Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

Jia-Zhou Ye, Jun-Ze Chen, Zi-Hui Li, Tao Bai, Jie Chen, Shao-Liang Zhu, Le-Qun Li, Fei-Xiang Wu, Jia-Zhou Ye, Jun-Ze Chen, Zi-Hui Li, Tao Bai, Jie Chen, Shao-Liang Zhu, Le-Qun Li, Fei-Xiang Wu

Abstract

Aim: To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer (BCLC) early (A) and intermediate (B) stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).

Methods: A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival (RFS) and overall survival (OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE.

Results: Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/mL, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/mL, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/mL, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.

Conclusion: PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early- and intermediate-stage HCC patients with MVI.

Keywords: Hepatocellular carcinoma; Microvascular invasion; Overall survival; Postoperative adjuvant transcatheter arterial chemoembolization; Recurrence-free survival.

Conflict of interest statement

Conflict-of-interest statement: The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Overall survival and recurrence-free survival curves of hepatocellular carcinoma patients who either underwent liver resection alone or followed by postoperative adjuvant transcatheter arterial chemoembolization. A: OS for HCC/MVI (-) patients (P = 0.872); B: OS for HCC/MVI (+) patients (P = 0.019); C: RFS for HCC/MVI (-) patients (P = 0.974); D: RFS for HCC/MVI (+) patients (P = 0.002). OS: Overall survival; HCC: Hepatocellular carcinoma; MVI: Microvascular invasion; RFS: Recurrence-free survival.

