Advertisement

Strahlentherapie und Onkologie

, Volume 186, Issue 12, pp 672–680 | Cite as

Radiotherapy and Chemotherapy as Therapeutic Strategies in Extrahepatic Biliary Duct Carcinoma

  • Thomas B. Brunner
  • Cynthia L. Eccles
Original Article

Abstract

Purpose:

This report aims to provide an overview on radiotherapy and chemotherapy in extrahepatic biliary duct carcinoma (BDC).

Patients and Methods:

A PubMed research identified clinical trials in BDC through April 1, 2010 including randomised controlled trials, SEER analyses and retrospective trials. Additionally, publications on the technical progress of radiotherapy in or close to the liver were analysed.

Results:

Most patients with cholangiocarcinoma present with unresectable disease (80–90%), and more than half of the resected patients relapse within 1 year. Adjuvant and palliative treatment options need to be chosen carefully since 50% of the patients are older than 70 years at diagnosis. Adjuvant radiotherapy or chemotherapy after complete resection (R0) has not convincingly shown a prolongation of survival but radiotherapy did after R1 resection. However, data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy in patients with marginally resectable disease. For patients with unresectable biliary tract carcinoma (BTC), palliative stenting was previously the treatment of choice. But recent SEER analyses show that radiotherapy prolongs survival, relieves symptoms and contributes to biliary decompression and should be regarded as the new standard. Novel technical advances in radiotherapy may allow for dose-escalation and could significantly improve outcome for patients with cholangiocarcinoma.

Conclusion:

Both the literature and recent technical progress corroborate the role of radiotherapy in BDC offering chances for novel clinical trials. Progress is less pronounced in chemotherapy.

Key Words

Bile duct cancer Radiotherapy Chemotherapy Chemoradiotherapy Review 

Radiotherapie und Chemotherapie als therapeutische Strategien bei extrahepatischen Gallenwegstumoren

Zusammenfassung

Ziel:

Dieser Bericht gibt eine Übersicht über die Rolle der Radio- und Chemotherapie beim extrahepatischen Gallengangskarzinom (BDC).

Patienten und Methodik:

Eine PubMed-Suche identifizierte klinische Studien zum BDT bis 1. April , 2010 und schloss randomisierte kontrollierte Studien, SEER Analysen und retrospektive Studien ein. Außerdem wurden Arbeiten zum technischen Fortschritt der Radiotherapie in und nahe der Leber analysiert.

Ergebnisse:

Die Mehrzahl der Patienten mit cholangiozellulärem Karzinom befindet sich zum Zeitpunkt der Diagnose bereits in fortgeschrittenen irresektablen Tumorstadien, und auch unter den primär operablen Patienten kommt es in den meisten Fällen zum Rezidiv innerhalb eines Jahres. Adjuvante und palliative Behandlungsoptionen müssen sorgfältig gewählt werden, weil 50% der Patienten bei Daignose älter als 70 Jahre sind. Die adjuvante Radio- bzw. Chemotherapie zeigt nach R0-Resektion keinen überzeugenden Überlebensvorteil, hingegen die Radiotherapie nach R1-Resektion. Bei sorgfältig selektierten Patientengruppen gibt es Daten zum Langzeitüberleben nach neoadjuvanter Radiochemotherapie mit anschließender Lebertransplantation. In der palliativen Situation war bislang die Einlage von Endoprothesen Methode der Wahl. Jedoch zeigen neueste SEER-Analysen, dass die Radiotherapie nicht nur eine Besserung der Lebensqualität durch Besserung der Cholestase bewirkt, nsondern auch das Überleben verlängert, weshlab sie als neue Standardtherapie angesehen werden sollte. Neueste technische Entwicklungen in der Strahlentherapie eröffnen die Perspektive einer Dosiseskalation und könnten die Ergebnisse bei Patienten mit cholangiozellulären Karzinomen dramatisch verbessern.

Schlussfolgerung:

Sowohl die Literatur als auch der jüngste technische Fortschritt stärken die Rolle der Radiotherapie beim BDC und eröffnen Chancen für klinische Studien. Für die Chemotherapie ist der Fortschritt weniger ausgeprägt.

