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Survival Benefit Relative to Treatment Modalities Among Patients with Very Early Intrahepatic Cholangiocarcinoma: an Analysis of the National Cancer Database

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Journal of Gastrointestinal Surgery

Abstract

Background

Liver transplantation (LT) has been considered a potential curative treatment for patients with very early intrahepatic cholangiocarcinoma (ICC) and cirrhosis, yet the survival benefit of LT has not been well defined. This study aimed to compare the long-term survival outcomes of patients who underwent LT with that of individuals who received resection and non-curative intent treatment (non-CIT).

Methods

Patients who underwent LT, hepatectomy, and non-CIT between 2004 and 2018 were included in the National Cancer Database. Survival benefits of LT over resection and non-CIT were analyzed relative to overall survival (OS).

Results

Among 863 patients, 54 (6.3%) underwent LT, while 342 (39.6%) underwent surgical resection, and 467 (54.1%) received non-CIT, respectively. While the rates of non-CIT increased over time, the percentages of LT remained consistent during the study period. LT patients had similar 5-year OS to individuals who underwent resection (referent, resection: LT, HR 0.95, 95%CI 0.84–1.58, p=0.84). In contrast, 5-year OS was better among patients who underwent LT versus individuals who had non-CIT after controlling other variables using propensity score overlapping weighting (5-year OS, LT 57.1% vs. LR 25.8%, p<0.001).

Conclusions

The outcomes of very early ICC patients who underwent LT were similar to individuals who underwent hepatectomy, but better than patients treated with non-CIT. LT should be may be a consideration as a treatment option for patients with early stage ICC who are unsuitable candidates for resection.

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References

  1. Singal AK, Vauthey JN, Grady JJ, Stroehlein JR. Intra-hepatic cholangiocarcinoma--frequency and demographic patterns: thirty-year data from the M.D. Anderson Cancer Center. J Cancer Res Clin Oncol. 2011;137(7):1071-8. https://doi.org/10.1007/s00432-010-0971-z.

    Article  PubMed  Google Scholar 

  2. Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC. Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol. 2002;37(6):806-13. https://doi.org/10.1016/s0168-8278(02)00297-0.

    Article  PubMed  Google Scholar 

  3. Lima HA, Moazzam Z, Endo Y, Alaimo L, Diaz A, Woldesenbet S et al. Impact of the Affordable Care Act on Presentation, Treatment, and Outcomes of Intrahepatic Cholangiocarcinoma. J Gastrointest Surg. 2022. https://doi.org/10.1007/s11605-022-05496-6.

  4. Palmer WC, Patel T. Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma. J Hepatol. 2012;57(1):69-76. https://doi.org/10.1016/j.jhep.2012.02.022.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kubo S, Shinkawa H, Asaoka Y, Ioka T, Igaki H, Izumi N et al. Liver Cancer Study Group of Japan Clinical Practice Guidelines for Intrahepatic Cholangiocarcinoma. Liver Cancer. 2022;11(4):290-314. https://doi.org/10.1159/000522403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29(23):3140-5. https://doi.org/10.1200/JCO.2011.35.6519.

    Article  PubMed  Google Scholar 

  7. Alaimo L, Endo Y, Lima HA, Moazzam Z, Shaikh CF, Ruzzenente A et al. A comprehensive preoperative predictive score for post-hepatectomy liver failure after hepatocellular carcinoma resection based on patient comorbidities, tumor burden, and liver function: the CTF score. J Gastrointest Surg. 2022;26:2486–95. https://doi.org/10.1007/s11605-022-05451-5.

    Article  PubMed  Google Scholar 

  8. Thakral N, Gonzalez T, Nano O, Shin SH, Samuels S, Hussein A. Cirrhosis in intrahepatic cholangiocarcinoma: prognostic importance and impact on survival. BMC gastroenterology. 2023;23(1):151. https://doi.org/10.1186/s12876-023-02710-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sapisochin G, Rodriguez de Lope C, Gastaca M, Ortiz de Urbina J, Suarez MA, Santoyo J et al. "Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients? Am J Transplant. 2014;14(3):660-7. https://doi.org/10.1111/ajt.12591.

    Article  CAS  PubMed  Google Scholar 

  10. Eguchi S, Hidaka M, Hara T, Matsushima H, Soyama A. Liver transplantation for intrahepatic and hilar cholangiocellular carcinoma: Most recent updates in the literature. Ann Gastroenterol Surg. 2022;6(5):616-22. https://doi.org/10.1002/ags3.12567.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Pichlmayr R, Weimann A, Tusch G, Schlitt HJ. Indications and Role of Liver Transplantation for Malignant Tumors. Oncologist. 1997;2(3):164-70.

    Article  CAS  PubMed  Google Scholar 

  12. Hara T, Eguchi S, Yoshizumi T, Akamatsu N, Kaido T, Hamada T et al. Incidental intrahepatic cholangiocarcinoma in patients undergoing liver transplantation: A multi-center study in Japan. J Hepatobiliary Pancreat Sci. 2021;28(4):346-52. https://doi.org/10.1002/jhbp.896.

