Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians

Dimitrios Moris, Manisha Palta, Charles Kim, Peter J Allen, Michael A Morse, Michael E Lidsky, Dimitrios Moris, Manisha Palta, Charles Kim, Peter J Allen, Michael A Morse, Michael E Lidsky

Abstract

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.

Keywords: chemotherapy; immunotherapy; intrahepatic cholangiocarcinoma; locoregional therapies.

© 2022 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.

References

REFERENCES

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA A Cancer J Clin. 2022;72(1):7-33. doi:10.3322/caac.21708
    1. Beal EW, Tumin D, Moris D, et al. Cohort contributions to trends in the incidence and mortality of intrahepatic cholangiocarcinoma. Hepatobiliary Surg Nutr. 2018;7(4):270-276. doi:10.21037/hbsn.2018.03.16
    1. Saha SK, Zhu AX, Fuchs CS, Brooks GA. Forty-year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise. Oncologist. 2016;21(5):594-599. doi:10.1634/theoncologist.2015-0446
    1. Labib PL, Goodchild G, Pereira SP. Molecular pathogenesis of cholangiocarcinoma. BMC Cancer. 2019;19(1):185. doi:10.1186/s12885-019-5391-0
    1. Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: epidemiology and risk factors. Liver Int. 2019;39(suppl 1):19-31. doi:10.1111/liv.14095
    1. Welzel TM, Graubard BI, El-Serag HB, et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case-control study. Clin Gastroenterol Hepatol. 2007;5(10):1221-1228. doi:10.1016/j.cgh.2007.05.020
    1. Welzel TM, Mellemkjaer L, Gloria G, et al. Risk factors for intrahepatic cholangiocarcinoma in a low-risk population: a nationwide case-control study. Int J Cancer. 2007;120(3):638-641. doi:10.1002/ijc.22283
    1. Chapman RW. Risk factors for biliary tract carcinogenesis. Ann Oncol. 1999;10(suppl 4):308-311. doi:10.1093/annonc/10.suppl_4.s308
    1. Chang KY, Chang JY, Yen Y. Increasing incidence of intrahepatic cholangiocarcinoma and its relationship to chronic viral hepatitis. J Natl Compr Canc Netw. 2009;7(4):423-427. doi:10.6004/jnccn.2009.0030
    1. Tyson GL, El-Serag HB. Risk factors for cholangiocarcinoma. Hepatology. 2011;54(1):173-184. doi:10.1002/hep.24351
    1. Brown KM, Parmar AD, Geller DA. Intrahepatic cholangiocarcinoma. Surg Oncol Clin N Am. 2014;23(2):231-246. doi:10.1016/j.soc.2013.10.004
    1. Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma-evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15(2):95-111. doi:10.1038/nrclinonc.2017.157
    1. Bertuccio P, Malvezzi M, Carioli G, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019;71(1):104-114. doi:10.1016/j.jhep.2019.03.013
    1. Yao KJ, Jabbour S, Parekh N, Lin Y, Moss RA. Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database. BMC Gastroenterol. 2016;16(1):117. doi:10.1186/s12876-016-0527-z
    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(1):84-96. doi:10.1097/sla.0b013e318176c4d3
    1. El-Diwany R, Pawlik TM, Ejaz A. Intrahepatic cholangiocarcinoma. Surg Oncol Clin N Am. 2019;28(4):587-599. doi:10.1016/j.soc.2019.06.002
    1. Primrose JN, Fox RP, Palmer DH, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20(5):663-673. doi:10.1016/s1470-2045(18)30915-x
    1. Dhanasekaran R, Hemming AW, Zendejas I, et al. Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma. Oncol Rep. 2013;29(4):1259-1267. doi:10.3892/or.2013.2290
    1. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-1281. doi:10.1056/nejmoa0908721
    1. Benson AB 3rd, D'Angelica MI, Abrams TA, et al. Hepatobiliary cancers, version 2.2014. J Natl Compr Canc Netw. 2014;12(8):1152-1182. doi:10.6004/jnccn.2014.0112
    1. Woods E, Le D, Jakka BK, Manne A. Changing landscape of systemic therapy in biliary tract cancer. Cancers (Basel). 2022;14(9):2137. doi:10.3390/cancers14092137
    1. Sia D, Tovar V, Moeini A, Llovet JM. Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies. Oncogene. 2013;32(41):4861-4870. doi:10.1038/onc.2012.617
    1. Moeini A, Sia D, Bardeesy N, Mazzaferro V, Llovet JM. Molecular pathogenesis and targeted therapies for intrahepatic cholangiocarcinoma. Clin Cancer Res. 2016;22(2):291-300. doi:10.1158/1078-0432.ccr-14-3296
    1. Saha SK, Gordan JD, Kleinstiver BP, et al. Isocitrate dehydrogenase mutations confer dasatinib hypersensitivity and SRC dependence in intrahepatic cholangiocarcinoma. Cancer Discov. 2016;6(7):727-739. doi:10.1158/-15-1442
    1. Pellino A, Loupakis F, Cadamuro M, et al. Precision medicine in cholangiocarcinoma. Transl Gastroenterol Hepatol. 2018;3:40. doi:10.21037/tgh.2018.07.02
    1. Wang N, Huang A, Kuang B, Xiao Y, Xiao Y, Ma H. Progress in radiotherapy for cholangiocarcinoma. Front Oncol. 2022;12:868034. doi:10.3389/fonc.2022.868034
    1. Holster JJ, El Hassnaoui M, Franssen S, et al. Hepatic arterial infusion pump chemotherapy for unresectable intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. Ann Surg Oncol. 2022;29(9):5528-5538. doi:10.1245/s10434-022-11439-x