Schlüsselwörter

Gallenwegstumoren Radiotherapie Chemotherapie Radiochemotherapie übersicht 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    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;28:945–51.CrossRefPubMedGoogle Scholar
  2. 2.
    Andre T, Tournigand C, Rosmorduc O, et al.. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study. Ann Oncol 2004;15:1339–1343.CrossRefPubMedGoogle Scholar
  3. 3.
    Ash D. Bile Duct Tumours. In: The GEC ESTRO handobook of brachytherapy (first ed.). Gerbaulet A, Pötter R, Mazeron J-J, Meertens H. van Limbergen E, eds. Brussels: The Europeans Society for Therapeutic Radiology and Oncology, 2002, pp 539-42.Google Scholar
  4. 4.
    Bowling TE, Galbraith SM, Hatfield AR, et al. A retrospective comparison of endoscopic stenting alone with stenting and radiotherapy in non-resectable cholangiocarcinoma. Gut 1996;39:852–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Brunner TB, Schwab D, Meyer T, Sauer R. Chemoradiation May Prolong Survival of Patients with Non-Bulky Unresectable Extrahepatic Biliary CarcinomaA Retrospective Analysis. Strahlenther Onkol 2004;180:751–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Buskirk SJ, Gunderson LL, Schild SE, et al. Analysis of failure after curative irradiation of extrahepatic bile duct carcinoma. Ann Surg 1992;215: 125–31.CrossRefPubMedGoogle Scholar
  7. 7.
    Cameron JL, Pitt HA, Zinner MJ, et al. Management of proximal cholangiocarcinomas by surgical resection and radiotherapy. Am J Surg 1990;159:91–7; discussion 97–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Cantore M, Mambrini A, Fiorentini G, et al. Phase II study of hepatic intraarterial epirubicin and cisplatin, with systemic 5-fluorouracil in patients with unresectable biliary tract tumors. Cancer 2005;103:1402–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Choi CW, Choi IK, Seo JH, et al. Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas. Am J Clin Oncol 2000;23:425–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Crane CH, Macdonald KO, Vauthey JN, et al. Limitations of conventional doses of chemoradiation for unresectable biliary cancer. Int J Radiat Oncol Biol Phys 2002;53:969–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Davids PH, Groen AK, Rauws EA, et al. Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet 1992;340:1488–92.CrossRefPubMedGoogle Scholar
  12. 12.
    Dawson LA, Eccles C, Craig T. Individualized image guided iso-NTCP based liver cancer SBRT. Acta Oncol (Stockholm, Sweden) 2006;45:856–64.CrossRefPubMedGoogle Scholar
  13. 13.
    Dawson LA, McGinn CJ, Normolle D, et al. Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies. J Clin Oncol 2000;18:2210–8.PubMedGoogle Scholar
  14. 14.
    Dawson LA, Normolle D, Balter JM, et al. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 2002;53:810–21.CrossRefPubMedGoogle Scholar
  15. 15.
    Dawson LA, Sharpe MB. Image-guided radiotherapy: rationale, benefits, and limitations. Lancet Oncol 2006;7:848–58.CrossRefPubMedGoogle Scholar
  16. 16.
    Deodato F, Clemente G, Mattiucci GC, et al. Chemoradiation and brachytherapy in biliary tract carcinoma: long-term results. Int J Radiat Oncol Biol Phys 2006;64:483–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Ducreux M, Rougier P, Fandi A, et al. Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin. Ann Oncol 1998;9:653–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Eccles CL, Bissonnette JP, Craig T, et al. Treatment planning study to determine potential benefit of intensity-modulated radiotherapy versus conformal radiotherapy for unresectable hepatic malignancies. Int J Radiat Oncol Biol Phys 2008;72:582–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Fields JN, Emami B. Carcinoma of the extrahepatic biliary system–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 1987;13: 331–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Figueras J, Llado L, Valls C, et al. Changing strategies in diagnosis and management of hilar cholangiocarcinoma. Liver Transpl 2000;6:786–94.PubMedGoogle Scholar
