Recurrence Patterns and Disease-Free Survival after Resection of Intrahepatic Cholangiocarcinoma: Preoperative and Postoperative Prognostic Models

Alexandre Doussot, Mithat Gonen, Jimme K Wiggers, Bas Groot-Koerkamp, Ronald P DeMatteo, David Fuks, Peter J Allen, Olivier Farges, T Peter Kingham, Jean Marc Regimbeau, Michael I D'Angelica, Daniel Azoulay, William R Jarnagin, Alexandre Doussot, Mithat Gonen, Jimme K Wiggers, Bas Groot-Koerkamp, Ronald P DeMatteo, David Fuks, Peter J Allen, Olivier Farges, T Peter Kingham, Jean Marc Regimbeau, Michael I D'Angelica, Daniel Azoulay, William R Jarnagin

Abstract

Background: Liver resection is the most effective treatment for intrahepatic cholangiocarcinoma. Recurrent disease is frequent; however, recurrence patterns are ill-defined and prognostic models are lacking.

Study design: A primary cohort of 189 patients who underwent resection for intrahepatic cholangiocarcinoma was used for recurrence patterns analysis within and after 24 months. Based on independent factors for disease-free survival identified in Cox regression analysis, preoperative and postoperative models were developed using a recursive partitioning method. Models were externally validated using a multicenter cohort of 522 resected patients (Association Française de Chirurgie intrahepatic cholangiocarcinoma study group).

Results: Recurrence within 24 months most often involved the liver (82.7%), and most recurrences after 24 months were strictly extrahepatic (61.1%). In multivariable analysis of the primary cohort, independent preoperative factors for disease-free survival were tumor size and multifocality (based on imaging); tumor size, multifocality, vascular invasion, and lymph node metastases (based on pathology) were independent postoperative factors. The preoperative model allowed patient classification into low-risk and high-risk groups for recurrence. In the validation cohort (n = 522), high-risk patients had a greater likelihood of recurrence (hazard ratio = 2.17; 95% CI, 1.74-2.72; p < 0.001). The postoperative model included tumor size, vascular invasion, and positive nodal disease on pathology and classified patients in low-, intermediate-, and high-risk groups in the primary cohort. As compared with low-risk patients in the validation cohort, intermediate- and high-risk patients were more likely to experience recurrence (hazard ratio = 1.9; 95% CI, 1.41-2.47; p < 0.001 and hazard ratio = 2.99; 95% CI, 2.08-4.31; p < 0.001, respectively).

Conclusions: Recurrence patterns are time dependent. Both models as developed and validated in this study classified patients in distinct recurrence risk groups, which can guide treatment recommendations.

Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Kaplan-Meier survival curves for (A) all patients included (n=189) and (B) recurrence patterns for patients categorized by their disease-free survival. Fifty two patients have not recurred at last follow-up. Dotted line, overall survival (OS) curve; black line, disease-free survival (DFS) curve. (In each group, the proportion of patients experiencing each recurrence patterns is labeled on each corresponding bar).
Figure 2
Figure 2
Recurrence management according to the recurrence patterns. *Patients may have undergone more than 2 different treatment modalities as multimodal therapy.
Figure 3
Figure 3
Preoperative model classifying patients into (A) recurrence risk groups, and Kaplan-Meier estimates of disease-free survival for patients stratified by groups in the (B) primary cohort and (C) validation cohort.
Figure 4
Figure 4
Postoperative model classifying patients into (A) recurrence risk groups, and Kaplan-Meier estimates of disease-free survival for patients stratified by groups in the (B) primary cohort and (C) validation cohort.
Figure 5
Figure 5
Kaplan-Meier estimates of disease-free survival for patients who underwent portal lymphadenectomy classified using the postoperative model in (A) the primary cohort and (B) the validation cohort.

