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The role of adjuvant therapy after R0 resection for patients with intrahepatic and perihilar cholangiocarcinomas

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Abstract

Purpose

There is still debated regarding the optimal treatment strategy for cholangiocarcinoma (CC) after curative resection. The aim of this study was to analyze the role of adjuvant therapy in R0-resected intrahepatic and perihilar CCs.

Methods

We retrospectively reviewed the patients who underwent R0 resection for intrahepatic and perihilar CCs between January 2001 and December 2013 at six tertiary medical centers; adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). The outcomes of our study were recurrence-free survival (RFS) and overall survival (OS).

Results

We included a total of 137 consecutive patients in the analysis; 58.4% of them had intrahepatic CCs, and 25.5% had lymph node (LN) involvement. Seventy-three patients (53.3%) had received adjuvant therapy (CT, CRT, RT: 48, 13, 12, respectively), and most patients who had received adjuvant therapy had stage III or IVA, T3 or 4 tumors, and positive LNs. Multivariable analysis identified positive LN [hazard ratio (HR) 3.47; P < 0.001] and high baseline CA 19-9 level (HR 1.82; P = 0.027) as predictors of decreased OS. The effects of adjuvant therapy varied according to the treatment modality; adjuvant CRT showed significantly longer RFS than surgery only (HR 0.44; P = 0.036), with a nonsignificant trend for better OS (HR 0.46; P = 0.115).

Conclusions

Adjuvant CT and RT were not associated with a survival advantage in R0-resected intrahepatic and perihilar CCs. CRT appears to be appropriate treatment after complete resection.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29

    Article  PubMed  Google Scholar 

  2. Shin HR, Oh JK, Masuyer E, Curado MP, Bouvard V, Fang Y, Wiangnon S, Sripa B, Hong ST (2010) Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma–focus on East and South-Eastern Asia. Asian Pac J Cancer Prev 11:1159–1166

    PubMed  Google Scholar 

  3. Anderson CD, Pinson CW, Berlin J, Chari RS (2004) Diagnosis and treatment of cholangiocarcinoma. Oncologist 9:43–57

    Article  PubMed  Google Scholar 

  4. Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G, Iacono C (2009) Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg 33:1247–1254

    Article  PubMed  Google Scholar 

  5. Mao ZY, Guo XC, Su D, Wang LJ, Zhang TT, Bai L (2015) Prognostic factors of cholangiocarcinoma after surgical resection: a retrospective study of 293 patients. Med Sci Monit 21:2375–2381

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nakeeb A, Pitt HA (2005) Radiation therapy, chemotherapy and chemoradiation in hilar cholangiocarcinoma. HPB (Oxford) 7:278–282

    Article  Google Scholar 

  7. Williams TM, Majithia L, Wang SJ, Thomas CR Jr (2014) Defining the role of adjuvant therapy: cholangiocarcinoma and gall bladder cancer. Semin Radiat Oncol 24:94–104

    Article  PubMed  Google Scholar 

  8. Horgan AM, Amir E, Walter T, Knox JJ (2012) Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol 30:1934–1940

    Article  PubMed  Google Scholar 

  9. Nakeeb A, Pitt HA, Sohn TA, Coleman J, Abrams RA, Piantadosi S, Hruban RH, Lillemoe KD, Yeo CJ, Cameron JL (1996) Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 224:463–473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Endo I, Gonen M, Yopp AC, Dalal KM, Zhou Q, Klimstra D, D’Angelica M, DeMatteo RP, Fong Y, Schwartz L, Kemeny N, O’Reilly E, Abou-Alfa GK, Shimada H, Blumgart LH, Jarnagin WR (2008) Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg 248:84–96

    Article  PubMed  Google Scholar 

  11. Nuzzo G, Giuliante F, Ardito F, Giovannini I, Aldrighetti L, Belli G, Bresadola F, Calise F, Dalla Valle R, D’Amico DF, Gennari L, Giulini SM, Guglielmi A, Jovine E, Pellicci R, Pernthaler H, Pinna AD, Puleo S, Torzilli G, Capussotti L, Cillo U, Ercolani G, Ferrucci M, Mastrangelo L, Portolani N, Pulitano C, Ribero D, Ruzzenente A, Scuderi V, Federico B (2012) Improvement in perioperative and long-term outcome after surgical treatment of hilar cholangiocarcinoma: results of an Italian multicenter analysis of 440 patients. Arch Surg 147:26–34