  21. 21.
    Foo ML, Gunderson LL, Bender CE, Buskirk SJ. External radiation therapy and transcatheter iridium in the treatment of extrahepatic bile duct carcinoma. Int J Radiat Oncol Biol Phys 1997;39:929–35.CrossRefPubMedGoogle Scholar
  22. 22.
    Fritz P, Brambs HJ, Schraube P, et al. Combined external beam radiotherapy and intraluminal high dose rate brachytherapy on bile duct carcinomas. Int J Radiat Oncol Biol Phys 1994;29:855–61.CrossRefPubMedGoogle Scholar
  23. 23.
    Fuller CD, Dang ND, Wang SJ, et al. Image-guided intensity-modulated radiotherapy (IG-IMRT) for biliary adenocarcinomas: Initial clinical results. Radiother Oncol 2009;92:249–54.CrossRefPubMedGoogle Scholar
  24. 24.
    Fuller CD, Wang SJ, Choi M, et al. Multimodality therapy for locoregional extrahepatic cholangiocarcinoma: a population-based analysis. Cancer 2009;115:5175–83.CrossRefPubMedGoogle Scholar
  25. 25.
    Fumex F, Coumaros D, Napoleon B, et al. Similar performance but higher cholecystitis rate with covered biliary stents: results from a prospective multicenter evaluation. Endoscopy 2006;38:787–92.CrossRefPubMedGoogle Scholar
  26. 26.
    Gerhards MF, van Gulik TM, Gonzalez Gonzalez D, et al. Results of postoperative radiotherapy for resectable hilar cholangiocarcinoma. World J Surg 2003;27:173–9.PubMedGoogle Scholar
  27. 27.
    Glimelius B, Hoffman K, Sjoden PO, et al. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 1996;7:593–600.PubMedGoogle Scholar
  28. 28.
    Grove MK, Hermann RE, Vogt DP, aBroughan TA. Role of radiation after operative palliation in cancer of the proximal bile ducts. Am J Surg 1991;161:454–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Heimbach JK, Gores GJ, Haddock MG, et al. Liver transplantation for unresectable perihilar cholangiocarcinoma. Semin Liver Dis 2004;24:201–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Hermesse J, Biver S, Jansen N, et al. A dosimetric selectivity intercomparison of HDR brachytherapy, IMRT and helical tomotherapy in prostate cancer radiotherapy. Strahlenther Onkol 2009;185:736–42.CrossRefPubMedGoogle Scholar
  31. 31.
    Hughes MA, Frassica DA, Yeo CJ, et al. Adjuvant concurrent chemoradiation for adenocarcinoma of the distal common bile duct. Int J Radiat Oncol Biol Phys 2007;68:178–82. CrossRefPubMedGoogle Scholar
  32. 32.
    Ishii H, Furuse J, Nagase M, et al. Relief of jaundice by external beam radiotherapy and intraluminal brachytherapy in patients with extrahepatic cholangiocarcinoma: results without stenting. Hepatogastroenterology 2004;51:954–7.PubMedGoogle Scholar
  33. 33.
    Iwasaki Y, Todoroki T, Fukao K, et al. The role of intraoperative radiation therapy in the treatment of bile duct cancer. World J Surg 1988;12:91–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Jarnagin WR, Ruo L, Little SA, et al. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer 2003;98:1689–700.CrossRefPubMedGoogle Scholar
  35. 35.
    Kaassis M, Boyer J, Dumas R, et al. Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study. Gastrointest Endosc 2003;57:178–82.CrossRefPubMedGoogle Scholar
  36. 36.
    Kaiser GM, Fruhauf NR, Lang H, et al. Impact of intraoperative radiotherapy (IORT) on survival of patients with unresectable hilar cholangiocarcinoma. Hepatogastroenterology 2008;55:1951–4.PubMedGoogle Scholar
  37. 37.
    Kim S, Kim SW, Bang YJ, et al. Role of postoperative radiotherapy in the management of extrahepatic bile duct cancer. Int J Radiat Oncol Biol Phys 2002;54:414–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Kopek N, Holt MI, Hansen AT, Hoyer M. Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol 2010;94:47–52.CrossRefPubMedGoogle Scholar
