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Digestive Disease Interventions 2020; 04(01): 060-066
DOI: 10.1055/s-0040-1705093
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Radiation Therapy for Cholangiocarcinoma

Sarah M.C. Sittenfeld
1   Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
,
James R. Broughman
1   Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
,
Shauna R. Campbell
1   Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
,
Kevin L. Stephans
1   Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
› Author Affiliations
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Publication History

16 November 2019

03 January 2020

Publication Date:
02 March 2020 (online)

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Abstract

Cholangiocarcinoma (CC) is a rare disease representing only 3% of the primary gastrointestinal malignancies. CC is classified based on anatomical location (intrahepatic, perihilar, and extrahepatic) and surgery is the preferred definitive treatment, regardless of location. However, a minority of patients is able to undergo complete surgical resection, and thus, nonsurgical locoregional therapy is imperative for tumor control. With the significant evolution of external beam radiation therapy, higher doses can be more precisely delivered, with adequate sparing of surrounding normal tissues, which appear to be associated with improved outcomes. In this review, we discuss the role of radiation therapy for each anatomical subsite of CC including the postoperative setting, neoadjuvant setting prior to liver transplantation, as well as definitive treatment with dose-escalated radiation and stereotactic body radiation therapy. Although there has been substantial improvement in radiation therapy techniques, randomized data are limited given CC remains both a rare and heterogenous disease. A multidisciplinary approach to treatment is essential in order to achieve optimal outcomes, and further investigation into novel therapies remains ongoing.