    1. Blechacz B, Komuta M, Roskams T, Gores GJ. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2011;8:512-522.
    1. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 2013;145(6):1215-1229. doi:10.1053/j.gastro.2013.10.013
    1. Altekruse SF, Petrick JL, Rolin AI, et al. Geographic variation of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and hepatocellular carcinoma in the United States. PLoS One. 2015;10(4):e0120574. doi:10.1371/journal.pone.0120574
    1. Florio AA, Ferlay J, Znaor A, et al. Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012. Cancer. 2020;126(11):2666-2678. doi:10.1002/cncr.32803
    1. Gad MM, Saad AM, Faisaluddin M, et al. Epidemiology of cholangiocarcinoma; United States incidence and mortality trends. Clin Res Hepatol Gastroenterol. 2020;44(6):885-893. doi:10.1016/j.clinre.2020.03.024
    1. Patel T. Worldwide trends in mortality from biliary tract malignancies. BMC Cancer. 2002;2(1):10. doi:10.1186/1471-2407-2-10
    1. Ouyang G, Liu Q, Wu Y, et al. The global, regional, and national burden of gallbladder and biliary tract cancer and its attributable risk factors in 195 countries and territories, 1990 to 2017: a systematic analysis for the Global Burden of Disease Study 2017. Cancer. 2021;127(13):2238-2250. doi:10.1002/cncr.33476
    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(6):1471-1474. doi:10.1245/s10434-010-0985-4
    1. Farges O, Fuks D, Le Treut YP, 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(10):2170-2177. doi:10.1002/cncr.25712
    1. Doussot A, Gonen M, Wiggers JK, et al. Recurrence patterns and disease-free survival after resection of intrahepatic cholangiocarcinoma: preoperative and postoperative prognostic models. J Am Coll Surg. 2016;223(3):493-505.e2. doi:10.1016/j.jamcollsurg.2016.05.019
    1. Kim Y, Moris DP, Zhang XF, et al. Evaluation of the 8th edition American Joint Commission on Cancer (AJCC) staging system for patients with intrahepatic cholangiocarcinoma: a Surveillance, Epidemiology, and End Results (SEER) analysis. J Surg Oncol. 2017;116(6):643-650. doi:10.1002/jso.24720
    1. Spolverato G, Bagante F, Weiss M, et al. Comparative performances of the 7th and the 8th editions of the American Joint Committee on Cancer staging systems for intrahepatic cholangiocarcinoma. J Surg Oncol. 2017;115(6):696-703. doi:10.1002/jso.24569
    1. Kang SH, Hwang S, Lee YJ, et al. Prognostic comparison of the 7th and 8th editions of the American Joint Committee on Cancer staging system for intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2018;25(4):240-248. doi:10.1002/jhbp.543
    1. Forner A, Vidili G, Rengo M, Bujanda L, Ponz-Sarvise M, Lamarca A. Clinical presentation, diagnosis and staging of cholangiocarcinoma. Liver Int. 2019;39(suppl 1):98-107. doi:10.1111/liv.14086
    1. Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg. 1996;224(4):463-473. discussion 473-465. doi:10.1097/00000658-199610000-00005
    1. Tao LY, Cai L, He XD, Liu W, Qu Q. Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Am Surg. 2010;76(11):1210-1213. doi:10.1177/000313481007601119
    1. Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ. The utility of CA 19.9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol. 2000;95(1):204-207. doi:10.1111/j.1572-0241.2000.01685.x
    1. Izquierdo-Sanchez L, Lamarca A, La Casta A, et al. Cholangiocarcinoma landscape in Europe: diagnostic, prognostic and therapeutic insights from the ENSCCA Registry. J Hepatol. 2022;76(5):1109-1121. doi:10.1016/j.jhep.2021.12.010
    1. Nehls O, Gregor M, Klump B. Serum and bile markers for cholangiocarcinoma. Semin Liver Dis. 2004;24(02):139-154. doi:10.1055/s-2004-828891
    1. Tsilimigras DI, Hyer JM, Moris D, et al. Prognostic utility of albumin-bilirubin grade for short- and long-term outcomes following hepatic resection for intrahepatic cholangiocarcinoma: a multi-institutional analysis of 706 patients. J Surg Oncol. 2019;120:206-213. doi:10.1002/jso.25486
    1. Lu LH, Zhong C, Wei W, et al. Lymphocyte-C-reactive protein ratio as a novel prognostic index in intrahepatic cholangiocarcinoma: a multicentre cohort study. Liver Int. 2021;41(2):378-387. doi:10.1111/liv.14567