  39. 39.
    Kopelson G, Harisiadis L, Tretter P, Chang CH. The role of radiation therapy in cancer of the extra-hepatic biliary system: an analysis of thirteen patients and a review of the literature of the effectiveness of surgery, chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys 1977;2:883–94.CrossRefPubMedGoogle Scholar
  40. 40.
    Kuvshinoff BW, Armstrong JG, Fong Y, et al. Palliation of irresectable hilar cholangiocarcinoma with biliary drainage and radiotherapy. Br J Surg 1995;82:1522–5.CrossRefPubMedGoogle Scholar
  41. 41.
    Lu JJ, Bains YS, Abdel-Wahab M, et al. High-dose-rate remote afterloading intracavitary brachytherapy for the treatment of extrahepatic biliary duct carcinoma. Cancer J (Sudbury, Mass) 2002;8:74–8.CrossRefPubMedGoogle Scholar
  42. 42.
    McMasters KM, Tuttle TM, Leach SD, et al. Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma. Am J Surg 1997;174:605–8; discussion 608–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Nairz O, Merz F, Deutschmann H, et al A strategy for the use of image-guided radiotherapy (IGRT) on linear accelerators and its impact on treatment margins for prostate cancer patients. Strahlenther Onkol 2008;184:663–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Nehls O, Klump B, Arkenau HT, et al. Oxaliplatin, fluorouracil and leucovorin for advanced biliary system adenocarcinomas: a prospective phase II trial. Br J Cancer 2002;87:702–4.CrossRefPubMedGoogle Scholar
  45. 45.
    Nelson JW, Ghafoori AP, Willett CG, et al. Concurrent chemoradiotherapy in resected extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 2009;73:148–53.CrossRefPubMedGoogle Scholar
  46. 46.
    Niemierko A. Reporting and analyzing dose distributions: a concept of equivalent uniform dose. Med Phys 1997;24:103–10.CrossRefPubMedGoogle Scholar
  47. 47.
    Norkus D, Miller A, Kurtinaitis J, et al. A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional externalbeam radiotherapy for localized prostate adenocarcinoma : a report on acute toxicity. Strahlenther Onkol 2009;185:715–21.CrossRefPubMedGoogle Scholar
  48. 48.
    Ohnishi H, Asada M, Shichijo Y, et al. External radiotherapy for biliary decompression of hilar cholangiocarcinoma. Hepatogastroenterology 1995;42:265–8.PubMedGoogle Scholar
  49. 49.
    Park do H, Kim MH, Choi JS, et al. Covered versus uncovered wallstent for malignant extrahepatic biliary obstruction: a cohort comparative analysis. Clin Gastroenterol Hepatol 2006;4:790–6.CrossRefGoogle Scholar
  50. 50.
    Park SW, Park YS, Chung JB, et al. Patterns and relevant factors of tumor recurrence for extrahepatic bile duct carcinoma after radical resection. Hepatogastroenterology 2004;51:1612–8.PubMedGoogle Scholar
  51. 51.
    Patt YZ, Jones DV, Jr., Hoque A, et al. Phase II trial of intravenous flourouracil and subcutaneous interferon alfa-2b for biliary tract cancer. J Clin Oncol 1996;14:2311–5.PubMedGoogle Scholar
  52. 52.
    Penz M, Kornek GV, Raderer M, et al. Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer. Ann Oncol 2001;12: 183–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Pitt HA, Nakeeb A, Abrams RA, et al. Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival. Ann Surg 1995;221: 788–97; discussion 797–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Robertson JM, McGinn CJ, Walker S, et al. A phase I trial of hepatic arterial bromodeoxyuridine and conformal radiation therapy for patients with primary hepatobiliary cancers or colorectal liver metastases. Int J Radiat Oncol Biol Phys 1997;39:1087–92.CrossRefPubMedGoogle Scholar
  55. 55.
