Open Access Peer-reviewed Commentary

Opportunities and challenges of multidisciplinary conversion therapy in advanced hepatocellular carcinoma

Article Sidebar

The roadmap for conversion therapy
Download PDF
Submitted   Jul 31, 2024
Published   Sep 11, 2024
Issue    Vol 6 (2024)
DOI   10.25082/CCR.2024.01.003

Views

253

Downloads

58

Citations

PlumX Metrics

Main Article Content

Ju-Hang Chu
Department of General Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
Lu-Yao Huang
Department of General Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
Ya-Ru Wang
Department of General Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
Jun Li
Department of General Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
Ying-Yu Cui corresponding author
1. Department of Cell Biology, Tongji University School of Medicine, Shanghai 200331, China; 2. Institute of Medical Genetics, Tongji University School of Medicine, Shanghai 200331, China; 3. State Key Laboratory of Cardiology, Tongji University School of Medicine, Shanghai 200331, China
Ming-Ping Qian
1. Department of General Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; 2. Department of General Surgery, Shanghai Tenth People's Hospital Chongming Branch, Shanghai 202150, China

Abstract

Surgical resection is still the most important radical treatment for primary hepatocellular carcinoma (HCC), but at present, the resection rate of newly diagnosed patients with HCC is only 30%. The recurrence rate of newly diagnosed patients suitable for surgical resection within 5 years after surgery is as high as 40%~70%. Low initial resection rate and high postoperative recurrence rate are important reasons restricting the overall treatment effects of HCC in China. Under this background, effectively improving the resection rate of HCC and reducing the postoperative recurrence rate have become the key topics to improve the treatment effects of HCC. Some initially unresectable HCC patients may have access to surgery through conversion therapy. Conversion therapy, which mainly involves the combination of local, systemic, and multiple treatment strategies, offers hope for patients with advanced HCC. But there are still some patients who do not benefit from conversion therapy. So, how to improve the conversion success rate is still one of the challenges that clinicians need to solve.

Keywords
hepatocellular carcinoma, conversion therapy, multidisciplinary therapy

Article Details

Supporting Agencies
2023 Key R&D Projects of Tongji University (No. 150029607160-24323); Chongming District, Shanghai `Scientific and Technological Innovation Action Plan for Sustainable Development' (CKY2023-37).
How to Cite
Chu, J.-H., Huang, L.-Y., Wang, Y.-R., Li, J., Cui, Y.-Y., & Qian, M.-P. (2024). Opportunities and challenges of multidisciplinary conversion therapy in advanced hepatocellular carcinoma. Current Cancer Reports, 6(1), 225-229. https://doi.org/10.25082/CCR.2024.01.003
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

