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Palliative Chemotherapy and Radiotherapy for Cholangiocarcinoma

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Diagnosis and Management of Cholangiocarcinoma

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Abstract

Patients with cholangiocarcinoma (and other biliary tract cancers) frequently present with advanced disease that is not amenable to surgery and is thus incurable. The aim of treatment for these patients is to prolong life and reduce disease-associated symptoms or complications. Chemotherapy significantly improves overall survival and remains the mainstay of treatment in this regard; however, prognosis remains poor. The frequency of disease confined to the liver provides rationale for loco-regional therapies such as radiotherapy, though the role of radiotherapy is less well-defined than chemotherapy due to a lack of randomized controlled trial evidence. Much-needed trials assessing superior or second-line chemotherapy regimens and novel radiotherapy methods permitting higher dose delivery are underway and likely to add to the currently limited treatment arsenal.

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Abbreviations

BTCs :

biliary tract cancers

CI :

confidence interval

EBRT :

external beam radiotherapy

ECOG :

Eastern Cooperative Oncology Group

EGFR :

Epidermal growth factor receptor

FOLFIRINOX :

5-fluorouracil, leucovorin, oxaliplatin, and irinotecan

5-FU:

fluorouracil

GemCis :

gemcitabine plus cisplatin

Gem-S1 :

gemcitabine plus S1

Gy :

grey

HR :

hazard ratio

ILBT :

Intraluminal brachytherapy

MER :

merestinib

mFOLFOX :

leucovorin, fluorouracil plus oxaliplatin

mGemOx :

modified gemcitabine plus oxaliplatin

OS :

overall survival

P :

p-value

PBT :

proton beam therapy

PFS :

progression-free survival

PS :

performance status

QoL :

quality of life

RAM :

ramucirumab

SBRT :

stereotactic body radiotherapy

SEER :

US Surveillance, Epidemiology, and End Results

SIRT :

selective internal radiotherapy

VEGF :

vascular endothelial growth factor

References

  1. Glimelius B, Hoffman K, Sjoden PO, Jacobsson G, Sellstrom H, Enander LK, et al. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996;7(6):593–600.

    Article  CAS  PubMed  Google Scholar 

  2. Park J, Kim MH, Kim KP, Park DH, Moon SH, Song TJ, et al. Natural history and prognostic factors of advanced Cholangiocarcinoma without surgery, chemotherapy, or radiotherapy: a large-scale observational study. Gut Liver. 2009;3(4):298–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010;28(30):4581–6.

    Article  CAS  PubMed  Google Scholar 

  4. Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer. 2007;96(6):896–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81.

    Article  CAS  PubMed  Google Scholar 

  7. Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103(4):469–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Valle JW, Furuse J, Jitlal M, Beare S, Mizuno N, Wasan H, et al. Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials. Ann Oncol. 2014;25(2):391–8.

    Article  CAS  PubMed  Google Scholar 

  9. Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D, et al. Biliary cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v28–37.

    Article  CAS  PubMed  Google Scholar 

  10. Bridgewater J, Lopes A, Palmer D, Cunningham D, Anthoney A, Maraveyas A, et al. Quality of life, long-term survivors and long-term outcome from the ABC-02 study. Br J Cancer. 2016;114(9):965–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jiao Y, Pawlik TM, Anders RA, Selaru FM, Streppel MM, Lucas DJ, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet. 2013;45(12):1470–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lamarca A, Ross P, Wasan HS, Hubner RA, McNamara MG, Lopes A, et al. Advanced intrahepatic Cholangiocarcinoma: Post Hoc analysis of the ABC-01, -02, and -03 clinical trials. J Natl Cancer Inst. 2020;112(2):200–10.

    PubMed  Google Scholar 

  13. Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, 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):1950–8.