    1. Tsilimigras DI, Mehta R, Aldrighetti L, et al. Development and validation of a laboratory risk score (LabScore) to predict outcomes after resection for intrahepatic cholangiocarcinoma. J Am Coll Surg. 2020;230(4):381-391.e2. doi:10.1016/j.jamcollsurg.2019.12.025
    1. Kovac JD, Jankovic A, Dikic-Rom A, Grubor N, Antic A, Dugalic V. Imaging spectrum of intrahepatic mass-forming cholangiocarcinoma and its mimickers: how to differentiate them using MRI. Curr Oncol. 2022;29(2):698-723. doi:10.3390/curroncol29020061
    1. Vilgrain V. Staging cholangiocarcinoma by imaging studies. HPB (Oxford). 2008;10(2):106-109. doi:10.1080/13651820801992617
    1. Han JK, Choi BI, Kim AY, et al. Cholangiocarcinoma: pictorial essay of CT and cholangiographic findings. Radiographics. 2002;22(1):173-187. doi:10.1148/radiographics.22.1.g02ja15173
    1. Iavarone M, Piscaglia F, Vavassori S, et al. Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis. J Hepatol. 2013;58(6):1188-1193. doi:10.1016/j.jhep.2013.02.013
    1. Kim SH, Lee CH, Kim BH, et al. Typical and atypical imaging findings of intrahepatic cholangiocarcinoma using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging. J Comput Assist Tomogr. 2012;36(6):704-709. doi:10.1097/rct.0b013e3182706562
    1. Manfredi R, Barbaro B, Masselli G, Vecchioli A, Marano P. Magnetic resonance imaging of cholangiocarcinoma. Semin Liver Dis. 2004;24(02):155-164. doi:10.1055/s-2004-828892
    1. National Comprehensive Cancer Network®(NCCN). NCCN Clinical Practice Guidelines in Oncology. Accessed May 31, 2022.
    1. Hiley C, de Bruin EC, McGranahan N, Swanton C. Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine. Genome Biol. 2014;15(8):453. doi:10.1186/s13059-014-0453-8
    1. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883-892. doi:10.1056/nejmoa1113205
    1. Brandi G, Farioli A, Astolfi A, Biasco G, Tavolari S. Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies. Oncotarget. 2015;6(17):14744-14753. doi:10.18632/oncotarget.4539
    1. Larribere L, Martens UM. Advantages and challenges of using ctDNA NGS to assess the presence of minimal residual disease (MRD) in solid tumors. Cancers (Basel). 2021;13(22):5698. doi:10.3390/cancers13225698
    1. Mody K, Kasi PM, Yang J, et al. Circulating tumor DNA profiling of advanced biliary tract cancers. JCO Precis Oncol. 2019;3:1-9. doi:10.1200/po.18.00324
    1. Chen C, Wang T, Yang M, et al. Genomic profiling of blood-derived circulating tumor DNA from patients with advanced biliary tract cancer. Pathol Oncol Res. 2021;27:1609879. doi:10.3389/pore.2021.1609879
    1. Zou S, Li J, Zhou H, et al. Mutational landscape of intrahepatic cholangiocarcinoma. Nat Commun. 2014;5(1):5696. doi:10.1038/ncomms6696
    1. Csoma SL, Bedekovics J, Veres G, et al. Circulating cell-free DNA-based comprehensive molecular analysis of biliary tract cancers using next-generation sequencing. Cancers (Basel). 2022;14(1):233. doi:10.3390/cancers14010233
    1. Jusakul A, Cutcutache I, Yong CH, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov. 2017;7(10):1116-1135. doi:10.1158/-17-0368
    1. Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res. 2018;24(17):4154-4161. doi:10.1158/1078-0432.ccr-18-0078
    1. Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: systematic review and meta-analysis. JAMA Surg. 2014;149(6):565-574. doi:10.1001/jamasurg.2013.5137
    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(12):1107-1113. doi:10.1001/archsurg.2012.1962
    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(5):824-829. discussion 830. doi:10.1097/sla.0b013e318236c21d
    1. Spolverato G, Yakoob MY, Kim Y, et al. The impact of surgical margin status on long-term outcome after resection for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2015;22(12):4020-4028. doi:10.1245/s10434-015-4472-9
    1. Zhang XF, Bagante F, Chakedis J, et al. Perioperative and long-term outcome for intrahepatic cholangiocarcinoma: impact of major versus minor hepatectomy. J Gastrointest Surg. 2017;21(11):1841-1850. doi:10.1007/s11605-017-3499-6