    Article  PubMed  Google Scholar 

  13. Ziogas IA, Giannis D, Economopoulos KP, Hayat MH, Montenovo MI, Matsuoka LK et al. Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Meta-analysis and Meta-regression of Survival Rates. Transplantation. 2021;105(10):2263-71. https://doi.org/10.1097/TP.0000000000003539.

    Article  CAS  PubMed  Google Scholar 

  14. Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1):35-43. https://doi.org/10.1016/s1470-2045(08)70284-5.

    Article  PubMed  Google Scholar 

  15. Hue JJ, Rocha FG, Ammori JB, Hardacre JM, Rothermel LD, Chavin KD et al. A comparison of surgical resection and liver transplantation in the treatment of intrahepatic cholangiocarcinoma in the era of modern chemotherapy: An analysis of the National Cancer Database. J Surg Oncol. 2021;123(4):949-56. https://doi.org/10.1002/jso.26370.

    Article  PubMed  Google Scholar 

  16. Lee YT, Singal AG, Lauzon M, Agopian VG, Luu M, Noureddin M et al. Disparities in curative treatments and outcomes for early stage intrahepatic cholangiocarcinoma in the United States. Cancer. 2022;128(20):3610-9. https://doi.org/10.1002/cncr.34436.

    Article  CAS  PubMed  Google Scholar 

  17. De Martin E, Rayar M, Golse N, Dupeux M, Gelli M, Gnemmi V et al. Analysis of Liver Resection Versus Liver Transplantation on Outcome of Small Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma in the Setting of Cirrhosis. Liver Transpl. 2020;26(6):785-98. https://doi.org/10.1002/lt.25737.

    Article  PubMed  Google Scholar 

  18. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-9. https://doi.org/10.3322/caac.21388.

    Article  PubMed  Google Scholar 

  19. Valle JW, Wasan H, Johnson P, Jones E, Dixon L, Swindell R et al. Gemcitabine alone or in combination with cisplatin in patients with advanced or metastatic cholangiocarcinomas or other biliary tract tumours: a multicentre randomised phase II study - The UK ABC-01 Study. Br J Cancer. 2009;101(4):621-7. https://doi.org/10.1038/sj.bjc.6605211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Aalen OO. A linear regression model for the analysis of life times. Stat Med. 1989;8(8):907-25. https://doi.org/10.1002/sim.4780080803.

    Article  CAS  PubMed  Google Scholar 

  21. Hieke S, Kleber M, Konig C, Engelhardt M, Schumacher M. Conditional Survival: A Useful Concept to Provide Information on How Prognosis Evolves over Time. Clin Cancer Res. 2015;21(7):1530-6. https://doi.org/10.1158/1078-0432.CCR-14-2154.

    Article  PubMed  Google Scholar 

  22. Li F, Thomas LE, Li F. Addressing Extreme Propensity Scores via the Overlap Weights. Am J Epidemiol. 2019;188(1):250-7. https://doi.org/10.1093/aje/kwy201.

    Article  PubMed  Google Scholar 

  23. Burnand B, Kernan WN, Feinstein AR. Indexes and boundaries for "quantitative significance" in statistical decisions. J Clin Epidemiol. 1990;43(12):1273-84. https://doi.org/10.1016/0895-4356(90)90093-5.

    Article  CAS  PubMed  Google Scholar 

  24. Quaresima S, Melandro F, Giovanardi F, Shah K, De Peppo V, Mennini G et al. New Insights in the Setting of Transplant Oncology. Medicina (Kaunas). 2023;59(3). https://doi.org/10.3390/medicina59030568.

  25. Rosen CB, Heimbach JK, Gores GJ. Liver transplantation for cholangiocarcinoma. Transpl Int. 2010;23(7):692-7. https://doi.org/10.1111/j.1432-2277.2010.01108.x.

    Article  PubMed  Google Scholar 

  26. Becker NS, Rodriguez JA, Barshes NR, O'Mahony CA, Goss JA, Aloia TA. Outcomes analysis for 280 patients with cholangiocarcinoma treated with liver transplantation over an 18-year period. J Gastrointest Surg. 2008;12(1):117-22. https://doi.org/10.1007/s11605-007-0335-4.

    Article  PubMed  Google Scholar 

  27. Sapisochin G, Facciuto M, Rubbia-Brandt L, Marti J, Mehta N, Yao FY et al. Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment. Hepatology. 2016;64(4):1178-88. https://doi.org/10.1002/hep.28744.

    Article  CAS  PubMed  Google Scholar 

  28. Sapisochin G, Ivanics T, Heimbach J. Liver Transplantation for Intrahepatic Cholangiocarcinoma: Ready for Prime Time? Hepatology. 2022;75(2):455-72. https://doi.org/10.1002/hep.32258.

    Article  PubMed  Google Scholar 

  29. Hong JC, Jones CM, Duffy JP, Petrowsky H, Farmer DG, French S et al. Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: a 24-year experience in a single center. Arch Surg. 2011;146(6):683-9. https://doi.org/10.1001/archsurg.2011.116.