    Schoenthaler R, Phillips TL, Castro J, et al. Carcinoma of the extrahepatic bile ducts. The University of California at San Francisco experience. Ann Surg 1994;219:267–74.CrossRefPubMedGoogle Scholar
  56. 56.
    Serafini FM, Sachs D, Bloomston M, et al. Location, not staging, of cholangiocarcinoma determines the role for adjuvant chemoradiation therapy. Am Surg 2001;67:839–43; discussion 843–4.PubMedGoogle Scholar
  57. 57.
    Shinohara ET, Mitra N, Guo M, Metz JM. Radiation therapy is associated with improved survival in the adjuvant and definitive treatment of intrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 2008;72:1495–501.CrossRefPubMedGoogle Scholar
  58. 58.
    Shinohara ET, Mitra N, Guo M, Metz JM. Radiotherapy is associated with improved survival in adjuvant and palliative treatment of extrahepatic cholangiocarcinomas. Int J Radiat Oncol Biol Phys 2009;74:1191–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Soderlund C, Linder S. Covered metal versus plastic stents for malignant common bile duct stenosis: a prospective, randomized, controlled trial. Gastrointest Endosc 2006;63:986–95.CrossRefPubMedGoogle Scholar
  60. 60.
    Sterzing F, Schubert K, Sroka-Perez G, et al. Helical tomotherapy. Experiences of the first 150 patients in Heidelberg. Strahlenther Onkol 2008;184: 8–14.CrossRefPubMedGoogle Scholar
  61. 61.
    Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 2002;95:1685–95.CrossRefPubMedGoogle Scholar
  62. 62.
    Takamura A, Saito H, Kamada T, et al. Intraluminal low-dose-rate 192Ir brachytherapy combined with external beam radiotherapy and biliary stenting for unresectable extrahepatic bile duct carcinoma. Int J Radiat Oncol Biol Phys 2003;57:1357–65.CrossRefPubMedGoogle Scholar
  63. 63.
    Takeda Y, Hasuike Y, Kashiwazaki M, Tsujinaka T. Adjuvant arterial infusion chemotherapy for patients with biliary cancer. Gan to kagaku ryoho 2004;31:1835–7.PubMedGoogle Scholar
  64. 64.
    Thomas E, Chapet O, Kessler ML, et al. Benefit of using biologic parameters (EUD and NTCP) in IMRT optimization for treatment of intrahepatic tumors. Int J Radiat Oncol Biol Phys 2005;62:571–8.CrossRefPubMedGoogle Scholar
  65. 65.
    Thongprasert S. The role of chemotherapy in cholangiocarcinoma. Ann Oncol 2005;16(Suppl 2):ii93–6.Google Scholar
  66. 66.
    Todoroki T, Ohara K, Kawamoto T, et al. Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma. Int J Radiat Oncol Biol Phys 2000;46:581–7.CrossRefPubMedGoogle Scholar
  67. 67.
    Tse RV, Hawkins M, Lockwood G, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 2008;26:657–64.CrossRefPubMedGoogle Scholar
  68. 68.
    Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. New Engl J Med 2010;362:1273–81.CrossRefPubMedGoogle Scholar
  69. 69.
    Vallis KA, Benjamin IS, Munro AJ,et al. External beam and intraluminal radiotherapy for locally advanced bile duct cancer: role and tolerability. Radiother Oncol 1996;41:61–6.PubMedGoogle Scholar
  70. 70.
    Veeze-Kuijpers B, Meerwaldt JH, Lameris JS, et al. The role of radiotherapy in the treatment of bile duct carcinoma. Int J Radiat Oncol Biol Phys 1990;18:63–7.CrossRefPubMedGoogle Scholar
  71. 71.
    Wharton JT, Delclos L, Gallager S, Smith JP. Radiation hepatitis induced by abdominal irradiation with the cobalt 60 moving strip technique. Am J Roentgenol Radium Ther Nucl Med 1973;117:73–80.PubMedGoogle Scholar
  72. 72.
    Xu ZY, Liang SX, Zhu J, et al. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma. Int J Radiat Oncol Biol Phys 2006;65:189–95.CrossRefPubMedGoogle Scholar

Copyright information

© Urban & Vogel, Muenchen 2010

Authors and Affiliations

  1. 1.Gray Institute for Radiation Oncology and BiologyUniversity of OxfordOxfordUnited Kingdom
  2. 2.Gray Institute for Radiation Oncology and BiologyUniversity of OxfordOxford OX3 7LJEngland

Personalised recommendations