    1. Sahara K, Tsilimigras DI, Merath K, et al. Therapeutic index associated with lymphadenectomy among patients with intrahepatic cholangiocarcinoma: which patients benefit the most from nodal evaluation? Ann Surg Oncol. 2019;26(9):2959-2968. doi:10.1245/s10434-019-07483-9
    1. Zhou R, Lu D, Li W, et al. Is lymph node dissection necessary for resectable intrahepatic cholangiocarcinoma? A systematic review and meta-analysis. HPB (Oxford). 2019;21(7):784-792. doi:10.1016/j.hpb.2018.12.011
    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(23):3140-3145. doi:10.1200/jco.2011.35.6519
    1. Zhang XF, Xue F, Dong DH, et al. Number and station of lymph node metastasis after curative-intent resection of intrahepatic cholangiocarcinoma impact prognosis. Ann Surg. 2021;274(6):e1187-e1195. doi:10.1097/sla.0000000000003788
    1. Tsilimigras DI, Hyer JM, Paredes AZ, et al. The optimal number of lymph nodes to evaluate among patients undergoing surgery for gallbladder cancer: correlating the number of nodes removed with survival in 6531 patients. J Surg Oncol. 2019;119(8):1099-1107. doi:10.1002/jso.25450
    1. Kim SH, Han DH, Choi GH, Choi JS, Kim KS. Extent of lymph node dissection for accurate staging in intrahepatic cholangiocarcinoma. J Gastrointest Surg. 2022;26(1):70-76. doi:10.1007/s11605-021-05039-5
    1. Zhang XF, Chakedis J, Bagante F, et al. Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma. Br J Surg. 2018;105(7):857-866. doi:10.1002/bjs.10827
    1. Luvira V, Eurboonyanun C, Bhudhisawasdi V, et al. Patterns of recurrence after resection of mass-forming type intrahepatic cholangiocarcinomas. Asian Pac J Cancer Prev. 2016;17:4735-4739.
    1. Tsilimigras DI, Sahara K, Wu L, et al. Very early recurrence after liver resection for intrahepatic cholangiocarcinoma: considering alternative treatment approaches. JAMA Surg. 2020;155(9):823-831. doi:10.1001/jamasurg.2020.1973
    1. Wang Y, Li J, Xia Y, et al. Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy. J Clin Oncol. 2013;31(9):1188-1195. doi:10.1200/jco.2012.41.5984
    1. Tsilimigras DI, Hyer JM, Paredes AZ, et al. Tumor burden dictates prognosis among patients undergoing resection of intrahepatic cholangiocarcinoma: a tool to guide post-resection adjuvant chemotherapy? Ann Surg Oncol. 2021;28(4):1970-1978. doi:10.1245/s10434-020-09393-7
    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(5):432-438. doi:10.1001/jamasurg.2013.5168
    1. Zhou SL, Xin HY, Sun RQ, et al. Association of KRAS variant subtypes with survival and recurrence in patients with surgically treated intrahepatic cholangiocarcinoma. JAMA Surg. 2022;157(1):59-65. doi:10.1001/jamasurg.2021.5679
    1. Edeline J, Benabdelghani M, Bertaut A, et al. Gemcitabine and oxaliplatin chemotherapy or surveillance in resected biliary tract cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): a randomized phase III study. J Clin Oncol. 2019;37(8):658-667. doi:10.1200/jco.18.00050
    1. Bridgewater J, Fletcher P, Palmer DH, et al. Long-term outcomes and exploratory analyses of the randomized phase III BILCAP study. J Clin Oncol. 2022;40(18):2048-2057. doi:10.1200/jco.21.02568
    1. Siebenhuner AR, Seifert H, Bachmann H, et al. Adjuvant treatment of resectable biliary tract cancer with cisplatin plus gemcitabine: a prospective single center phase II study. BMC Cancer. 2018;18(1):72. doi:10.1186/s12885-017-3967-0
    1. Stein A, Arnold D, Bridgewater J, et al. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial)-a randomized, multidisciplinary, multinational phase III trial. BMC Cancer. 2015;15(1):564. doi:10.1186/s12885-015-1498-0
    1. Nakachi K, Konishi M, Ikeda M, et al. A randomized phase III trial of adjuvant S-1 therapy vs. observation alone in resected biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1202, ASCOT). Jpn J Clin Oncol. 2018;48(4):392-395. doi:10.1093/jjco/hyy004
    1. Shanghai Zhongshan Hospital. Oxaliplatin+Gemcitabine vs Capecitabine as Adjuvant Therapy for Intrahepatic Cholangiocarcinoma. identifier NCT02548195. Accessed May 31, 2022.