    Article  CAS  PubMed  Google Scholar 

  14. André T, Reyes-Vidal JM, Fartoux L, Ross P, Leslie M, Rosmorduc O, et al. Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study. Br J Cancer. 2008;99(6):862–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Sharma A, Kalyan Mohanti B, Pal Chaudhary S, Sreenivas V, Kumar Sahoo R, Kumar Shukla N, et al. Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: results of a phase III randomised controlled trial. Eur J Cancer. 2019;123:162–70.

    Article  CAS  PubMed  Google Scholar 

  16. Kim Seung, Kang Jung, Lee Jeeyun, Lee Hyun, OH SUNG YONG, Jang Joung, et al. Capecitabine Plus Oxaliplatin Versus Gemcitabine Plus Oxaliplatin as First-Line Therapy for Advanced Biliary Tract Cancers: A Multicenter, Open-Label, Randomized, Phase Three, Non-Inferiority Trial. Annals of oncology: official journal of the European Society for Medical Oncology. 2019;30. 10.1093/annonc/mdz058.

    Google Scholar 

  17. Malka D, Cervera P, Foulon S, Trarbach T, de la Fouchardiere C, Boucher E, et al. Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. Lancet Oncol. 2014;15(8):819–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Valle JW, Wasan H, Lopes A, Backen AC, Palmer DH, Morris K, et al. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial. Lancet Oncol. 2015;16(8):967–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Valle JW, Bai L-Y, Orlova R, Cutsem EV, Alfonso JA, Chen L-T, et al. Ramucirumab (RAM) or merestinib (MER) or placebo (PL) plus gemcitabine (GEM) and cisplatin (CIS) as first-line treatment for advanced or metastatic biliary tract cancer (BTC): a randomized, double-blind, phase II study. J Clin Oncol. 2020;38(4_suppl):477.

    Article  Google Scholar 

  20. Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395–406.

    Article  CAS  PubMed  Google Scholar 

  21. Belkouz A, de Vos-Geelen J, Mathôt RAA, Eskens FALM, van Gulik TM, van Oijen MGH, et al. Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial. Br J Cancer. 2020;122(5):634–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Phelip JM, Edeline J, Blanc JF, Barbier E, Michel P, Bourgeois V, et al. Modified FOLFIRINOX versus CisGem first-line chemotherapy for locally advanced non resectable or metastatic biliary tract cancer (AMEBICA)-PRODIGE 38: study protocol for a randomized controlled multicenter phase II/III study. Dig Liver Dis. 2019;51(2):318–20.

    Article  CAS  PubMed  Google Scholar 

  23. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.

    Article  CAS  Google Scholar 

  24. Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, 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):824–30.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lamarca A, Hubner RA, David Ryder W, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014;25(12):2328–38.

    Article  CAS  PubMed  Google Scholar 

  26. Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, et al. ABC-06 | a randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin / 5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced / metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. J Clin Oncol. 2019;37(15_suppl):4003.

    Article  Google Scholar 

  27. Alden ME, Mohiuddin M. The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer. Int J Radiat Oncol Biol Phys. 1994;28(4):945–51.

    Article  CAS  PubMed  Google Scholar 

  28. Gonzalez Gonzalez D, Gerard JP, Maners AW, De la Lande-Guyaux B, Van Dijk-Milatz A, Meerwaldt JH, et al. Results of radiation therapy in carcinoma of the proximal bile duct (Klatskin tumor). Semin Liver Dis. 1990;10(2):131–41.

    Article  CAS  PubMed  Google Scholar 

  29. Hayes JK, Sapozink MD, Miller FJ. Definitive radiation therapy in bile duct carcinoma. Int J Radiat Oncol Biol Phys. 1988;15(3):735–44.

    Article  PubMed  Google Scholar 

  30. Chen YX, Zeng ZC, Tang ZY, Fan J, Zhou J, Jiang W, et al. Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients. BMC Cancer. 2010;10:492.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Mittal B, Deutsch M, Iwatsuki S. Primary cancers of extrahepatic biliary passages. Int J Radiat Oncol Biol Phys. 1985;11(4):849–54.