    Article  PubMed  Google Scholar 

  30. Jesper D, Heyn SG, Schellhaas B, Pfeifer L, Goertz RS, Zopf S et al. Effects of liver cirrhosis and patient condition on clinical outcomes in intrahepatic cholangiocarcinoma: a retrospective analysis of 156 cases in a single center. Eur J Gastroenterol Hepatol. 2018;30(5):552-6. https://doi.org/10.1097/MEG.0000000000001036.

    Article  PubMed  Google Scholar 

  31. Mauro E, Ferrer-Fabrega J, Sauri T, Soler A, Cobo A, Burrel M et al. New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy. Cancers (Basel). 2023;15(4). https://doi.org/10.3390/cancers15041244.

  32. Endo Y, Sasaki K, Moazzam Z, Woldesenbet S, Yang J, Lima HA et al. The Impact of a Liver Transplant Program on the Outcomes of Hepatocellular Carcinoma. Ann Surg. 2023. https://doi.org/10.1097/SLA.0000000000005849.

  33. Flemming JA, Muaddi H, Djerboua M, Neves P, Sapisochin G, Selzner N. Association between social determinants of health and rates of liver transplantation in individuals with cirrhosis. Hepatology. 2022;76(4):1079-89. https://doi.org/10.1002/hep.32469.

    Article  CAS  PubMed  Google Scholar 

  34. Chan NW, Moya-Mendez M, Henson JB, Zaribafzadeh H, Sendak MP, Bhavsar NA et al. Social determinants of health data in solid organ transplantation: National data sources and future directions. Am J Transplant. 2022;22(10):2293-301. https://doi.org/10.1111/ajt.17096.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Tovoli F, Guerra P, Iavarone M, Veronese L, Renzulli M, De Lorenzo S et al. Surveillance for Hepatocellular Carcinoma Also Improves Survival of Incidentally Detected Intrahepatic Cholangiocarcinoma Arisen in Liver Cirrhosis. Liver Cancer. 2020;9(6):744-55. https://doi.org/10.1159/000509059.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Weber SM, Ribero D, O'Reilly EM, Kokudo N, Miyazaki M, Pawlik TM. Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015;17(8):669-80. https://doi.org/10.1111/hpb.12441.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Quillin RC, 3rd, Wilson GC, Wima K, Hohmann SF, Sutton JM, Shaw JJ et al. Neighborhood level effects of socioeconomic status on liver transplant selection and recipient survival. Clin Gastroenterol Hepatol. 2014;12(11):1934-41. https://doi.org/10.1016/j.cgh.2014.05.020.

    Article  PubMed  Google Scholar 

  38. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL-ILCA Clinical Practice Guidelines on Intrahepatic Cholangiocarcinoma. J Hepatol. 2023. https://doi.org/10.1016/j.jhep.2023.03.010.

  39. Biliary tract cancer. 2023. https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf.

  40. Simoneau E, D'Angelica M, Halazun KJ. Liver transplantation for colorectal liver metastasis. Curr Opin Organ Transplant. 2019;24(2):175-81. https://doi.org/10.1097/MOT.0000000000000623.

    Article  PubMed  Google Scholar 

  41. Cross-Najafi AA, Lopez K, Isidan A, Park Y, Zhang W, Li P et al. Current Barriers to Clinical Liver Xenotransplantation. Front Immunol. 2022;13:827535. https://doi.org/10.3389/fimmu.2022.827535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Menahem B, Lubrano J, Duvoux C, Mulliri A, Alves A, Costentin C et al. Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat: An attempt to perform an ideal meta-analysis. Liver Transpl. 2017;23(6):836-44. https://doi.org/10.1002/lt.24758.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA

    Yutaka Endo, Muhammad Musaab Munir, Selamawit Woldesenbet, Vivian Resende, Karol Rawicz-Pruszyński, Usama Waqar, Parit Mavani, Erryk Katayama, Jason Yang, Mujtaba Khalil, Muhammad Muntazir Mehdi Khan & Timothy M. Pawlik

  2. Department of Surgery, Stanford University, Palo Alto, CA, USA

    Kazunari Sasaki

  3. Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil

    Vivian Resende

  4. Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland

    Karol Rawicz-Pruszyński

  5. Department of Surgery, Keio University, Tokyo, Japan

    Minoru Kitago

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  1. Yutaka Endo
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Supplementary file 1

Supplementary figure 1: Kaplan-Meier curve for liver transplantation and non-curative intent treatment groups in the era of modern chemotherapies (i.e., 2010-2018) after propensity score overlap weighting adjustment. (PNG 79 kb)

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Endo, Y., Sasaki, K., Munir, M.M. et al. Survival Benefit Relative to Treatment Modalities Among Patients with Very Early Intrahepatic Cholangiocarcinoma: an Analysis of the National Cancer Database. J Gastrointest Surg 27, 2103–2113 (2023). https://doi.org/10.1007/s11605-023-05821-7

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