References

    1. Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol. 2004;40:472–477.
    1. Blechacz B, Gores GJ. Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatol. 2008;48:308–321.
    1. De Jong MC, Nathan H, Sotiropoulos GC, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29:3140–3145.
    1. Farges O, Fuks D, Le Treut Y-P, et al. AJCC 7th edition of TNM staging accurately discriminates outcomes of patients with resectable intrahepatic cholangiocarcinoma: By the AFC-IHCC-2009 study group. Cancer. 2011;117:2170–2177.
    1. Ribero D, Pinna AD, Guglielmi A, et al. Surgical approach for long-term survival of patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis of 434 patients. Arch Surg. 2012;147:1107–1113.
    1. Wang Y, Li J, Xia Y, et al. Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy. J Clin Oncol. 2013;31:1188–1195.
    1. Benson AB, Abrams TA, Ben-Josef E, et al. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Cancer Netw. 2009;7:350–391.
    1. Endo I, Gonen M, Yopp AC, et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg. 2008;248:84–96.
    1. Hyder O, Hatzaras I, Sotiropoulos GC, et al. Recurrence after operative management of intrahepatic cholangiocarcinoma. Surgery. 2013;153:811–818.
    1. Tabrizian P, Jibara G, Hechtman JF, et al. Outcomes following resection of intrahepatic cholangiocarcinoma. HPB. 2015;17:344–351.
    1. Jarnagin WR, Schwartz LH, Gultekin DH, et al. Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. Ann Oncol. 2009;20:1589–1595.
    1. Konstantinidis IT, Do RKG, Gultekin DH, et al. Regional chemotherapy for unresectable intrahepatic cholangiocarcinoma: a potential role for dynamic magnetic resonance imaging as an imaging biomarker and a survival update from two prospective clinical trials. Ann Surg Oncol. 2014;21:2675–2683.
    1. Al-Adra DP, Gill RS, Axford SJ, et al. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: A systematic review and pooled analysis. Eur J Surg Oncol. 2015;41:120–127.
    1. Boehm LM, Jayakrishnan TT, Miura JT, et al. Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma. J Surg Oncol. 2015;111:213–220.
    1. Kato A, Shimizu H, Ohtsuka M, et al. Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study. Ann Surg Oncol. 2013;20:318–324.
    1. Ghiringhelli F, Lorgis V, Vincent J, et al. Hepatic arterial infusion of gemcitabine plus oxaliplatin as second-line treatment for locally advanced intrahepatic cholangiocarcinoma: preliminary experience. Chemotherapy. 2013;59:354–360.
    1. Rayar M, Sulpice L, Edeline J, et al. Intra-arterial Yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment. Ann Surg Oncol. 2015;22:3102–3108.
    1. Kingham TP, Correa-Gallego C, D’Angelica MI, et al. Hepatic parenchymal preservation surgery: decreasing morbidity and mortality rates in 4,152 resections for malignancy. J Am Coll Surg. 2015;220:471–479.
    1. Mayo SC, Shore AD, Nathan H, et al. Refining the definition of perioperative mortality following hepatectomy using death within 90 days as the standard criterion. HPB. 2011;13:473–482.
    1. Farges O, Fuks D, Boleslawski E, et al. Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group. Ann Surg. 2011;254:824–829. discussion 830.
    1. Okabayashi T, Yamamoto J, Kosuge T, et al. A new staging system for mass-forming intrahepatic cholangiocarcinoma: analysis of preoperative and postoperative variables. Cancer. 2001;92:2374–2383.
    1. Yamasaki S. Intrahepatic cholangiocarcinoma: macroscopic type and stage classification. J Hepatobiliary Pancreat Surg. 2003;10:288–291.
    1. Edge SB, editor. AJCC cancer staging manual. 7. New York: Springer; 2010. American Joint Committee on Cancer.
    1. Spolverato G, Kim Y, Alexandrescu S, et al. Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative-intent surgical resection. Ann Surg Oncol. 2016;23:235–243.
    1. Doussot A, Groot-Koerkamp B, Wiggers JK, et al. Outcomes after resection of intrahepatic cholangiocarcinoma: external validation and comparison of prognostic models. J Am Coll Surg. 2015;221:452–461.
    1. Breiman L. Classification and regression trees. New York, N.Y: Chapman & Hall; 1993.
    1. Chambers JM, Hastie T, editors. Wadsworth & Brooks/Cole computer science series. Pacific Grove, Calif: Wadsworth & Brooks/Cole Advanced Books & Software; 1992. Statistical models in S.
    1. Nathan H, Aloia TA, Vauthey J-N, et al. A proposed staging system for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009;16:14–22.
    1. Greene FL, editor. American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging handbook: from the AJCC cancer staging manual. 6. New York: Springer; 2002.
    1. Jiang W, Zeng Z-C, Tang Z-Y, et al. A prognostic scoring system based on clinical features of intrahepatic cholangiocarcinoma: the Fudan score. Ann Oncol. 2011;22:1644–1652.
    1. Hyder O, Marques H, Pulitano C, et al. A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience. JAMA Surg. 2014;149:432–438.
    1. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383:2168–2179.
    1. Weber SM, Ribero D, O’Reilly EM, et al. Intrahepatic cholangiocarcinoma: expert consensus statement. HPB. 2015;17:669–680.
    1. Gemcitabine Hydrochloride and Oxaliplatin or Observation in Treating Patients With Biliary Tract Cancer That Has Been Removed by Surgery. [Accessed on line, 02/27/15]; .
    1. Hepatic Arterial Infusion With Floxuridine and Dexamethasone in Combination With Gemcitabine as Adjuvant Treatment After Resection of Intrahepatic Cholangiocarcinoma. [Accessed on line, 02/27/15]; .
    1. Zhang S-J, Hu P, Wang N, et al. Thermal ablation versus repeated hepatic resection for recurrent intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2013;20:3596–3602.
    1. Sulpice L, Rayar M, Boucher E, et al. Treatment of recurrent intrahepatic cholangiocarcinoma. Br J Surg. 2012;99:1711–1717.
    1. Kamphues C, Seehofer D, Collettini F, et al. Preliminary experience with CT-guided high-dose rate brachytherapy as an alternative treatment for hepatic recurrence of cholangiocarcinoma. HPB. 2012;14:791–797.
    1. Takahashi Y, Ebata T, Yokoyama Y, et al. Surgery for recurrent biliary tract cancer: a single-center experience with 74 consecutive resections. Ann Surg. 2014;99:1711–1717.

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