    Article  CAS  PubMed  Google Scholar 

  32. Ben-David MA, Griffith KA, Abu-Isa E, Lawrence TS, Knol J, Zalupski M, et al. External-beam radiotherapy for localized extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys. 2006;66(3):772–9.

    Article  PubMed  Google Scholar 

  33. Dawson LA, McGinn CJ, Normolle D, Ten Haken RK, Walker S, Ensminger W, et al. Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies. J Clin Oncol. 2000;18(11):2210–8.

    Article  CAS  PubMed  Google Scholar 

  34. Tao R, Krishnan S, Bhosale PR, Javle MM, Aloia TA, Shroff RT, 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):219–26.

    Article  CAS  PubMed  Google Scholar 

  35. Fields JN, Emami B. Carcinoma of the extrahepatic biliary system--results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys. 1987;13(3):331–8.

    Article  CAS  PubMed  Google Scholar 

  36. Johnson DW, Safai C, Goffinet DR. Malignant obstructive jaundice: treatment with external-beam and intracavitary radiotherapy. Int J Radiat Oncol Biol Phys. 1985;11(2):411–6.

    Article  CAS  PubMed  Google Scholar 

  37. Meyers WC, Jones RS. Internal radiation for bile duct cancer. World J Surg. 1988;12(1):99–104.

    Article  CAS  PubMed  Google Scholar 

  38. Bisello S, Buwenge M, Palloni A, Autorino R, Cellini F, Macchia G, et al. Radiotherapy or chemoradiation in unresectable biliary cancer: a retrospective study. Anticancer Res. 2019;39(6):3095–100.

    Article  CAS  PubMed  Google Scholar 

  39. Brunner TB, Schwab D, Meyer T, Sauer R. Chemoradiation may prolong survival of patients with non-bulky unresectable extrahepatic biliary carcinoma. A retrospective analysis. Strahlenther Onkol. 2004;180(12):751–7.

    Article  PubMed  Google Scholar 

  40. Jonczyk M, Collettini F, Schnapauff D, Geisel D, Boning G, Feldhaus F, et al. Cholangiocarcinoma: CT-guided high-dose rate brachytherapy (CT-HDRBT) for limited (<4 cm) and large (>4 cm) tumors. Anticancer Res. 2018;38(10):5843–52.

    Article  PubMed  Google Scholar 

  41. Yoshioka Y, Ogawa K, Oikawa H, Onishi H, Kanesaka N, Tamamoto T, et al. Impact of intraluminal brachytherapy on survival outcome for radiation therapy for unresectable biliary tract cancer: a propensity-score matched-pair analysis. Int J Radiat Oncol Biol Phys. 2014;89(4):822–9.

    Article  PubMed  Google Scholar 

  42. Crane CH, Macdonald KO, Vauthey JN, Yehuda P, Brown T, Curley S, et al. Limitations of conventional doses of chemoradiation for unresectable biliary cancer. Int J Radiat Oncol Biol Phys. 2002;53(4):969–74.

    Article  PubMed  Google Scholar 

  43. Pollom EL, Alagappan M, Park LS, Whittemore AS, Koong AC, Chang DT. Does radiotherapy still have a role in unresected biliary tract cancer? Cancer Med. 2017;6(1):129–41.

    Article  PubMed  Google Scholar 

  44. Kim YI, Park JW, Kim BH, Woo SM, Kim TH, Koh YH, et al. Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for advanced-stage unresectable intrahepatic cholangiocarcinoma. Radiat Oncol. 2013;8:292.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Phelip JM, Vendrely V, Rostain F, Subtil F, Jouve JL, Gasmi M, et al. Gemcitabine plus cisplatin versus chemoradiotherapy in locally advanced biliary tract cancer: Federation Francophone de Cancerologie Digestive 9902 phase II randomised study. Eur J Cancer. 2014;50(17):2975–82.