References

  1. Zuo M, Zheng G, Cao Y, et al. Hepatic arterial chemotherapy infusion combined with tyrosine kinase inhibitors and PD-1 inhibitors for advanced hepatocellular carcinoma with high-risk: A propensity score matching study. International Journal of Surgery. Published online July 12, 2024. https://doi.org/10.1097/js9.0000000000001940
  2. Lin YD, Wu GS, Rao MY, et al. Effect of cytokines on advanced hepatocellular carcinoma prognosis receiving radiotherapy and tislelizumab plus anlotinib: a single-center phase II clinical trial. Scientific Reports. 2024, 14(1). https://doi.org/10.1038/s41598-024-62523-z
  3. Tada T, Kumada T, Hiraoka A, et al. Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real‐world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial. Alimentary Pharmacology & Therapeutics. 2024, 60(2): 233-245. https://doi.org/10.1111/apt.18037
  4. Melero I, Yau T, Kang YK, et al. Nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma previously treated with sorafenib: 5-year results from CheckMate 040. Annals of Oncology. 2024, 35(6): 537-548. https://doi.org/10.1016/j.annonc.2024.03.005
  5. Chiang CL, Chiu KWH, Chan KSK, et al. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial. The Lancet Gastroenterology & Hepatology. 2023, 8(2): 169-178. https://doi.org/10.1016/s2468-1253(22)00339-9
  6. Liu D, Mu H, Liu C, et al. Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: a prospective, single-arm phase II trial. Neoplasma. 2024, 70(06): 811-818. https://doi.org/10.4149/neo_2023_230806n413
  7. Zhang W, Tong S, Hu B, et al. Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial. Journal for ImmunoTherapy of Cancer. 2023, 11(9): e007366. https://doi.org/10.1136/jitc-2023-007366
  8. Li J, Kong M, Yu G, et al. Safety and efficacy of transarterial chemoembolization combined with tyrosine kinase inhibitors and camrelizumab in the treatment of patients with advanced unresectable hepatocellular carcinoma. Frontiers in Immunology. 2023, 14. https://doi.org/10.3389/fimmu.2023.1188308
  9. Chen B, Huang B. Predictive factors for transition to conversion therapy in HCC using atezolizumab plus bevacizumab. Liver International. 2024, 44(7): 1735-1735. https://doi.org/10.1111/liv.15944
  10. Zhang Y, Ma Y, Wang E, et al. Conversion therapy for advanced biphenotypic hepatocellular carcinoma: A case report. Asian Journal of Surgery. Published online July 2024. https://doi.org/10.1016/j.asjsur.2024.07.016
  11. Wu J long, Peng P, Hu Z min, et al. A case of conversion therapy for hepatocellular carcinoma with bile-duct tumor thrombus. Asian Journal of Surgery. 2024, 47(8): 3688-3689. https://doi.org/10.1016/j.asjsur.2024.04.039
  12. Yau T, Zagonel V, Santoro A, et al. Nivolumab Plus Cabozantinib With or Without Ipilimumab for Advanced Hepatocellular Carcinoma: Results From Cohort 6 of the CheckMate 040 Trial. Journal of Clinical Oncology. Published online December 13, 2022. https://doi.org/10.1200/jco.22.00972
  13. Chen S, Shi F, Wu Z, et al. Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Tislelizumab with or Without Transhepatic Arterial Embolization for Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombus and High Tumor Burden: A Multicenter Retrospective Study. Journal of Hepatocellular Carcinoma. 2023, 10: 1209-1222. https://doi.org/10.2147/jhc.s417550
  14. Liu R, Qian MP, Cui YY. Protein kinases: The key contributors in pathogenesis and treatment of nonalcoholic fatty liver disease-derived hepatocellular carcinoma. Metabolism. 2023, 147: 155665. https://doi.org/10.1016/j.metabol.2023.155665
  15. Zhu XD, Huang C, Shen YH, et al. Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations. Liver Cancer. 2021, 10(4): 320-329. https://doi.org/10.1159/000514313
  16. LIN ZP, HU XL, CHEN D, et al. Clinical efficacy of targeted therapy, immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX), and lipiodol embolization in the treatment of unresectable hepatocarcinoma. Journal of Physiology & Pharmacology, 2022, 73(6).
  17. Zhang J, Zhang X, Mu H, et al. Surgical Conversion for Initially Unresectable Locally Advanced Hepatocellular Carcinoma Using a Triple Combination of Angiogenesis Inhibitors, Anti-PD-1 Antibodies, and Hepatic Arterial Infusion Chemotherapy: A Retrospective Study. Frontiers in Oncology. 2021, 11. https://doi.org/10.3389/fonc.2021.729764
  18. Finn RS, Ikeda M, Zhu AX, et al. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. Journal of Clinical Oncology. 2020, 38(26): 2960-2970. https://doi.org/10.1200/jco.20.00808