    1. Shanghai Zhongshan Hospital. Nab-Paclitaxel Combined With Gemcitabine Adjuvant Chemotherapy After Radical Resection of Intrahepatic Cholangiocarcinoma. identifier NCT04077983. Accessed May 31, 2022.
    1. Medin CR, Maithel SK. Neoadjuvant therapy trials in biliary tract malignancies. J Surg Oncol. 2022;125(1):84-88. doi:10.1002/jso.26714
    1. Rizzo A, Brandi G. Neoadjuvant therapy for cholangiocarcinoma: a comprehensive literature review. Cancer Treat Res Commun. 2021;27:100354. doi:10.1016/j.ctarc.2021.100354
    1. Yadav S, Xie H, Bin-Riaz I, et al. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: a propensity score matched analysis. Eur J Surg Oncol. 2019;45(8):1432-1438. doi:10.1016/j.ejso.2019.03.023
    1. Mason MC, Massarweh NN, Tzeng CD, et al. Time to rethink upfront surgery for resectable intrahepatic cholangiocarcinoma? Implications from the neoadjuvant experience. Ann Surg Oncol. 2021;28(11):6725-6735. doi:10.1245/s10434-020-09536-w
    1. Maithel SK, Javle MM, Mahipal A, et al. NEO-GAP: a phase II single-arm prospective feasibility study of neoadjuvant gemcitabine/cisplatin/nab-paclitaxel for resectable high-risk intrahepatic cholangiocarcinoma. J Clin Oncol. 2022;40(16 suppl):4097. doi:10.1200/jco.2022.40.16_suppl.4097
    1. Khon Kaen University. Neoadjuvant mFOLFOXIRI for Potentially Resectable Cholangiocarcinoma. identifier NCT03603834. Accessed May 31, 2022.
    1. Goetze TO, Bechstein WO, Bankstahl US, et al. Neoadjuvant chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus immediate radical liver resection alone with or without adjuvant chemotherapy in incidentally detected gallbladder carcinoma after simple cholecystectomy or in front of radical resection of BTC (ICC/ECC)-a phase III study of the German registry of incidental gallbladder carcinoma platform (GR)-the AIO/CALGP/ACO- GAIN-trial. BMC Cancer. 2020;20(1):122. doi:10.1186/s12885-020-6610-4
    1. Kiefer MV, Albert M, McNally M, et al. Chemoembolization of intrahepatic cholangiocarcinoma with cisplatinum, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol: a 2-center study. Cancer. 2011;117(7):1498-1505. doi:10.1002/cncr.25625
    1. Kim JH, Yoon HK, Sung KB, et al. Transcatheter arterial chemoembolization or chemoinfusion for unresectable intrahepatic cholangiocarcinoma: clinical efficacy and factors influencing outcomes. Cancer. 2008;113(7):1614-1622. doi:10.1002/cncr.23787
    1. Vogl TJ, Naguib NN, Nour-Eldin NE, et al. Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: results and prognostic factors governing treatment success. Int J Cancer. 2012;131(3):733-740. doi:10.1002/ijc.26407
    1. Park SY, Kim JH, Yoon HJ, Lee IS, Yoon HK, Kim KP. Transarterial chemoembolization versus supportive therapy in the palliative treatment of unresectable intrahepatic cholangiocarcinoma. Clin Radiol. 2011;66(4):322-328. doi:10.1016/j.crad.2010.11.002
    1. Martin RCG 2nd, Simo KA, Hansen P, et al. Drug-eluting bead, irinotecan therapy of unresectable intrahepatic cholangiocarcinoma (DELTIC) with concomitant systemic gemcitabine and cisplatin. Ann Surg Oncol. 2022;29(9):5462-5473. doi:10.1245/s10434-022-11932-3
    1. Ibrahim SM, Mulcahy MF, Lewandowski RJ, et al. Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer. 2008;113(8):2119-2128. doi:10.1002/cncr.23818
