Advertisement

Annals of Surgical Oncology

, Volume 25, Issue 7, pp 2098–2104 | Cite as

Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus

  • Shuang Liu
  • Lei Guo
  • Hui Li
  • Bo Zhang
  • Jialei Sun
  • Chenghao Zhou
  • Jian Zhou
  • Jia FanEmail author
  • Qinghai YeEmail author
Hepatobiliary Tumors

Abstract

Background

It remains uncertain whether patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) benefit from postoperative adjuvant trans-arterial chemoembolization (PA-TACE).

Methods

We retrospectively identified 540 patients to form the crude cohort and adopted propensity score matching analysis to assemble another cohort of 464 patients with similar baseline characteristics. Univariate and multivariate Cox analyses were performed in exploratory subgroups to identify the independent effect of PA-TACE on overall survival (OS).

Results

In the overall study population, univariate analysis showed PA-TACE was associated with longer OS [odds ratio (OR) = 0.55, p = 0.001], and stratified analyses indicated an interaction between PVTT types and PA-TACE on OS (p = 0.057 for interaction). After matching, all of the characteristics were well balanced between the PA-TACE and control groups (all p > 0.05). Multivariate Cox analysis validated that the protective role of PA-TACE was significant greater with the expansion of PVTT (type I, OR 0.66; type II, OR 0.33; and type III, OR 0.33, respectively, p = 0.011 for interaction). There also was evidence of treatment effect modification by PVTT type in the crude cohort (type I, OR 0.60; type II, OR 0.32; and type III, OR 0.32, respectively, p = 0.011 for interaction).

Conclusions

In patients with HCC and PVTT, PA-TACE was associated with a lower risk of death, particularly, among those with PVTT involving right/left or main portal vein, after excluding patients who were unsuitable for this procedure at 1 month after surgery.

Notes

Acknowledgments

This work was supported in part by grants from Program of Shanghai Subject Chief Scientist (16XD1400800), and the National Natural Science Foundation of China (81572301, 81502487).

Supplementary material

10434_2018_6438_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 347 kb)
10434_2018_6438_MOESM2_ESM.tif (1.2 mb)
Figure S1. Effect of PA-TACE on overall survival in exploratory subgroups. Odds ratio of PA-TACE on overall survival appeared to be different in various PVTT types subgroups (OR 0.68, 0.39 and 0.36, respectively, crude P for interaction = 0.057). In addition, there was no significantly different treatment effect of PA-TACE in any of the remain sub-groups (all, P > 0.05). Supplementary material 2 (TIFF 454 kb)
10434_2018_6438_MOESM3_ESM.tif (343 kb)
Figure S2. Overall survival curves for patients with different types of PVTT in the PS-matched cohort. In the PS-matched cohort, patients with Type III and Type II PVTT had shorter OS than those with Type I (mean survival time 22, 24 and 34 months, respectively, P = 0.001). Supplementary material 3 (TIFF 1233 kb)
10434_2018_6438_MOESM4_ESM.tif (454 kb)
Figure S3. Overall survival curves for patients in the PA-TACE and control groups stratified by PVTT types in the crude cohort. The overall survival of patients who received PA-TACE were significantly lower than those of patients who did not receive PA-TACE in type I PVTT (mean survival time 43 vs. 33 months, P = 0.015, a), type II PVTT (mean survival time 29 vs. 15 months, P < 0.01, b) and type III PVTT (mean survival time 25 vs. 13 months, P < 0.01, c) subgroups. Supplementary material 4 (TIFF 344 kb)