  19. Song WJ, Xu J, Nie Y, et al. Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus: A case report and review of literature. World Journal of Clinical Cases. 2024, 12(16): 2847-2855. https://doi.org/10.12998/wjcc.v12.i16.2847
  20. Zhao W, Liu C, Wu Y, et al. Transarterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC) combined with PD-1 inhibitors plus lenvatinib as a preoperative conversion therapy for nonmetastatic advanced hepatocellular carcinoma: a single center experience. Translational Cancer Research. 2024, 13(5): 2315-2331. https://doi.org/10.21037/tcr-24-93
  21. Shimose S, Saeki I, Tomonari T, et al. Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice. Oncology Letters. 2024, 28(2). https://doi.org/10.3892/ol.2024.14530
  22. Sangro B, Galle PR, Kelley RK, et al. Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma. Journal of Clinical Oncology. 2024, 42(23): 2790-2799. https://doi.org/10.1200/jco.23.01462
  23. Sangro B, Chan SL, Kelley RK, et al. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Annals of Oncology. 2024, 35(5): 448-457. https://doi.org/10.1016/j.annonc.2024.02.005
  24. Wang M, Xu X, Wang K, et al. Conversion therapy for advanced hepatocellular carcinoma in the era of precision medicine: Current status, challenges and opportunities. Cancer Science. 2024, 115(7): 2159-2169. https://doi.org/10.1111/cas.16194
  25. Li X, Chen J, Wang X, et al. Outcomes and prognostic factors in initially unresectable hepatocellular carcinoma treated using conversion therapy with lenvatinib and TACE plus PD-1 inhibitors. Frontiers in Oncology. 2023, 13. https://doi.org/10.3389/fonc.2023.1110689
  26. Guo B, Zhou Y, Liu Z, et al. TACE plus PD-1 successfully achieves conversion therapy for unresectable HCC with multiple macrovascular invasion: Case report. Clinics and Research in Hepatology and Gastroenterology. 2023, 47(7): 102169. https://doi.org/10.1016/j.clinre.2023.102169
  27. Pang B, Zuo B, Huang L, et al. Real-world efficacy and safety of TACE-HAIC combined with TKIs and PD-1 inhibitors in initially unresectable hepatocellular carcinoma. International Immunopharmacology. 2024, 137: 112492. https://doi.org/10.1016/j.intimp.2024.112492
  28. Tang Z, Bai T, Wei T, et al. TACE combined Lenvatinib plus Camrelizumab versus TACE alone in efficacy and safety for unresectable hepatocellular carcinoma: a propensity score-matching study. BMC Cancer. 2024, 24(1). https://doi.org/10.1186/s12885-024-12484-3
  29. He M, Li Q, Zou R, et al. Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion. JAMA Oncology. 2019, 5(7): 953. https://doi.org/10.1001/jamaoncol.2019.0250
  30. Chang X, Li X, Sun P, et al. HAIC Combined with lenvatinib plus PD-1 versus lenvatinib Plus PD-1 in patients with high-risk advanced HCC: a real-world study. BMC Cancer. 2024, 24(1). https://doi.org/10.1186/s12885-024-12233-6
  31. Liu J, Li Z, Zhang W, et al. Comprehensive Treatment of Trans-Arterial Chemoembolization Plus Lenvatinib Followed by Camrelizumab for Advanced Hepatocellular Carcinoma Patients. Frontiers in Pharmacology. 2021, 12. https://doi.org/10.3389/fphar.2021.709060
  32. Jiang X, Aljbri A, Liu J, et al. Hepatic arterial infusion chemotherapy with implantable arterial access port for advanced-stage hepatocellular carcinoma: a case report. Frontiers in Oncology. 2024, 14. https://doi.org/10.3389/fonc.2024.1401882
  33. Liang C, He Z, Tao Q, et al. From Conversion to Resection for Unresectable Hepatocellular Carcinoma: A Review of the Latest Strategies. Journal of Clinical Medicine. 2023, 12(24): 7665. https://doi.org/10.3390/jcm12247665
  34. Sato S, Aoki T, Matsumoto T, et al. Pathological complete response of hepatocellular carcinoma confirmed by conversion hepatectomy following atezolizumab plus bevacizumab therapy: a case report and literature review. Clinical Journal of Gastroenterology. 2023, 17(2): 292-299. https://doi.org/10.1007/s12328-023-01895-7
  35. Takamoto T, Maruki Y, Kondo S. Recent updates in the use of pharmacological therapies for downstaging in patients with hepatocellular carcinoma. Expert Opinion on Pharmacotherapy. 2023, 24(14): 1567-1575. https://doi.org/10.1080/14656566.2023.2229728
  36. Chu JH, Huang LY, Wang YR, et al. Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy: A case report and review of literature. World Journal of Gastrointestinal Oncology. 2024, 16(4): 1647-1659. https://doi.org/10.4251/wjgo.v16.i4.1647