    1. Mouli S, Memon K, Baker T, et al. Yttrium-90 radioembolization for intrahepatic cholangiocarcinoma: safety, response, and survival analysis. J Vasc Interv Radiol. 2013;24(8):1227-1234. doi:10.1016/j.jvir.2013.02.031
    1. Mosconi C, Gramenzi A, Ascanio S, et al. Yttrium-90 radioembolization for unresectable/recurrent intrahepatic cholangiocarcinoma: a survival, efficacy and safety study. Br J Cancer. 2016;115(3):297-302. doi:10.1038/bjc.2016.191
    1. Gangi A, Shah J, Hatfield N, et al. Intrahepatic cholangiocarcinoma treated with transarterial yttrium-90 glass microsphere radioembolization: results of a single institution retrospective study. J Vasc Interv Radiol. 2018;29(8):1101-1108. doi:10.1016/j.jvir.2018.04.001
    1. Edeline J, Touchefeu Y, Guiu B, et al. Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2020;6(1):51-59. doi:10.1001/jamaoncol.2019.3702
    1. Buettner S, Braat A, Margonis GA, et al. Yttrium-90 radioembolization in intrahepatic cholangiocarcinoma: a multicenter retrospective analysis. J Vasc Interv Radiol. 2020;31(7):1035-1043.e2. doi:10.1016/j.jvir.2020.02.008
    1. Cucchetti A, Cappelli A, Mosconi C, et al. Improving patient selection for selective internal radiation therapy of intra-hepatic cholangiocarcinoma: a meta-regression study. Liver Int. 2017;37(7):1056-1064. doi:10.1111/liv.13382
    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(9):3102-3108. doi:10.1245/s10434-014-4365-3
    1. Hoffmann RT, Paprottka PM, Schon A, et al. Transarterial hepatic yttrium-90 radioembolization in patients with unresectable intrahepatic cholangiocarcinoma: factors associated with prolonged survival. Cardiovasc Interv Radiol. 2012;35(1):105-116. doi:10.1007/s00270-011-0142-x
    1. Paprottka KJ, Galie F, Ingrisch M, et al. Outcome and safety after 103 radioembolizations with yttrium-90 resin microspheres in 73 patients with unresectable intrahepatic cholangiocarcinoma-an evaluation of predictors. Cancers (Basel). 2021;13(21):5399. doi:10.3390/cancers13215399
    1. Gabr A, Riaz A, Johnson GE, et al. Correlation of Y90-absorbed radiation dose to pathological necrosis in hepatocellular carcinoma: confirmatory multicenter analysis in 45 explants. Eur J Nucl Med Mol Imaging. 2021;48(2):580-583. doi:10.1007/s00259-020-04976-8
    1. Kurilova I, Bendet A, Fung EK, et al. Radiation segmentectomy of hepatic metastases with Y-90 glass microspheres. Abdom Radiol (NY). 2021;46(7):3428-3436. doi:10.1007/s00261-021-02956-6
    1. Montazeri SA, De la Garza-Ramos C, Lewis AR, et al. Hepatocellular carcinoma radiation segmentectomy treatment intensification prior to liver transplantation increases rates of complete pathologic necrosis: an explant analysis of 75 tumors. Eur J Nucl Med Mol Imaging. 2022;49(11):3892-3897. doi:10.1007/s00259-022-05776-y
    1. Medical University of South Carolina. 90Y Transarterial Radioembolization (TARE) Plus Gemcitabine and Cisplatin in Unresectable Intrahepatic Cholangiocarcinoma. identifier NCT02512692. Accessed May 31, 2022.
    1. Sigurdson ER, Ridge JA, Kemeny N, Daly JM. Tumor and liver drug uptake following hepatic artery and portal vein infusion. J Clin Oncol. 1987;5(11):1836-1840. doi:10.1200/jco.1987.5.11.1836
    1. Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol. 1954;30:969-977.