    Article  PubMed  Google Scholar 

  12. Gil E, Joh JW, Park HC, Yu JI, Jung SH, Kim JM (2015) Predictors and patterns of recurrence after curative liver resection in intrahepatic cholangiocarcinoma, for application of postoperative radiotherapy: a retrospective study. World J Surg Oncol 13:227

    Article  PubMed  PubMed Central  Google Scholar 

  13. Groot Koerkamp B, Wiggers JK, Allen PJ, Besselink MG, Blumgart LH, Busch OR, Coelen RJ, D’Angelica MI, DeMatteo RP, Gouma DJ, Kingham TP, Jarnagin WR, van Gulik TM (2015) Recurrence rate and pattern of perihilar cholangiocarcinoma after curative intent resection. J Am Coll Surg 221:1041–1049

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sur MD, In H, Sharpe SM, Baker MS, Weichselbaum RR, Talamonti MS, Posner MC (2015) Defining the benefit of adjuvant therapy following resection for intrahepatic cholangiocarcinoma. Ann Surg Oncol 22:2209–2217

    Article  PubMed  Google Scholar 

  15. Miura JT, Johnston FM, Tsai S, George B, Thomas J, Eastwood D, Banerjee A, Christians KK, Turaga KK, Pawlik TM, Clark Gamblin T (2015) Chemotherapy for surgically resected intrahepatic cholangiocarcinoma. Ann Surg Oncol 22:3716–3723

    Article  PubMed  Google Scholar 

  16. Valle JW, Furuse J, Jitlal M, Beare S, Mizuno N, Wasan H, Bridgewater J, Okusaka T (2014) Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials. Ann Oncol 25:391–398

    Article  CAS  PubMed  Google Scholar 

  17. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Sakabe R, Ohge H, Sueda T (2011) Prognostic factors after surgical resection for intrahepatic, hilar, and distal cholangiocarcinoma. Ann Surg Oncol 18:651–658

    Article  PubMed  Google Scholar 

  18. Eckel F, Schmid RM (2007) Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer 96:896–902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362:1273–1281

    Article  CAS  PubMed  Google Scholar 

  20. Jarnagin WR, Ruo L, Little SA, Klimstra D, D’Angelica M, DeMatteo RP, Wagman R, Blumgart LH, Fong Y (2003) Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer 98:1689–1700

    Article  PubMed  Google Scholar 

  21. Ben-Josef E, Guthrie KA, El-Khoueiry AB, Corless CL, Zalupski MM, Lowy AM, Thomas CR Jr, Alberts SR, Dawson LA, Micetich KC, Thomas MB, Siegel AB, Blanke CD (2015) SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol 33:2617–2622

    Article  CAS  PubMed  Google Scholar 

  22. Kelley RK, Bardeesy N (2015) Biliary tract cancers: finding better ways to lump and split. J Clin Oncol 33:2588–2590

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This paper was supported by the Dong-a University Research Fund.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea

    Young Saing Kim & Inkeun Park

  2. Department of Internal Medicine, Dong-a University College of Medicine, 26 Daeshingongwonro, Seo-gu, Busan, 49201, Republic of Korea

    Sung Yong Oh

  3. Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea

    Se-Il Go, Jung-Hun Kang & Haa-Na Song

  4. Division of Hematology-Oncology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea

    Jun Ho Ji

  5. Division of Hematology/Oncology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea

    In Gyu Hwang & Joung-Soon Jang

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  1. Young Saing Kim
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Correspondence to Sung Yong Oh.

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Kim, Y.S., Oh, S.Y., Go, SI. et al. The role of adjuvant therapy after R0 resection for patients with intrahepatic and perihilar cholangiocarcinomas. Cancer Chemother Pharmacol 79, 99–106 (2017). https://doi.org/10.1007/s00280-016-3206-4

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  • DOI: https://doi.org/10.1007/s00280-016-3206-4

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