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DOI: 10.1055/s-0044-1788557
Management of Unresectable Cholangiocarcinoma Using Modern Radiation Therapy Techniques
Abstract
Cholangiocarcinoma (CCA) is a malignancy of epithelial cells in the bile duct, categorized based on its anatomical location as intrahepatic, perihilar, or extrahepatic. It has a low prevalence of ∼1.6 cases per 100,000 people in the United States, but has a poor prognosis. All stages included, CCA has a 5-year survival rate of less than 10%. The preferred curative treatment for intrahepatic, perihilar, and extrahepatic CCA is surgical resection combined with systemic chemotherapy. However, resection is not always a viable option for many patients, as the disease is often discovered at the time of diagnosis to be either metastatic or locally advanced precluding surgical resection. In this setting, a variety of options can be used, one of which is radiation therapy (RT). The administration of RT has evolved tremendously over the past decades. Total doses given can be limited by a tumor's proximity to regional normal organs such as the liver, stomach, bile duct, and small and large bowel. When a CCA is unresectable, it is often in close proximity to radiosensitive organs. Delivering RT in this setting therefore requires precise delivery techniques. An emerging technique known broadly as stereotactic body radiation therapy (SBRT) or stereotactic ablative body radiation therapy gives a highly focused, often ablative, form of RT to a defined and specific target. Categorically, SBRT offers a quick and efficient management option, in some cases only one to three total treatments. This narrative reviews various applications of SBRT for cholangiocarcinoma including SBRT alone, SBRT with chemotherapy, SBRT with chemotherapy followed by a liver transplantation (orthotopic liver transplantation), and finally novel combinations of SBRT with immunotherapy.
Publication History
Received: 28 April 2024
Accepted: 24 June 2024
Article published online:
17 July 2024
© 2024. Thieme. All rights reserved.
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References
- 1 Brindley PJ, Bachini M, Ilyas SI. et al. Cholangiocarcinoma. Nat Rev Dis Primers 2021; 7 (01) 65
- 2 Banales JM, Cardinale V, Carpino G. et al. Expert consensus document: cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol 2016; 13 (05) 261-280
- 3 Ilyas SI, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 2013; 145 (06) 1215-1229
- 4 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
- 5 Clements O, Eliahoo J, Kim JU, Taylor-Robinson SD, Khan SA. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a systematic review and meta-analysis. J Hepatol 2020; 72 (01) 95-103
- 6 Cillo U, Fondevila C, Donadon M. et al. Surgery for cholangiocarcinoma. Liver Int 2019; 39 (Suppl, Suppl 1): 143-155
- 7 Hoehn RS, Wima K, Ertel AE. et al. Adjuvant chemotherapy and radiation therapy is associated with improved survival for patients with extrahepatic cholangiocarcinoma. Ann Surg Oncol 2015; 22 (Suppl. 03) S1133-S1139
- 8 Ecker BL, Vining CC, Roses RE. et al. Identification of patients for adjuvant therapy after resection of carcinoma of the extrahepatic bile ducts: a propensity score-matched analysis. Ann Surg Oncol 2017; 24 (13) 3926-3933
- 9 Dover LL, Oster RA, McDonald AM, DuBay DA, Wang TN, Jacob R. Impact of adjuvant chemoradiation on survival in patients with resectable cholangiocarcinoma. HPB (Oxford) 2016; 18 (10) 843-850
- 10 Kim YS, Oh SY, Go SI. et al. The role of adjuvant therapy after R0 resection for patients with intrahepatic and perihilar cholangiocarcinomas. Cancer Chemother Pharmacol 2017; 79 (01) 99-106
- 11 Kim YS, Hwang IG, Park SE. et al. Role of adjuvant therapy after R0 resection for patients with distal cholangiocarcinoma. Cancer Chemother Pharmacol 2016; 77 (05) 979-985
- 12 Kopek N, Holt MI, Hansen AT, Høyer M. Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol 2010; 94 (01) 47-52
- 13 Duignan S, Maguire D, Ravichand CS. et al. Neoadjuvant chemoradiotherapy followed by liver transplantation for unresectable cholangiocarcinoma: a single-centre national experience. HPB (Oxford) 2014; 16 (01) 91-98
- 14 Brunner TB, Blanck O, Lewitzki V. et al. Stereotactic body radiotherapy dose and its impact on local control and overall survival of patients for locally advanced intrahepatic and extrahepatic cholangiocarcinoma. Radiother Oncol 2019; 132: 42-47
- 15 Kavanagh BD, McGarry RC, Timmerman RD. Extracranial radiosurgery (stereotactic body radiation therapy) for oligometastases. Semin Radiat Oncol 2006; 16 (02) 77-84
- 16 Lee J, Yoon WS, Koom WS, Rim CH. Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review. Strahlenther Onkol 2019; 195 (02) 93-102
- 17 Potters L, Kavanagh B, Galvin JM. et al; American Society for Therapeutic Radiology and Oncology, American College of Radiology. American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the performance of stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 2010; 76 (02) 326-332
- 18 Haridass A. Developments in stereotactic body radiotherapy. Cancers (Basel) 2018; 10 (12) 497
- 19 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
- 20 Mahadevan A, Dagoglu N, Mancias J. et al. Stereotactic body radiotherapy (SBRT) for intrahepatic and hilar cholangiocarcinoma. J Cancer 2015; 6 (11) 1099-1104
- 21 Cheng Y, Lin Y, Long Y. et al. Is the CyberKnife© radiosurgery system effective and safe for patients? An umbrella review of the evidence. Future Oncol 2022; 18 (14) 1777-1791
- 22 Zhang XX, Ma HB, Li TH, Huang B, Jia NY, Meng Y. Actual over 3-year survival after stereotactic body radiation therapy in patients with unresectable intrahepatic cholangiocarcinoma. Clin Transl Oncol 2023; 25 (03) 731-738
- 23 Weiner AA, Olsen J, Ma D. et al. Stereotactic body radiotherapy for primary hepatic malignancies - report of a phase I/II institutional study. Radiother Oncol 2016; 121 (01) 79-85
- 24 Gkika E, Hallauer L, Kirste S. et al. Stereotactic body radiotherapy (SBRT) for locally advanced intrahepatic and extrahepatic cholangiocarcinoma. BMC Cancer 2017; 17 (01) 781
- 25 Sandler KA, Veruttipong D, Agopian VG. et al. Stereotactic body radiotherapy (SBRT) for locally advanced extrahepatic and intrahepatic cholangiocarcinoma. Adv Radiat Oncol 2016; 1 (04) 237-243
- 26 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
- 27 Jung DH, Kim MS, Cho CK. et al. Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma. Radiat Oncol J 2014; 32 (03) 163-169
- 28 Shen ZT, Zhou H, Li AM, Li B, Shen JS, Zhu XX. Clinical outcomes and prognostic factors of stereotactic body radiation therapy for intrahepatic cholangiocarcinoma. Oncotarget 2017; 8 (55) 93541-93550
- 29 Sebastian NT, Tan Y, Miller ED, Williams TM, Alexandra Diaz D. Stereotactic body radiation therapy is associated with improved overall survival compared to chemoradiation or radioembolization in the treatment of unresectable intrahepatic cholangiocarcinoma. Clin Transl Radiat Oncol 2019; 19: 66-71
- 30 Torgeson A, Lloyd S, Boothe D. et al. Chemoradiation therapy for unresected extrahepatic cholangiocarcinoma: a propensity score-matched analysis. Ann Surg Oncol 2017; 24 (13) 4001-4008
- 31 Cho Y, Kim TH, Seong J. Improved oncologic outcome with chemoradiotherapy followed by surgery in unresectable intrahepatic cholangiocarcinoma. Strahlenther Onkol 2017; 193 (08) 620-629
- 32 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
- 33 Wu TC, Deng J, Chu FI. et al. Single center experience using stereotactic body radiation therapy (SBRT) on orthotopic liver transplant protocol for unresectable cholangiocarcinoma. HPB (Oxford) 2024; 26 (03) 444-450
- 34 Ziogas IA, Giannis D, Economopoulos KP. et al. Liver transplantation for intrahepatic cholangiocarcinoma: a meta-analysis and meta-regression of survival rates. Transplantation 2021; 105 (10) 2263-2271
- 35 Hong JC, Jones CM, Duffy JP. 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 (06) 683-689
- 36 Wong M, Kim J, George B. et al. Downstaging locally advanced cholangiocarcinoma pre-liver transplantation: a prospective pilot study. J Surg Res 2019; 242: 23-30
- 37 Wu TC, Smith CP, Li JS. et al. A systematic review and meta-analysis of pathologic complete response rates for patients with cholangiocarcinoma treated on liver transplant protocols. J Surg Oncol 2024; 129 (03) 574-583
- 38 Liu X, Yao J, Song L, Zhang S, Huang T, Li Y. Local and abscopal responses in advanced intrahepatic cholangiocarcinoma with low TMB, MSS, pMMR and negative PD-L1 expression following combined therapy of SBRT with PD-1 blockade. J Immunother Cancer 2019; 7 (01) 204
- 39 Zhao Q, Chen Y, Du S. et al. Integration of radiotherapy with anti-PD-1 antibody for the treatment of intrahepatic or hilar cholangiocarcinoma: reflection from four cases. Cancer Biol Ther 2021; 22 (03) 175-183
- 40 Kreidieh M, Zeidan YH, Shamseddine A. The combination of stereotactic body radiation therapy and immunotherapy in primary liver tumors. J Oncol 2019; 2019: 4304817
- 41 Jiang J, Diaz DA, Nuguru SP, Mittra A, Manne A. Stereotactic body radiation therapy (SBRT) plus immune checkpoint inhibitors (ICI) in hepatocellular carcinoma and cholangiocarcinoma. Cancers (Basel) 2022; 15 (01) 50
- 42 Kelley RK, Ueno M, Yoo C. et al; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023; 401 (10391): 1853-1865
- 43 Zhu C, Li H, Yang X. et al. Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study. Cancer Immunol Immunother 2023; 72 (09) 2949-2960
- 44 Elias C, Zeidan YH, Bouferraa Y. et al. A phase II single arm study of Nivolumab with stereotactic Ablative radiation Therapy after induction chemotherapy in CHOlangiocarcinoma (NATCHO). BMC Cancer 2022; 22 (01) 1296