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The Clinical Value of Postoperative Transarterial Chemoembolization for Resectable Patients with Intermediate Hepatocellular Carcinoma After Radical Hepatectomy: a Propensity Score-Matching Study

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background and Aims

Surgical resection for patients with intermediate hepatocellular carcinoma (HCC) is preferred in China, but the prognosis remains far from satisfactory. Postoperative transarterial chemoembolization (p-TACE) has been conducted prevalently to prevent recurrence, but its efficacy remains controversial. Hence, we collected the data from primary liver cancer big data (PLCBD) to investigate the clinical value of p-TACE for patients with intermediate HCC and identify the potential beneficiaries.

Methods

Patients who were diagnosed with intermediate HCC between December 2012 and December 2015 were identified through the PLCBD. Disease-free survival (DFS) of patients who received p-TACE or not following radical resection was evaluated using Kaplan-Meier survival curves before and after 1:1 propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors associated with recurrence.

Results

A total of 325 intermediate HCC patients receiving radical resection were eligible in this study, including 123 patients in the p-TACE group and 202 in the non-TACE group. Median DFS in the p-TACE group was significantly longer than in the non-TACE group (23.3 months vs. 18.0 months, P = 0.016) in the whole cohort with no severe complicates, which was confirmed in a well-matched cohort (17.4 months vs. 23.3 months, P = 0.012). In addition, p-TACE was identified as an independent risk factors of DFS by multivariate Cox regression analysis before and after PSM (both P < 0.05). After adjusting for other prognostic variables, patients were found to significantly benefit from p-TACE in DFS if they were male, or had hepatitis, diabetes, cirrhosis, AFP ≤ 400 ng/ml, anatomic hepatectomy, no severe surgical complication, no intraoperative transfusion, tumor number = 2, differentiation grading III, capsule, or had no transfusion (all P < 0.05).

Conclusion

With the current data, we concluded that p-TACE was safe and efficient for the patients with intermediate HCC following radical resection, and male patients with hepatitis, diabetes, cirrhosis, AFP ≤ 400 ng/ml, anatomic hepatectomy, no severe surgical complication, no intraoperative transfusion, tumor number = 2, differentiation grading III, and capsule would benefit more from p-TACE.

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References

  1. Hilmi M, Neuzillet C, Calderaro J, et al. Angiogenesis and immune checkpoint inhibitors as therapies for hepatocellular carcinoma: current knowledge and future research directions[J]. J Immunother Cancer 2019, 7(1): 333.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ma J, Zheng B, Goswami S, et al. PD1(Hi) CD8(+) T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma[J]. J Immunother Cancer 2019, 7(1): 331.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kostadinova L, Shive C L, Anthony D D. Elevated autotaxin and LPA levels during chronic viral hepatitis and hepatocellular carcinoma associate with systemic immune activation[J]. Cancers (Basel) 2019, 11(12): 1867.

    Article  CAS  Google Scholar 

  4. Zhang P, Luo H, Zhu W, et al. Real-time navigation for laparoscopic hepatectomy using image fusion of preoperative 3D surgical plan and intraoperative indocyanine green fluorescence imaging[J]. Surg Endosc 2019.

  5. Siegel R L, Miller K D, Jemal A. Cancer statistics, 2019[J]. CA Cancer J Clin 2019, 69(1): 7-34.

    Article  PubMed  Google Scholar 

  6. Ruiz D G M, Lujambio A. Hepatocellular carcinoma: killing one bird with two stones[J]. Gut. 2019, 68(9): 1543-1544.

    Article  CAS  Google Scholar 

  7. Forner A, Reig M, Bruix J. Hepatocellular carcinoma[J]. Lancet. 2018, 391(10127): 1301-1314.

    Article  PubMed  Google Scholar 

  8. Benson A B, D'Angelica M I, Abbott D E, et al. Guidelines insights: hepatobiliary cancers, Version 2.2019[J]. J Natl Compr Cancer Netw 2019, 17(4): 302-310.

    Article  CAS  Google Scholar 

  9. Chevret S, Trinchet J C, Mathieu D, et al. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire[J]. J Hepatol 1999, 31(1): 133-141.

    Article  CAS  PubMed  Google Scholar 

  10. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators[J]. Hepatology. 1998, 28(3): 751-755.

  11. Leung T W, Tang A M, Zee B, et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients[J]. Cancer. 2002, 94(6): 1760-1769.