References

  1. 1.
    Liu P-H, Lee Y-H, Hsia C-Y, et al. Surgical resection versus transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis. Ann Surg Oncol. 2014;21(6):1825-33.CrossRefPubMedGoogle Scholar
  2. 2.
    Huang M, Lin Q, Wang H, et al. Survival benefit of chemoembolization plus Iodine125 seed implantation in unresectable hepatitis B-related hepatocellular carcinoma with PVTT: a retrospective matched cohort study. Eur Radiol. 2016;26(10):3428-36.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Cabibbo G, Enea M, Attanasio M, Bruix J, Craxì A, Cammà C. A meta‐analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma. Hepatology. 2010;51(4):1274-83.CrossRefPubMedGoogle Scholar
  4. 4.
    Forner A, Reig ME, De Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Paper presented at seminars in liver disease, 2010.Google Scholar
  5. 5.
    Cheng A-L, Kang Y-K, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25-34.CrossRefPubMedGoogle Scholar
  6. 6.
    Kondo K, Chijiiwa K, Kai M, et al. Surgical strategy for hepatocellular carcinoma patients with portal vein tumor thrombus based on prognostic factors. J Gastrointest Surg. 2009;13(6):1078-83.CrossRefPubMedGoogle Scholar
  7. 7.
    Shi J, Lai EC, Li N, et al. Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. Ann Surg Oncol. 2010;17(8):2073-80.CrossRefPubMedGoogle Scholar
  8. 8.
    Peng Z-W, Guo R-P, Zhang Y-J, Lin X-J, Chen M-S, Lau WY. Hepatic resection versus transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus. Cancer. 2012;118(19):4725-36.CrossRefPubMedGoogle Scholar
  9. 9.
    Yang T, Lin C, Zhai J, et al. Surgical resection for advanced hepatocellular carcinoma according to Barcelona Clinic Liver Cancer (BCLC) staging. J Cancer Res Clin Oncol. 2012;138(7):1121-9.CrossRefPubMedGoogle Scholar
  10. 10.
    Fan J, Zhou J, Wu Z, et al. Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol. 2005;11(8):1215-9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Marelli L, Stigliano R, Triantos C, et al. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Cancer Treat Rev. 2006;32(8):594–606.CrossRefPubMedGoogle Scholar
  12. 12.
    Izumi R, Shimizu K, Iyobe T, et al. Postoperative adjuvant hepatic arterial infusion of lipiodol containing anticancer drugs in patients with hepatocellular carcinoma. Hepatology. 1994;20(2):295–301.CrossRefPubMedGoogle Scholar
  13. 13.
    Lau WY, Lai EC, Leung TW, Simon C. Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial—update on 5-year and 10-year survival. Ann Surg. 2008;247(1):43–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Sun JJ, Wang K, Zhang CZ, et al. Postoperative adjuvant transcatheter arterial chemoembolization after r0 hepatectomy improves outcomes of patients who have hepatocellular carcinoma with microvascular invasion. Ann Surg Oncol. 2015:1–8.Google Scholar
  15. 15.
    Yin J, Bo W, Sun J, et al. New evidence and perspectives on the management of hepatocellular carcinoma with portal vein tumor thrombus. J Clin Transl Hepatol. 2017;5(2):169–76.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Sun H-C, Zhang W, Qin L-X, et al. Positive serum hepatitis B e antigen is associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma. J Hepatol. 2007;47(5):684–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Liu S, Li X, Li H, et al. Longer duration of the Pringle maneuver is associated with hepatocellular carcinoma recurrence following curative resection. J Surg Oncol. 2016;114(1):112–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Edmondson HA, Steiner PE. Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies. Cancer. 1954;7(3):462–503.CrossRefPubMedGoogle Scholar
  19. 19.
    Kikuchi LO, Paranagua-Vezozzo DC, Chagas AL, et al. Nodules less than 20 mm and vascular invasion are predictors of survival in small hepatocellular carcinoma. J Clin Gastroenterol. 2009;43(2):191–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Shi J, Lai EC, Li N, et al. Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. Ann Surg Oncol. 2010;17(8):2073–80.CrossRefPubMedGoogle Scholar
  21. 21.
    Hu H, Han XK, Long XR, et al. Prognostic nomogram for post-surgical treatment with adjuvant TACE in hepatitis B virus-related hepatocellular carcinoma. Oncotarget. Aug 5 2016.Google Scholar
  22. 22.
    Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg. 2000;232(1):10–24.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Cha C, Fong Y, Jarnagin WR, Blumgart LH, DeMatteo RP. Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg. 2003;197(5):753–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol. 1954;30(5):969–77.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Peng B-G, He Q, Li J-P, Zhou F. Adjuvant transcatheter arterial chemoembolization improves efficacy of hepatectomy for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Surg. 2009;198(3):313–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Li Q, Wang J, Sun Y, et al. Efficacy of postoperative transarterial chemoembolization and portal vein chemotherapy for patients with hepatocellular carcinoma complicated by portal vein tumor thrombosis—a randomized study. World J Surg. 2006;30(11):2004–11.CrossRefPubMedGoogle Scholar
  27. 27.
    Li X, Feng GS, Zheng CS, Zhuo CK, Liu X. Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol. 2004;10(19):2878–82.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Tong Y, Li Z, Liang Y, et al. Postoperative adjuvant TACE for patients of hepatocellular carcinoma in AJCC stage I: friend or foe? a propensity score analysis. Oncotarget. 2017;8(16):26671–8.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Zhong C, Guo R-p, Li J-q, et al. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol. 2009;135(10):1437–45.CrossRefPubMedGoogle Scholar
  30. 30.
    Chen X-P, Qiu F-Z, Wu Z-D, et al. Effects of location and extension of portal vein tumor thrombus on long-term outcomes of surgical treatment for hepatocellular carcinoma. Ann Surg Oncol. 2006;13(7):940–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Niu Z-J, Ma Y-L, Kang P, et al. Transarterial chemoembolization compared with conservative treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus: using a new classification. Med Oncol. 2012;29(4):2992-7.CrossRefPubMedGoogle Scholar
  32. 32.
    Shi J, Lai EC, Li N, et al. A new classification for hepatocellular carcinoma with portal vein tumor thrombus. J Hepatobil Pancreat Sci. 2011;18(1):74-80.CrossRefGoogle Scholar
  33. 33.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020-2.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Roayaie S, Frischer JS, Emre SH, et al. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg. 2002;235(4):533-9.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ueno K, Miyazono N, Inoue H, Nishida H, Kanetsuki I, Nakajo M. Transcatheter arterial chemoembolization therapy using iodized oil for patients with unresectable hepatocellular carcinoma: evaluation of three kinds of regimens and analysis of prognostic factors. Cancer. 2000;88(7):1574-81.CrossRefPubMedGoogle Scholar
  36. 36.
    Zhong J-H, Ma L, Li L-Q. Postoperative therapy options for hepatocellular carcinoma. Scand J Gastroenterol. 2014;49(6):649-61.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Shuang Liu
    • 1
    • 2
  • Lei Guo
    • 1
    • 2
  • Hui Li
    • 1
    • 2
  • Bo Zhang
    • 1
    • 2
  • Jialei Sun
    • 1
    • 2
  • Chenghao Zhou
    • 1
    • 2
  • Jian Zhou
    • 1
    • 2
  • Jia Fan
    • 1
    • 2
    Email author
  • Qinghai Ye
    • 1
    • 2
    Email author
  1. 1.Department of Liver Surgery, Liver Cancer Institute and Zhongshan HospitalFudan UniversityShanghaiChina
  2. 2.Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University)Ministry of EducationShanghaiChina

Personalised recommendations