    1. Ensminger WD, Gyves JW. Clinical pharmacology of hepatic arterial chemotherapy. Semin Oncol. 1983;10:176-182.
    1. Creasy JM, Napier KJ, Reed SA, et al. Implementation of a hepatic artery infusion program: initial patient selection and perioperative outcomes of concurrent hepatic artery infusion and systemic chemotherapy for colorectal liver metastases. Ann Surg Oncol. 2020;27(13):5086-5095. doi:10.1245/s10434-020-08972-y
    1. Datta J, Narayan RR, Kemeny NE, D'Angelica MI. Role of hepatic artery infusion chemotherapy in treatment of initially unresectable colorectal liver metastases: a review. JAMA Surg. 2019;154(8):768-776. doi:10.1001/jamasurg.2019.1694
    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(9):1589-1595. doi:10.1093/annonc/mdp029
    1. Kemeny NE, Schwartz L, Gonen M, et al. Treating primary liver cancer with hepatic arterial infusion of floxuridine and dexamethasone: does the addition of systemic bevacizumab improve results? Oncology. 2011;80(3-4):153-159. doi:10.1159/000324704
    1. Konstantinidis IT, Groot Koerkamp B, Do RK, et al. Unresectable intrahepatic cholangiocarcinoma: systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone. Cancer. 2016;122(5):758-765. doi:10.1002/cncr.29824
    1. Wright GP, Perkins S, Jones H, et al. Surgical resection does not improve survival in multifocal intrahepatic cholangiocarcinoma: a comparison of surgical resection with intra-arterial therapies. Ann Surg Oncol. 2018;25(1):83-90. doi:10.1245/s10434-017-6110-1
    1. Cercek A, Boerner T, Tan BR, et al. Assessment of hepatic arterial infusion of floxuridine in combination with systemic gemcitabine and oxaliplatin in patients with unresectable intrahepatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2020;6(1):60-67. doi:10.1001/jamaoncol.2019.3718
    1. Pietge H, Sanchez-Velazquez P, Akhoundova D, et al. Combination of HAI-FUDR and systemic gemcitabine and cisplatin in unresectable cholangiocarcinoma: a dose finding single center study. Oncology. 2021;99(5):300-309. doi:10.1159/000512967
    1. Jolissaint JS, Soares KC, Seier KP, et al. Intrahepatic cholangiocarcinoma with lymph node metastasis: treatment-related outcomes and the role of tumor genomics in patient selection. Clin Cancer Res. 2021;27(14):4101-4108. doi:10.1158/1078-0432.ccr-21-0412
    1. Franssen S, Soares KC, Jolissaint JS, et al. Comparison of hepatic arterial infusion pump chemotherapy vs resection for patients with multifocal intrahepatic cholangiocarcinoma. JAMA Surg. 2022;157(7):590. doi:10.1001/jamasurg.2022.1298
    1. Kim GH, Kim PH, Kim JH, Won HJ, Shin YM, Choi SH. Thermal ablation in the treatment of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. Eur Radiol. 2022;32(2):1205-1215. doi:10.1007/s00330-021-08216-x
    1. Zhang SJ, Hu P, Wang N, et al. Thermal ablation versus repeated hepatic resection for recurrent intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2013;20(11):3596-3602. doi:10.1245/s10434-013-3035-1
    1. Han K, Ko HK, Kim KW, Won HJ, Shin YM, Kim PN. Radiofrequency ablation in the treatment of unresectable intrahepatic cholangiocarcinoma: systematic review and meta-analysis. J Vasc Interv Radiol. 2015;26(7):943-948. doi:10.1016/j.jvir.2015.02.024
    1. Mosconi C, Calandri M, Javle M, Odisio BC. Interventional radiology approaches for intra-hepatic cholangiocarcinoma. Chin Clin Oncol. 2020;9(1):8. doi:10.21037/cco.2019.12.15
    1. Kirkpatrick JP, Kelsey CR, Palta M, et al. Stereotactic body radiotherapy: a critical review for nonradiation oncologists. Cancer. 2014;120(7):942-954. doi:10.1002/cncr.28515
    1. Tao R, Krishnan S, Bhosale PR, et al. Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol. 2016;34(3):219-226. doi:10.1200/jco.2015.61.3778
    1. Hong TS, Wo JY, Ben-Josef E, et al. Yeap BY, et al. Multi-institutional phase II study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2016;34(5):460-468. doi:10.1200/jco.2015.64.2710
    1. Goldaracena N, Gorgen A, Sapisochin G. Current status of liver transplantation for cholangiocarcinoma. Liver Transpl. 2018;24(2):294-303. doi:10.1002/lt.24955