    Article  PubMed  Google Scholar 

  12. Yau T, Tang V Y, Yao T J, et al. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma[J]. Gastroenterology. 2014, 146(7): 1691-1700.

    Article  PubMed  Google Scholar 

  13. Kudo M, Chung H, Haji S, et al. Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score[J]. Hepatology. 2004, 40(6): 1396-1405.

    Article  PubMed  Google Scholar 

  14. Hiraoka A, Kumada T, Michitaka K, et al. Newly proposed ALBI grade and ALBI-T score as tools for assessment of hepatic function and prognosis in hepatocellular carcinoma patients[J]. Liver Cancer 2019, 8(5): 312-325.

    Article  CAS  PubMed  Google Scholar 

  15. Tsilimigras D I, Mehta R, Moris D, et al. Utilizing machine learning for pre- and postoperative assessment of patients undergoing resection for BCLC-0, A and B hepatocellular carcinoma: implications for resection beyond the BCLC Guidelines[J]. Ann Surg Oncol 2019.

  16. Huang P Y, Wang C C, Lin C C, et al. Predictive effects of inflammatory scores in patients with BCLC 0-A hepatocellular carcinoma after hepatectomy[J]. J Clin Med. 2019, 8(10).

  17. Vogel A, Cervantes A, Chau I, et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†[J]. Ann Oncol. 2018, 29(Supplement_4): v238-v255.

    Article  Google Scholar 

  18. Kim J Y, Sinn D H, Gwak G Y, et al. Transarterial chemoembolization versus resection for intermediate-stage (BCLC B) hepatocellular carcinoma[J]. Clin Mol Hepatol 2016, 22(2): 250-258.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tada T, Kumada T, Toyoda H, et al. Role of hepatic resection in patients with intermediate-stage hepatocellular carcinoma: a multicenter study from Japan[J]. Cancer Sci 2017, 108(7): 1414-1420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhao Y N, Zhang Y Q, Ye J Z, et al. Hepatic resection versus transarterial chemoembolization for patients with Barcelona Clinic Liver Cancer intermediate stage Child-Pugh A hepatocellular carcinoma[J]. Exp Ther Med 2016, 12(6): 3813-3819.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Liu W, Wang K, Bao Q, et al. Hepatic resection provided long-term survival for patients with intermediate and advanced-stage resectable hepatocellular carcinoma[J]. World J Surg Oncol 2016, 14: 62.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ren Z, Li A, Jiang J, et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma[J]. Gut. 2019, 68(6): 1014-1023.

    Article  CAS  PubMed  Google Scholar 

  23. Yarchoan M, Agarwal P, Villanueva A, et al. Recent developments and therapeutic strategies against hepatocellular carcinoma[J]. Cancer Res 2019, 79(17): 4326-4330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Huang J, Liu F C, Li L, et al. Prognostic nomogram for hepatitis B Virus-related hepatocellular carcinoma with adjuvant transarterial chemoembolization after radical resection[J]. Am J Clin Oncol 2019.

  25. Xie H, Tian S, Cui L, et al. Adjuvant trans-arterial chemoembolization after hepatectomy significantly improves the prognosis of low-risk patients with R0-stage hepatocellular carcinoma[J]. Cancer Manag Res 2019, 11: 4065-4073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lesurtel M, Mullhaupt B, Pestalozzi B C, et al. Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis[J]. Am J Transplant 2006, 6(11): 2644-2650.

    Article  CAS  PubMed  Google Scholar 

  27. Chinese College of Interventionalists. Clinical guideline: effect of transarterial chemoembolization in patient with hepatocellular carcinoma in China [J]. Chin Med J 2018, 98(47): 3811-3819.

    Google Scholar 

  28. Clavien P A, Barkun J, de Oliveira M L, et al. The Clavien-Dindo classification of surgical complications: five-year experience[J]. Ann Surg 2009, 250(2): 187-196.

    Article  PubMed  Google Scholar 

  29. Lee S W, Kwon J H, Lee H L, et al. Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and mortality in treatment-naive patients with chronic hepatitis B in Korea: a large-scale, propensity score analysis[J]. Gut. 2019.

  30. Sun J Y, Yin T, Zhang X Y, et al. Therapeutic advances for patients with intermediate hepatocellular carcinoma[J]. J Cell Physiol 2019, 234(8): 12116-12121.

    Article  CAS  PubMed  Google Scholar 

  31. Wang Y Y, Zhong J H, Xu H F, et al. A modified staging of early and intermediate hepatocellular carcinoma based on single tumour &gt;7 cm and multiple tumours beyond up-to-seven criteria[J]. Aliment Pharmacol Ther 2019, 49(2): 202-210.