Keywords

cholangiocarcinoma - radiation therapy - SBRT
 

  • References

  • 1 Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 2013; 145 (06) 1215-1229
    CrossrefPubMedGoogle Scholar
  • 2 Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma—evolving concepts and therapeutic strategies. Nat Rev Clin Oncol 2018; 15 (02) 95-111
    CrossrefPubMedGoogle Scholar
  • 3 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 (03) 219-226
    PubMedGoogle Scholar
  • 4 Choi HS, Kang KM, Jeong BK. , et al. Patterns of failure after resection of extrahepatic bile duct cancer: implications for adjuvant radiotherapy indication and treatment volumes. Radiat Oncol 2018; 13 (01) 85
    CrossrefPubMedGoogle Scholar
  • 5 Koo TR, Eom KY, Kim IA. , et al. Patterns of failure and prognostic factors in resected extrahepatic bile duct cancer: implication for adjuvant radiotherapy. Radiat Oncol J 2014; 32 (02) 63-69
    CrossrefPubMedGoogle Scholar
  • 6 Kim J-S, Koo TR. Analysis of patterns of failure and prognostic factors in resected extrahepatic bile duct cancer: implications for postoperative adjuvant radiotherapy. J Clin Oncol 2013; 31 (04) 266
    PubMedGoogle Scholar
  • 7 Ben-David MA, Griffith KA, Abu-Isa E. , et al. External-beam radiotherapy for localized extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 2006; 66 (03) 772-779
    CrossrefPubMedGoogle Scholar
  • 8 Kim S, Kim SW, Bang YJ, Heo DS, Ha SW. Role of postoperative radiotherapy in the management of extrahepatic bile duct cancer. Int J Radiat Oncol Biol Phys 2002; 54 (02) 414-419
    CrossrefPubMedGoogle Scholar
  • 9 Schoenthaler R, Phillips TL, Castro J, Efird JT, Better A, Way LW. Carcinoma of the extrahepatic bile ducts. The University of California at San Francisco experience. Ann Surg 1994; 219 (03) 267-274
    CrossrefPubMedGoogle Scholar
  • 10 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 (03) 581-587
    CrossrefPubMedGoogle Scholar
  • 11 Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol 2012; 30 (16) 1934-1940
    CrossrefPubMedGoogle Scholar
  • 12 Ben-Josef E, Guthrie KA, El-Khoueiry AB. , et al. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol 2015; 33 (24) 2617-2622
    CrossrefPubMedGoogle Scholar
  • 13 Yang H, Zhou J, Wei X, Wang F, Zhao H, Li E. Survival outcomes and prognostic factors of extrahepatic cholangiocarcinoma patients following surgical resection: adjuvant therapy is a favorable prognostic factor. Mol Clin Oncol 2014; 2 (06) 1069-1075
    CrossrefPubMedGoogle Scholar
  • 14 DeOliveira ML, Cunningham SC, Cameron JL. , et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 2007; 245 (05) 755-762
    CrossrefPubMedGoogle Scholar
  • 15 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 (01) 117-122
    CrossrefPubMedGoogle Scholar
  • 16 Sudan D, DeRoover A, Chinnakotla S. , et al. Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant 2002; 2 (08) 774-779
    CrossrefPubMedGoogle Scholar
  • 17 Rosen CB, Heimbach JK, Gores GJ. Surgery for cholangiocarcinoma: the role of liver transplantation. HPB (Oxford) 2008; 10 (03) 186-189
    CrossrefPubMedGoogle Scholar
  • 18 Darwish Murad S, Kim WR, Harnois DM. , et al. Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology 2012; 143 (01) 88-98.e3 , quiz e14
    CrossrefPubMedGoogle Scholar
  • 19 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 2002; 8 (01) 74-78
    CrossrefPubMedGoogle Scholar
  • 20 Mukewar S, Gupta A, Baron TH. , et al. Endoscopically inserted nasobiliary catheters for high dose-rate brachytherapy as part of neoadjuvant therapy for perihilar cholangiocarcinoma. Endoscopy 2015; 47 (10) 878-883
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Broughman J, Sittenfeld S, Bauer-Nilsen K, Stephans K. Substituting stereotactic body radiation therapy boost for brachytherapy in Mayo protocol for peri-hilar cholangiocarcinoma. Appl Radiation Oncol 2019; 8 (03) 43-45
    PubMedGoogle Scholar
  • 22 Darwish Murad S, Kim WR, Therneau T. , et al. Predictors of pretransplant dropout and posttransplant recurrence in patients with perihilar cholangiocarcinoma. Hepatology 2012; 56 (03) 972-981
    CrossrefPubMedGoogle Scholar
  • 23 Lehrke HD, Heimbach JK, Wu TT. , et al. Prognostic significance of the histologic response of perihilar cholangiocarcinoma to preoperative neoadjuvant chemoradiation in liver explants. Am J Surg Pathol 2016; 40 (04) 510-518
    CrossrefPubMedGoogle Scholar
  • 24 Sio TT, Martenson Jr JA, Haddock MG. , et al. Outcome of transplant-fallout patients with unresectable cholangiocarcinoma. Am J Clin Oncol 2016; 39 (03) 271-275
    CrossrefPubMedGoogle Scholar
  • 25 Welling TH, Feng M, Wan S. , et al. Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma. Liver Transpl 2014; 20 (01) 81-88
    CrossrefPubMedGoogle Scholar
  • 26 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 (04) 969-974
    CrossrefPubMedGoogle Scholar
  • 27 Miften M, Vinogradskiy Y, Moiseenko V. , et al. Radiation dose-volume effects for liver SBRT. Int J Radiat Oncol Biol Phys 2018 (e-pub ahead of print) Doi: 10.1016/j.ijrobp.2017.12.290
    PubMedGoogle Scholar
  • 28 Dawson LA. RTOG 1112: Randomized phase III study of sorafenib versus stereotactic body radiation therapy followed by sorafenib in hepatocellular carcinoma. Available at: https://www.rtog.org/Portals/0/RTOG%20Broadcasts/Attachments/1112_master_w_update_5.7.13.pdf . Published 2012. Accessed November 21, 2019
    PubMedGoogle Scholar
  • 29 Pollom EL, Chin AL, Diehn M, Loo BW, Chang DT. Normal tissue constraints for abdominal and thoracic stereotactic body radiotherapy. Semin Radiat Oncol 2017; 27 (03) 197-208
    CrossrefPubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar
  • 31 Momm F, Schubert E, Henne K. , et al. Stereotactic fractionated radiotherapy for Klatskin tumours. Radiother Oncol 2010; 95 (01) 99-102
    CrossrefPubMedGoogle Scholar
  • 32 Kopek N, Holt MI, Hansen AT, Høyer M. Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol 2010; 94 (01) 47-52
    CrossrefPubMedGoogle Scholar
  • 33 Polistina FA, Guglielmi R, Baiocchi C. , 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 (02) 120-123
    CrossrefPubMedGoogle Scholar
  • 34 Groot Koerkamp B, Wiggers JK, Allen PJ. , et al. Recurrence rate and pattern of perihilar cholangiocarcinoma after curative intent resection. J Am Coll Surg 2015; 221 (06) 1041-1049
    CrossrefPubMedGoogle Scholar
  • 35 Thomas TO, Hasan S, Small Jr W. , et al. The tolerance of gastrointestinal organs to stereotactic body radiation therapy: what do we know so far?. J Gastrointest Oncol 2014; 5 (03) 236-246
    PubMedGoogle Scholar
  • 36 Emami B, Lyman J, Brown A. , et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991; 21 (01) 109-122
    PubMedGoogle Scholar
  • 37 Hong TS, Wo JY, 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 (05) 460-468
    PubMedGoogle Scholar
  • 38 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 2019 (e-pub ahead of print). Doi: 10.1001/jamaoncol.2019.3702
    PubMedGoogle Scholar
  • 39 Campbell SR, Juloori A, LaHurd D. , et al. Evaluating safety and dosimetry of SBRT following 90Y for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2018; 102 (03) e51
    PubMedGoogle Scholar
  • 40 Feng M, Suresh K, Schipper MJ. , et al. Individualized adaptive stereotactic body radiotherapy for liver tumors in patients at high risk for liver damage: a phase 2 clinical trial. JAMA Oncol 2018; 4 (01) 40-47
    CrossrefPubMedGoogle Scholar