References

    1. McGuire S. World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr. 2016;7:418–419.
    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.
    1. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107.
    1. Gao JD, Shao YF, Xu Y, Ming LH, Wu ZY, Liu GT, Wang XH, Gao WH, Sun YT, Feng XL, et al. Tight association of hepatocellular carcinoma with HBV infection in North China. Hepatobiliary Pancreat Dis Int. 2005;4:46–49.
    1. Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.
    1. Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology. 2002;35:519–524.
    1. Lim KC, Chow PK, Allen JC, Siddiqui FJ, Chan ES, Tan SB. Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria. Br J Surg. 2012;99:1622–1629.
    1. Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F. Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg. 1991;214:114–117.
    1. European Association For The Study Of The Liver ; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–943.
    1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
    1. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–1474.
    1. Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–338.
    1. Kudo M, Kitano M, Sakurai T, Nishida N. General Rules for the Clinical and Pathological Study of Primary Liver Cancer, Nationwide Follow-Up Survey and Clinical Practice Guidelines: The Outstanding Achievements of the Liver Cancer Study Group of Japan. Dig Dis. 2015;33:765–770.
    1. Gouw AS, Balabaud C, Kusano H, Todo S, Ichida T, Kojiro M. Markers for microvascular invasion in hepatocellular carcinoma: where do we stand? Liver Transpl. 2011;17 Suppl 2:S72–S80.
    1. Rodríguez-Perálvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AK. A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol. 2013;20:325–339.
    1. Roayaie S, Blume IN, Thung SN, Guido M, Fiel MI, Hiotis S, Labow DM, Llovet JM, Schwartz ME. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology. 2009;137:850–855.
    1. Sparrelid E, Del Chiaro M. Microvascular Invasion in Hepatitis B Virus-Related Hepatocellular Carcinoma: Another Step Toward Preoperative Evaluation? JAMA Surg. 2016;151:364.
    1. Du M, Chen L, Zhao J, Tian F, Zeng H, Tan Y, Sun H, Zhou J, Ji Y. Microvascular invasion (MVI) is a poorer prognostic predictor for small hepatocellular carcinoma. BMC Cancer. 2014;14:38.
    1. Lim KC, Chow PK, Allen JC, Chia GS, Lim M, Cheow PC, Chung AY, Ooi LL, Tan SB. Microvascular invasion is a better predictor of tumor recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria. Ann Surg. 2011;254:108–113.
    1. Barreto SG, Brooke-Smith M, Dolan P, Wilson TG, Padbury RT, Chen JW. Cirrhosis and microvascular invasion predict outcomes in hepatocellular carcinoma. ANZ J Surg. 2013;83:331–335.
    1. Ünal E, İdilman İS, Akata D, Özmen MN, Karçaaltıncaba M. Microvascular invasion in hepatocellular carcinoma. Diagn Interv Radiol. 2016;22:125–132.
    1. Faber W, Stockmann M, Kruschke JE, Denecke T, Bahra M, Seehofer D. Implication of microscopic and macroscopic vascular invasion for liver resection in patients with hepatocellular carcinoma. Dig Surg. 2014;31:204–209.
    1. Sun JJ, Wang K, Zhang CZ, Guo WX, Shi J, Cong WM, Wu MC, Lau WY, Cheng SQ. Postoperative Adjuvant Transcatheter Arterial Chemoembolization After R0 Hepatectomy Improves Outcomes of Patients Who have Hepatocellular Carcinoma with Microvascular Invasion. Ann Surg Oncol. 2016;23:1344–1351.
    1. Hirokawa F, Hayashi M, Asakuma M, Shimizu T, Inoue Y, Uchiyama K. Risk factors and patterns of early recurrence after curative hepatectomy for hepatocellular carcinoma. Surg Oncol. 2016;25:24–29.
    1. Sumie S, Kuromatsu R, Okuda K, Ando E, Takata A, Fukushima N, Watanabe Y, Kojiro M, Sata M. Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors. Ann Surg Oncol. 2008;15:1375–1382.
    1. Kanai T, Hirohashi S, Upton MP, Noguchi M, Kishi K, Makuuchi M, Yamasaki S, Hasegawa H, Takayasu K, Moriyama N. Pathology of small hepatocellular carcinoma. A proposal for a new gross classification. Cancer. 1987;60:810–819.
    1. EDMONDSON HA, STEINER PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.
    1. Sumie S, Nakashima O, Okuda K, Kuromatsu R, Kawaguchi A, Nakano M, Satani M, Yamada S, Okamura S, Hori M, et al. The significance of classifying microvascular invasion in patients with hepatocellular carcinoma. Ann Surg Oncol. 2014;21:1002–1009.
    1. Zhong C, Guo RP, Li JQ, Shi M, Wei W, Chen MS, Zhang YQ. 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;135:1437–1445.
    1. Jin YJ, Lee JW, Lee OH, Chung HJ, Kim YS, Lee JI, Cho SG, Jeon YS, Lee KY, Ahn SI, et al. Transarterial chemoembolization versus surgery/radiofrequency ablation for recurrent hepatocellular carcinoma with or without microvascular invasion. J Gastroenterol Hepatol. 2014;29:1056–1064.
    1. Wang SN, Chuang SC, Lee KT. Efficacy of sorafenib as adjuvant therapy to prevent early recurrence of hepatocellular carcinoma after curative surgery: A pilot study. Hepatol Res. 2014;44:523–531.
    1. Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015;16:1344–1354.
    1. Fan J, Zhou J, Wu ZQ, Qiu SJ, Wang XY, Shi YH, Tang ZY. Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol. 2005;11:1215–1219.
    1. Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 2005;25:181–200.
    1. Nagano Y, Shimada H, Takeda K, Ueda M, Matsuo K, Tanaka K, Endo I, Kunisaki C, Togo S. Predictive factors of microvascular invasion in patients with hepatocellular carcinoma larger than 5 cm. World J Surg. 2008;32:2218–2222.
    1. Pawlik TM, Delman KA, Vauthey JN, Nagorney DM, Ng IO, Ikai I, Yamaoka Y, Belghiti J, Lauwers GY, Poon RT, et al. Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl. 2005;11:1086–1092.
    1. Esnaola NF, Lauwers GY, Mirza NQ, Nagorney DM, Doherty D, Ikai I, Yamaoka Y, Regimbeau JM, Belghiti J, Curley SA, et al. Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation. J Gastrointest Surg. 2002;6:224–232; discussion 232.
    1. Jun L, Zhenlin Y, Renyan G, Yizhou W, Xuying W, Feng X, Yong X, Kui W, Jian L, Dong W, et al. Independent factors and predictive score for extrahepatic metastasis of hepatocellular carcinoma following curative hepatectomy. Oncologist. 2012;17:963–969.
    1. Lu XY, Xi T, Lau WY, Dong H, Xian ZH, Yu H, Zhu Z, Shen F, Wu MC, Cong WM. Pathobiological features of small hepatocellular carcinoma: correlation between tumor size and biological behavior. J Cancer Res Clin Oncol. 2011;137:567–575.
    1. Groeschl RT, Gamblin TC, Turaga KK. Ablation for hepatocellular carcinoma: validating the 3-cm breakpoint. Ann Surg Oncol. 2013;20:3591–3595.
    1. Chandarana H, Robinson E, Hajdu CH, Drozhinin L, Babb JS, Taouli B. Microvascular invasion in hepatocellular carcinoma: is it predictable with pretransplant MRI? AJR Am J Roentgenol. 2011;196:1083–1089.
    1. Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, Giulini SM. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006;243:229–235.
    1. Cucchetti A, Piscaglia F, Caturelli E, Benvegnù L, Vivarelli M, Ercolani G, Cescon M, Ravaioli M, Grazi GL, Bolondi L, et al. Comparison of recurrence of hepatocellular carcinoma after resection in patients with cirrhosis to its occurrence in a surveilled cirrhotic population. Ann Surg Oncol. 2009;16:413–422.
    1. Wang J, Li Q, Sun Y, Zheng H, Cui Y, Li H, Zhou H, Hao X. Clinicopathologic features between multicentric occurence and intrahepatic metastasis of multiple hepatocellular carcinomas related to HBV. Surg Oncol. 2009;18:25–30.
    1. Inayoshi J, Ichida T, Sugitani S, Tsuboi Y, Genda T, Honma N, Asakura H. Gross appearance of hepatocellular carcinoma reflects E-cadherin expression and risk of early recurrence after surgical treatment. J Gastroenterol Hepatol. 2003;18:673–677.
    1. Iguchi T, Aishima S, Sanefuji K, Fujita N, Sugimachi K, Gion T, Taketomi A, Shirabe K, Maehara Y, Tsuneyoshi M. Both fibrous capsule formation and extracapsular penetration are powerful predictors of poor survival in human hepatocellular carcinoma: a histological assessment of 365 patients in Japan. Ann Surg Oncol. 2009;16:2539–2546.
    1. Ng IO, Lai EC, Ng MM, Fan ST. Tumor encapsulation in hepatocellular carcinoma. A pathologic study of 189 cases. Cancer. 1992;70:45–49.

Source: PubMed

3
Iratkozz fel