    Article  PubMed  Google Scholar 

  32. Yang B, Zheng B, Yang M, et al. Liver resection versus transarterial chemoembolization for the initial treatment of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma[J]. Hepatol Int 2018, 12(5): 417-428.

    Article  PubMed  Google Scholar 

  33. Liu W, Zhou J G, Sun Y, et al. Hepatic resection improved the long-term survival of patients with BCLC stage B hepatocellular carcinoma in Asia: a systematic review and meta-analysis[J]. J Gastrointest Surg 2015, 19(7): 1271-1280.

    Article  PubMed  Google Scholar 

  34. Lin C, Lin C, Lin T, et al. Comparison of surgical resection and transarterial chemoembolization for patients with intermediate stage hepatocellular carcinoma[J]. Journal of Cancer Research and Practice 2016, 3(2): 34-38.

    Article  Google Scholar 

  35. Li J, Hou Y, Cai X, et al. Sorafenib after resection improves the outcome of BCLC stage C hepatocellular carcinoma[J]. World J Gastroenterol 2016, 22(15): 4034-4040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu W, Wang K, Bao Q, et al. Hepatic resection provided long-term survival for patients with intermediate and advanced-stage resectable hepatocellular carcinoma[J]. World Journal of Surgical Oncology. 2016, 14(1).

  37. Bolondi L, Burroughs A, Dufour J, et al. Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions[J]. Semin Liver Dis 2013, 32(04): 348-359.

    Article  CAS  Google Scholar 

  38. Kim J H, Shim J H, Lee H C, et al. New intermediate-stage subclassification for patients with hepatocellular carcinoma treated with transarterial chemoembolization[J]. Liver Int 2017, 37(12): 1861-1868.

    Article  CAS  PubMed  Google Scholar 

  39. Yoo J, Yu S J, Lee B, et al. Appraisal of a model to estimate survival in ambulatory patients with hepatocellular carcinoma classified as Barcelona Clinic Liver Cancer Stage B[J]. Gut and Liver 2019.

  40. Jeong S, Zheng B, Wang J, et al. Transarterial chemoembolization: a favorable postoperative management to improve prognosis of hepatitis B virus-associated intrahepatic cholangiocarcinoma after surgical resection[J]. Int J Biol Sci 2017, 13(10): 1234-1241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang H, Du P, Wu M, et al. Postoperative adjuvant transarterial chemoembolization for multinodular hepatocellular carcinoma within the Barcelona Clinic Liver Cancer early stage and microvascular invasion[J]. HepatoBiliary Surgery and Nutrition 2018, 7(6): 418-428.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wang L, Ke Q, Lin N, et al. Does postoperative adjuvant transarterial chemoembolization benefit for all patients with hepatocellular carcinoma combined with microvascular invasion: a meta-analysis[J]. Scand J Gastroenterol 2019, 54(5): 528-537.

    Article  CAS  PubMed  Google Scholar 

  43. Gao Z, Du G, Pang Y, et al. Adjuvant transarterial chemoembolization after radical resection contributed to the outcomes of hepatocellular carcinoma patients with high-risk factors[J]. Medicine (Baltimore) 2017, 96(33): e7426.

    Article  Google Scholar 

  44. Kuang X, Ye J, Xie Z, et al. Adjuvant transarterial chemoembolization to improve the prognosis of hepatocellular carcinoma following curative resection[J]. Oncol Lett 2018, 16(4): 4937-4944.

    PubMed  PubMed Central  Google Scholar 

  45. Liu S, Li H, Guo L, et al. Tumor size affects efficacy of adjuvant transarterial chemoembolization in patients with hepatocellular carcinoma and microvascular invasion[J]. Oncologist. 2019, 24(4): 513-520.

    Article  CAS  PubMed  Google Scholar 

  46. Wang H, Feng L H, Qian Y W, et al. Does microvascular invasion in Barcelona Clinic Liver Cancer stage A multinodular hepatocellular carcinoma indicate early-stage behavior? [J]. Ann Transl Med 2019, 7(18): 428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pan Y X, Chen J C, Fang A P, et al. A nomogram predicting the recurrence of hepatocellular carcinoma in patients after laparoscopic hepatectomy[J]. Cancer Commun (Lond) 2019, 39(1): 55.