    Article  CAS  PubMed  Google Scholar 

  46. Barney BM, Olivier KR, Miller RC, Haddock MG. Clinical outcomes and toxicity using stereotactic body radiotherapy (SBRT) for advanced cholangiocarcinoma. Radiat Oncol. 2012;7:67.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Jung DH, Kim MS, Cho CK, Yoo HJ, Jang WI, Seo YS, et al. Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma. Radiat Oncol J. 2014;32(3):163–9.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kopek N, Holt MI, Hansen AT, Hoyer M. Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol. 2010;94(1):47–52.

    Article  PubMed  Google Scholar 

  49. Mahadevan A, Dagoglu N, Mancias J, Raven K, Khwaja K, Tseng JF, et al. Stereotactic Body Radiotherapy (SBRT) for intrahepatic and Hilar Cholangiocarcinoma. J Cancer. 2015;6(11):1099–104.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Momm F, Schubert E, Henne K, Hodapp N, Frommhold H, Harder J, et al. Stereotactic fractionated radiotherapy for Klatskin tumours. Radiother Oncol. 2010;95(1):99–102.

    Article  PubMed  Google Scholar 

  51. Polistina FA, Guglielmi R, Baiocchi C, Francescon P, Scalchi P, Febbraro A, et al. Chemoradiation treatment with gemcitabine plus stereotactic body radiotherapy for unresectable, non-metastatic, locally advanced hilar cholangiocarcinoma. Results of a five year experience. Radiother Oncol. 2011;99(2):120–3.

    Article  CAS  PubMed  Google Scholar 

  52. Sandler KA, Veruttipong D, Agopian VG, Finn RS, Hong JC, Kaldas FM, et al. Stereotactic body radiotherapy (SBRT) for locally advanced extrahepatic and intrahepatic cholangiocarcinoma. Adv Radiat Oncol. 2016;1(4):237–43.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B, Knox J, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2008;26(4):657–64.

    Article  PubMed  Google Scholar 

  54. Herman JM, Chang DT, Goodman KA, Dholakia AS, Raman SP, Hacker-Prietz A, et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121(7):1128–37.

    Article  CAS  PubMed  Google Scholar 

  55. Aitken KL, Hawkins MA. The role of radiotherapy and chemoradiation in the management of primary liver tumours. Clin Oncol (R Coll Radiol). 2014;26(9):569–80.

    Article  CAS  Google Scholar 

  56. Kang JK, Kim MS, Cho CK, Yang KM, Yoo HJ, Kim JH, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012;118(21):5424–31.

    Article  PubMed  Google Scholar 

  57. Lee JW, Lee SH. Proton beam therapy as a rising option in treating intrahepatic cholangiocarcinoma. Transl Cancer Res. 2017;6(1):S96–S8.

    Google Scholar 

  58. Hong TS, Wo JY, Yeap BY, Ben-Josef E, McDonnell EI, Blaszkowsky LS, 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):460–8.

    Article  CAS  PubMed  Google Scholar 

  59. Ohkawa A, Mizumoto M, Ishikawa H, Abei M, Fukuda K, Hashimoto T, et al. Proton beam therapy for unresectable intrahepatic cholangiocarcinoma. J Gastroenterol Hepatol. 2015;30(5):957–63.

    Article  PubMed  Google Scholar 

  60. Makita C, Nakamura T, Takada A, Takayama K, Suzuki M, Ishikawa Y, et al. Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma. Radiat Oncol. 2014;9(1):26.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, University College London Hospital, London, UK

    Sonya Hessey

  2. Department of Medical Oncology, University College London Cancer Institute, London, UK

    John Bridgewater

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Correspondence to Sonya Hessey .

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  1. Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA

    James H. Tabibian

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Hessey, S., Bridgewater, J. (2021). Palliative Chemotherapy and Radiotherapy for Cholangiocarcinoma. In: Tabibian, J.H. (eds) Diagnosis and Management of Cholangiocarcinoma. Springer, Cham. https://doi.org/10.1007/978-3-030-70936-5_17

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