperative prognosis in hepatocellular carcinoma patients and development of a predictive model. J Inflamm Res, 2025, 18: 11703-11736.
28.	王秀珍, 譚瑩, 崔新江, 等. NLR、AFP聯合ALBI評分對TACE聯合微波消融治療巨塊型肝癌患者預后的預測價值. 轉化醫學雜志, 2025, 14(1): 69-73.
29.	Li S, Wu J, Wu J, et al. Prediction of early treatment response to the combination therapy of TACE plus lenvatinib and anti-PD-1 antibody immunotherapy for unresectable hepatocellular carcinoma: multicenter retrospective study. Front Immunol, 2023, 14: 1109771. doi: 10.3389/fimmu.2023.1109771.

1. 董赟芳, 劉鋒, 陳鵬. 肝癌自發破裂機制及診治的研究進展. 中國普外基礎與臨床雜志, 2025, 32(7): 903-910.
2. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
3. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6. doi: 10.1038/s41572-020-00240-3.
4. Cai X. Laparoscopic liver resection: the current status and the future. Hepatobiliary Surg Nutr, 2018, 7(2): 98-104.
5. Kanwal F, Befeler A, Chari RS, et al. Potentially curative treatment in patients with hepatocellular cancer—results from the liver cancer research network. Aliment Pharmacol Ther, 2012, 36(3): 257-265.
6. Villanueva A. Hepatocellular Carcinoma. N Engl J Med, 2019, 380(15): 1450-1462.
7. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol, 2022, 76(3): 681-693.
8. Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology, 2018, 67(1): 358-380.
9. Wang L, Lin L, Zhou W. Efficacy and safety of transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor in the treatment of advanced hepatocellular carcinoma: a meta-analysis. Pharmacol Ther, 2024, 257: 108634. doi: 10.1016/j.pharmthera.2024.108634.
10. Cai M, Huang W, Huang J, et al. Transarterial chemoembolization combined with lenvatinib plus PD-1 inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study. Front Immunol, 2022, 13: 848387. doi: 10.3389/fimmu.2022.848387.
11. Wu XK, Yang LF, Chen YF, et al. Transcatheter arterial chemoembolisation combined with lenvatinib plus camrelizumab as conversion therapy for unresectable hepatocellular carcinoma: a single-arm, multicentre, prospective study. EClinicalMedicine, 2023, 67: 102367. doi: 10.1016/j.eclinm.2023.102367.
12. Kudo M, Ren Z, Guo Y, et al. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. Lancet, 2025, 405(10474): 203-215.
13. Loosen SH, Schulze-Hagen M, Leyh C, et al. IL-6 and IL-8 serum levels predict tumor response and overall survival after TACE for primary and secondary hepatic malignancies. Int J Mol Sci, 2018, 19(6): 1766. doi: 10.3390/ijms19061766.
14. Miura R, Ono A, Nakahara H, et al. Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma. J Gastroenterol, 2025, 60(3): 328-339.
15. Yang F, Xu GL, Huang JT, et al. Transarterial chemoembolization combined with immune checkpoint inhibitors and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: efficacy and systemic immune response. Front Immunol, 2022, 13: 847601. doi: 10.3389/fimmu.2022.847601.
16. Zeng Y, Gu J, He W, et al. Dynamic changes in serum alpha-fetoprotein predict prognosis in hepatocellular carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Therap Adv Gastroenterol, 2025, 18: 17562848251387501. doi: 10.1177/17562848251387501.
17. Hoshida Y, Nijman SM, Kobayashi M, et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res, 2009, 69(18): 7385-7392.
18. Wang H, Xiang Y, Li X, et al. High lymphocyte-to-monocyte ratio is associated with low α-fetoprotein expression in patients with hepatitis B virus-associated hepatocellular carcinoma. Mol Med Rep, 2020, 22(4): 2673-2684.
19. 張搏倫. 第一部分, 聯合基因組及轉錄組分析揭示粗梁實體型肝細胞癌分子特征; 第二部分, 基于LFNII評分預測甲胎蛋白陰性肝癌術后復發的列線圖模型的構建與驗證. 北京: 北京協和醫學院, 2024.
20. 宋佳悅, 袁權, 車雨東, 等. 基于PIVKA-Ⅱ、AFP檢測和機器學習算法的肝癌診斷預測模型性能分析. 中西醫結合肝病雜志, 2024, 34(9): 775-780.
21. Yao F, Miao J, Quan B, et al. Predicting resistance and survival of HCC patients post-HAIC: based on shapley additive explanations and machine learning. J Hepatocell Carcinoma, 2025, 12: 1111-1128.
22. Ninomiya M, Tsuruoka M, Inoue J, et al. A new model to predict survival time in patients with hepatocellular carcinoma with BCLC advanced stage. Cancer Med, 2025, 14(20): e71299. doi: 10.1002/cam4.71299.
23. Fukumura D, Kloepper J, Amoozgar Z, et al. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol, 2018, 15(5): 325-340.
24. 于瑞娜, 董剛, 孫璐璐, 等. 術前超聲造影參數達峰時間、峰值強度與肝硬化背景下肝細胞癌預后的關聯性. 鄭州大學學報(醫學版), 2025, 60(5): 686-689.
25. Liu X, Zeng B, Liu J, et al. A nomogram for predicting overall survival in advanced hepatocellular carcinoma patients receiving radiotherapy combined with targeted therapy: a multicenter retrospective study. Transl Cancer Res, 2025, 14(9): 5245-5254.
26. Deng LW, Xie QY, Peng B, et al. Predicting tumor response to TACE plus lenvatinib and PD-1 inhibitors for unresectable HCC: a multicenter observational study. Eur J Radiol, 2025, 192: 112401. doi: 10.1016/j.ejrad.2025.112401.
27. Liao SN, Li T, Liu ZH, et al. Association of TIMP-2 expression with postoperative prognosis in hepatocellular carcinoma patients and development of a predictive model. J Inflamm Res, 2025, 18: 11703-11736.
28. 王秀珍, 譚瑩, 崔新江, 等. NLR、AFP聯合ALBI評分對TACE聯合微波消融治療巨塊型肝癌患者預后的預測價值. 轉化醫學雜志, 2025, 14(1): 69-73.
29. Li S, Wu J, Wu J, et al. Prediction of early treatment response to the combination therapy of TACE plus lenvatinib and anti-PD-1 antibody immunotherapy for unresectable hepatocellular carcinoma: multicenter retrospective study. Front Immunol, 2023, 14: 1109771. doi: 10.3389/fimmu.2023.1109771.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Development and validation of a predictive model for objective response rate in unresectable hepatocellular carcinoma treated with TACE combined with targeted therapy and immunotherapy

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content