    Article  Google Scholar 

  48. Kimura H, Ohkawa K, Miyazaki M, et al. Subclassification of patients with intermediate-stage (Barcelona Clinic Liver Cancer stage-B) hepatocellular carcinoma using the up-to-seven criteria and serum tumor markers[J]. Hepatol Int 2017, 11(1): 105-114.

    Article  PubMed  Google Scholar 

  49. Wang B, Xia C Y, Lau W Y, et al. Determination of clonal origin of recurrent hepatocellular carcinoma for personalized therapy and outcomes evaluation: a new strategy for hepatic surgery[J]. J Am Coll Surg 2013, 217(6): 1054-1062.

    Article  PubMed  Google Scholar 

  50. Finkelstein S D, Marsh W, Demetris A J, et al. Microdissection-based allelotyping discriminates de novo tumor from intrahepatic spread in hepatocellular carcinoma[J]. Hepatology. 2003, 37(4): 871-879.

    Article  CAS  PubMed  Google Scholar 

  51. Gehrau R, Mas V, Archer K J, et al. Molecular classification and clonal differentiation of hepatocellular carcinoma: the step forward for patient selection for liver transplantation[J]. Expert Rev Gastroenterol Hepatol 2011, 5(4): 539-552.

    Article  CAS  PubMed  Google Scholar 

  52. Yang J D, Ahmed F, Mara K C, et al. Diabetes is associated with increased risk of hepatocellular carcinoma in patients with cirrhosis from nonalcoholic fatty liver disease[J]. Hepatology. 2019.

  53. Shyu Y C, Huang T S, Chien C H, et al. Diabetes poses a higher risk of hepatocellular carcinoma and mortality in patients with chronic hepatitis B: a population-based cohort study[J]. J Viral Hepat 2019, 26(6): 718-726.

    Article  PubMed  Google Scholar 

  54. Zhang Q, Kong J, Dong S, et al. Metformin exhibits the anti-proliferation and anti-invasion effects in hepatocellular carcinoma cells after insufficient radiofrequency ablation[J]. Cancer Cell Int 2017, 17(1): 48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Schulte L, Scheiner B, Voigtländer T, et al. Treatment with metformin is associated with a prolonged survival in patients with hepatocellular carcinoma[J]. Liver Int 2019, 39(4): 714-726.

    Article  CAS  PubMed  Google Scholar 

  56. Wang C P, Kuhn J, Shah D P, et al. Metformin modifies disparity in hepatocellular carcinoma incidence in men with type 2 diabetes but without chronic liver diseases[J]. Cancer Medicine 2019.

  57. de Oliveira S, Houseright R A, Graves A L, et al. Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish[J]. J Hepatol 2019, 70(4): 710-721.

    Article  PubMed  CAS  Google Scholar 

  58. Lee S, Kang T W, Song K D, et al. Effect of microvascular invasion risk on early recurrence of hepatocellular carcinoma after surgery and radiofrequency ablation[J]. Ann Surg 2019.

  59. Malloy P C. Combination therapy in intermediate-stage hepatocellular carcinoma: do we need to know about microvascular invasion?[J]. Radiology. 2019, 292(1): 248-249.

    Article  PubMed  Google Scholar 

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Acknowledgments

NA.

Grant Support

This study was supported by Fujian provincial medical center of hepatobiliary, key Clinical Specialty Discipline Construction Program of Fuzhou (201912002), Science and Technology Project of Fuzhou (Grant number: 2019-SZ-47), and Startup Fund for scientific research, Fujian Medical University (Grant number: 2018QH1195).

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Author notes

  1. Lei Wang, Nanping Lin and Kongying Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian, People’s Republic of China

    Lei Wang

  2. Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian, People’s Republic of China

    Jingfeng Liu

  3. Department of General Surgery, 900th Hospital of PLA, 305 Zhongshan East Road,, Nanjing, Jiangsu Province, China

    Chunhong Xiao

  4. Department of Pediatric Surgery, Huai’an Women and Children’s Hospital, Huai’an, Jiangsu, China

    Ren Wang

  5. Department of Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, China

    Jingbo Chen

  6. The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai, China

    Weiping Zhou

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  1. Lei Wang
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Wang, L., Lin, N., Lin, K. et al. The Clinical Value of Postoperative Transarterial Chemoembolization for Resectable Patients with Intermediate Hepatocellular Carcinoma After Radical Hepatectomy: a Propensity Score-Matching Study. J Gastrointest Surg 25, 1172–1183 (2021). https://doi.org/10.1007/s11605-020-04588-5

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