    1. Moris D, Tsilimigras DI, Ntanasis-Stathopoulos I, et al. Liver transplantation in patients with liver metastases from neuroendocrine tumors: a systematic review. Surgery. 2017;162(3):525-536. doi:10.1016/j.surg.2017.05.006
    1. Moris D, Tsilimigras DI, Chakedis J, et al. Liver transplantation for unresectable colorectal liver metastases: a systematic review. J Surg Oncol. 2017;116(3):288-297. doi:10.1002/jso.24671
    1. Moris D, Kostakis ID, Machairas N, et al. Comparison between liver transplantation and resection for hilar cholangiocarcinoma: a systematic review and meta-analysis. PLoS One. 2019;14(7):e0220527. doi:10.1371/journal.pone.0220527
    1. 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):117-122. doi:10.1007/s11605-007-0335-4
    1. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693-699. doi:10.1056/nejm199603143341104
    1. Sapisochin G, de Lope CR, Gastaca M, et al. Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study. Ann Surg. 2014;259(5):944-952. doi:10.1097/sla.0000000000000494
    1. Sapisochin G, Ivanics T, Heimbach J. Liver transplantation for intrahepatic cholangiocarcinoma: ready for prime time? Hepatology. 2022;75(2):455-472. doi:10.1002/hep.32258
    1. Lunsford KE, Javle M, Heyne K, et al. Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. Lancet Gastroenterol Hepatol. 2018;3(5):337-348. doi:10.1016/s2468-1253(18)30045-1
    1. Sapisochin G, Facciuto M, Rubbia-Brandt L, et al. Liver transplantation for “very early” intrahepatic cholangiocarcinoma: international retrospective study supporting a prospective assessment. Hepatology. 2016;64(4):1178-1188. doi:10.1002/hep.28744
    1. McMillan RR, et al. Survival following liver transplantation for locally advanced, unresectable intrahepatic cholangiocarcinoma. Am J Transplant. 2022;22(3):823-832.
    1. Morizane C, Okusaka T, Mizusawa J, et al. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019;30(12):1950-1958. doi:10.1093/annonc/mdz402
    1. Phelip JM, Desrame J, Edeline J, et al. Modified FOLFIRINOX versus CISGEM chemotherapy for patients with advanced biliary tract cancer (PRODIGE 38 AMEBICA): a randomized phase II study. J Clin Oncol. 2022;40(3):262-271. doi:10.1200/jco.21.00679
    1. Shroff RT, Javle MM, Xiao L, et al. Gemcitabine, cisplatin, and nab-paclitaxel for the treatment of advanced biliary tract cancers: a phase 2 clinical trial. JAMA Oncol. 2019;5(6):824-830. doi:10.1001/jamaoncol.2019.0270
    1. Aitcheson G, Mahipal A, John BV. Targeting FGFR in intrahepatic cholangiocarcinoma [iCCA]: leading the way for precision medicine in biliary tract cancer [BTC]? Expert Opin Investig Drugs. 2021;30(4):463-477. doi:10.1080/13543784.2021.1900821
    1. Rizzo A, Ricci AD, Brandi G. IDH inhibitors in advanced cholangiocarcinoma: another arrow in the quiver? Cancer Treat Res Commun. 2021;27:100356. doi:10.1016/j.ctarc.2021.100356
    1. Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21(5):671-684. doi:10.1016/s1470-2045(20)30109-1
    1. Javle M, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36(3):276-282. doi:10.1200/jco.2017.75.5009
    1. Lowery MA, Burris HA 3rd, Janku F, et al. Safety and activity of ivosidenib in patients with IDH1-mutant advanced cholangiocarcinoma: a phase 1 study. Lancet Gastroenterol Hepatol. 2019;4(9):711-720. doi:10.1016/s2468-1253(19)30189-x
    1. Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(6):796-807. doi:10.1016/s1470-2045(20)30157-1
    1. Zhu AX, Macarulla T, Javle MM, et al. Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: the phase 3 randomized clinical ClarIDHy trial. JAMA Oncol. 2021;7(11):1669-1677. doi:10.1001/jamaoncol.2021.3836
    1. Fiste O, Ntanasis-Stathopoulos I, Gavriatopoulou M, et al. The emerging role of immunotherapy in intrahepatic cholangiocarcinoma. Vaccines (Basel). 2021;9(5):422. doi:10.3390/vaccines9050422
    1. Oh D-Y, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J Clin Oncol. 2022;40(4 suppl):378. doi:10.1200/jco.2022.40.4_suppl.378
    1. Vogel A, Chen L-T, He AR, et al. Regional subgroup analysis of the phase 3 TOPAZ-1 study of durvalumab (D) plus gemcitabine and cisplatin (GC) in advanced biliary tract cancer (BTC). J Clin Oncol. 2022;40(16 suppl):4075. doi:10.1200/jco.2022.40.16_suppl.4075

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi