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REVIEW ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 1  |  Page : 10-12

Role of intraluminal brachytherapy as a palliative treatment modality in unresectable cholangiocarcinomas


Department of Radiotherapy, Geetanjali Cancer Center, Udaipur, Rajasthan, India

Date of Submission07-Oct-2019
Date of Decision25-Nov-2019
Date of Acceptance27-Jan-2020
Date of Web Publication15-Mar-2021

Correspondence Address:
Apoorv Vashistha
Medical Physicist, Department of Radiotherapy, Geetanjali Cancer Center, Geetanjali Medical College, NH 8 Bypass, Eklingpura Chouraha, Udaipur - 313 001, Rajasthan
India
Kiran Chigurupalli
Assistant Professor, Department of Radiotherapy, Geetanjali Cancer Center, Geetanjali Medical College, NH 8 Bypass, Eklingpura Chouraha, Udaipur - 313 001, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_836_19

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 > Abstract 


Cholangiocarcinoma, a primary malignant tumor of the bile ducts mainly originates from cholangiocytes. The incidence of biliary tract tumours is high in Asian countries, mainly in Thailand, India, Japan and Korea. These tumor relapse frequently and can metastsize to distant organs. Biliary stenting either by percutaneous transhepatic biliary drainage is widely used procedure used to attain symptomatic relief. Radiation therapy can be used to prevent the tumor growth in or surrounding the stent, maintaining its patency. External beam radiation therapy and intraluminal brachytherapy are the two methods by which tumoricidal doses could be delivered. Intraluminal brachytherapy can help in delivering high to the tumor while not exceeding the normal tissue tolerance of surrounding organs. In the present article we try to emphasize on the role of intra luminal brachytheraphy for palliation in advanced unresectable cholangiocarcinomas.

Keywords: Cholangiocarcinoma, Intarluminal Brachytherapy, Radiation therapy


How to cite this article:
Chigurupalli K, Vashistha A. Role of intraluminal brachytherapy as a palliative treatment modality in unresectable cholangiocarcinomas. J Can Res Ther 2021;17:10-2

How to cite this URL:
Chigurupalli K, Vashistha A. Role of intraluminal brachytherapy as a palliative treatment modality in unresectable cholangiocarcinomas. J Can Res Ther [serial online] 2021 [cited 2021 Apr 17];17:10-2. Available from: https://www.cancerjournal.net/text.asp?2021/17/1/10/311073




 > Introduction Top


Cholangiocarcinoma, a primary malignant tumor of the bile ducts mainly originates from cholangiocytes.[1] The incidence of biliary tract tumours is high in Asian countries, mainly in Thailand, India, Japan and Korea. These tumors are most commonly diagnosed in endemic areas of developing countries. In Asian countries, parasitic infestation by organisms like Clonorchis sinesis, Opisthorchis viverinni chronic infections of the biliarytract and chronic irritation by hepatolithiasis is the main cause of cholangiocarcinoma.[2] Hepatic duct bifurcation, the common hepatic duct, the ampulla and the cystic duct are the major sites from where most of the bile duct tumors arise. As the tumor spreads along the sinusoids and disruption of normal cholangioles by the tumor can cause retention of bile. These tumor relapse frequently and can metastsize to distant organs.[3]

The only curative therapy available is surgical resection. Most of the patients present in advanced stage at the time of diagnosis due to lack of symptoms. Elderly age, poor general condition, acute illness, and systemic diseases add to unresectablity of many cases.[4],[5]

Biliary stenting either by percutaneous transhepatic biliary drainage is widely used procedure used to attain symptomatic relief caused by obstructive jaundice.[6],[7] Biliary stent could be clogged due to biliary sludge, tumour growth within or surrounding the stent.[7],[8] Radiation therapy can be used to prevent the tumor growth in or surrounding the stent, maintaining its patency for a prolonged time, thus helping in the management of patient in advanced disease. Radiation therapy can also aid in treatment of cholangiocarcinomas, as they respond poorly to chemotherapy.[9]

External beam radiation therapy and intraluminal brachytherapy are the two methods by which tumoricidal doses could be delivered to the malignant area. Achieving tumoricidal doses by external beam radiation therapy is difficult because of the normal tissue tolerance of surrounding organs.[10]

Intraluminal brachytherapy can help in delivering high to the tumor while not exceeding the normal tissue tolerance of surrounding organs.[11]

In the present article we try to emphasize on the role of intra luminal brachytheraphy for palliation in advanced unresectable cholangiocarcinomas.


 > Indication For Palliative Treatment Top


Maintaining patency of stent to facilitate the flow of bile is the main objective of intraluminal brachytherapy, irrespective of the size of the tumor as the aim of the treatment is control locoregional progression along with enhancement of quality of life and improval of survival.

Intraluminal brachytherapy (ILBT) is of greater advantage in treating Klatskin tumor, a cholangiocarcinoma arising at the junction of right and left bile ducts.


 > Contra Indications Top


  1. Poor general condition
  2. Risk of radiation-induced toxicity in organs at risk.


The decision to treat by intraluminal brachytherapy for palliation should always be made individually for each and every patient. Patients with the Eastern Cooperative Oncology Group Score 0, 1 could be benefitted by the treatment.


 > Technique of Intraluminal Brachytherapy Top


ILBT can be done by percutaneous transhepatic stent technique and transduodenal endoscopic technique. Of both the techniques, percutaneous transhepatic approach is widely used.

Percutaneous transhepatic biliary stent implanted under fluoroscopy guidance is the most commonly used technique. The advantage of transhepatic catheter placement is that it provides both internal across the tumor and external drainage at the proximal end of the catheter.[2],[12],[13],[14]

Once the location and length of the tumor are identified by cholangiogram, a 10 French diameter catheter will be placed at the tumor site for biliary drainage by an interventional radiologist. Now a blind-ended brachytherapy catheter (5 French size) is passed through 10 French catheters. Once both the catheters are secured, a lead marker wire is passed through the brachytherapy catheter and computed tomography (CT) scan of 2-mm thickness is acquired. The area of interest and organs at risk are contoured and three-dimensional plans will be generated over the CT.


 > Three-Dimensional Planning Technique Top


The gross tumor volume (GTV) can be defined as tumor visualized on the CT. Clinical target volume (CTV) constitutes GTV + margin of 0.5–1 cm. Planning target volume can be generated by an additional margin of 0.5–1 cm around the CTV. The dose-limiting organs are pancreas, liver, duodenum, small bowel, stomach, and the spinal cord. Brachytherapy plan scan is generated in brachytherapy platforms like Oncentra Brachytherapy. All the dose-limiting are to be contoured for dose planning and optimization.

Doses range up to 25 Gy (4–5 Gy/fraction) in up to 5 fractions.


 > Brachytherapy Side Effects Top


Physical damage while application of catheters can cause bleeding and risk of cholangitis.

Acute complications include nausea, vomiting, and transient elevation of transaminases. Gastrointestinal bleeding, biliary bleeding, and stenosis constitute late complications.[2]


 > Results of Various Studies Top


The results of Shinohara et al. conducted on two groups, brachytherapy, and no radiotherapy revealed median survival of 11 months, as compared to 4 months (P < 0.0001) in patients who received no radiotherapy.[15]

The clinical effect of brachytherapy on stent patency and survival was evaluated on 34 patients by Chen et al. Of 34 patients, 14 patients were treated with brachytherapy. The dose of 4–7 Gy was delivered every day for 3–6 days and 3–4 times. The stent patency rate in brachytherapy was significantly long (12.6 vs. 8.3 months, P < 0.05). The mean survival was higher in the brachytherapy group, but not significant (9.4 vs. 6 months).[16]

The Phase-I study results of Mattiucci et al., Singh et al. revealed longer patency of stent and better survival of patients. In the study patients were treated with ILBT where 25 Gy in 5 fractions was delivered, after stenting. Their intent of treatment was palliation.[17],[18]

Skowronek et al. used brachytherapy as monotherapy for palliation. They found that pulse dose rate-brachytherapy using 20 Gy (pulse 0.8 Gy every h/cm) 19/29 patients, jaundice level started to decrease after 4 weeks. These patients also had an overall survival of 11.2 months.[13]

Yoshioka et al. reported the addition of ILBT to external beam radiation therapy (EBRT), did not impact overall survival or disease-free survival, but the addition of brachytherapy resulted in much better local control. The 2-year local control rates were 65% in the EBRT + ILBT group and 35% in EBRT only group. They recommended to address the role of brachytherapy in terms of maintaining stent patency, benefit in toxicity and quality of life.[19]


 > Conclusions Top


Intraluminal brachytherapy could play an important role in the multimodality approach to bile duct carcinomas. It provides a better platform to deliver high dose of radiation to tumor and minimizing dose to organs at risk. Brachytherapy can be used for palliation to maintain the outflow of bile in unresectable tumors. Brachytherapy can improve local control, enhance survival, and quality of life.[13],[15],[16],[17],[18],[19]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Lazaridis KN, Gores GJ. Cholangiocarcinoma. Gastroenterology 2005;128:1655-67.  Back to cited text no. 1
    
2.
Cheng SH, Huang AT. Liver and Hepatobiliary Tract. In: Halperin EC, Perez CA, Brady LW, editors. Perez and Brady's Principles and Practice of Radiation Oncology. 5th ed., Ch. 57. Philadelphia: Lippincott Williams & Wilkins; 2008.  Back to cited text no. 2
    
3.
Skowronek J, Zwierzchowski G. Brachytherapy in the treatment of bile duct cancer: A tough challenge. J Contemp Brachytherapy 2017;9:187-95.  Back to cited text no. 3
    
4.
Gibby DG, Hanks JB, Wanebo HJ, Kaiser DL, Tegtmeyer CJ, Chandler JG, et al. Bile duct carcinoma. Diagnosis and treatment. Ann Surg 1985;202:139-44.  Back to cited text no. 4
    
5.
Yeo CJ, Pitt HA, Cameron JL. Cholangiocarcinoma. Surg Clin North Am 1990;70:1429-47.  Back to cited text no. 5
    
6.
Lee CK, Barrios BR, Bjarnason H. Biliary tree malignancies: The University of Minnesota experience. J Surg Oncol 1997;65:298-305.  Back to cited text no. 6
    
7.
Erickson BA, Nag S. Biliar y tree malignancies. J Surg Oncol 1998;67:203-10.  Back to cited text no. 7
    
8.
Jaganmohan S, Lee JH. Self-expandable metal stents in malignant biliary obstruction. Expert Rev Gastroenterol Hepatol 2012;6:105-14.  Back to cited text no. 8
    
9.
Ramírez-Merino N, Aix SP, Cortés-Fune H. Chemotherapy for cholangiocarcinoma: An update. World J Gastrointest Oncol 2013;5:171-6.  Back to cited text no. 9
    
10.
Shin HS, Seong J, Kim WC, Shin HS, Seong J, Kim WC, et al. Combination of external beam irradiation and high-dose-rate intraluminal brachytherapy for inoperable carcinoma of the extrahepatic bile ducts. Int J Radiat Oncol Biol Phys 2003;57:105-12.  Back to cited text no. 10
    
11.
Kamada T, Saitou H, Takamura A, Nojima T, Okushiba SI. The role of radiotherapy in the management of extrahepatic bile duct cancer: An analysis of 145 consecutive patients treated with intraluminal and/or external beam radiotherapy. Int J Radiat Oncol Biol Phys 1996;34:767-74.  Back to cited text no. 11
    
12.
Skowronek J, Sowier A, Skrzywanek P. Intraluminal pulsed dose rate (PDR) brachytherapy and trans-hepatic technique in treatment of locally advanced bile duct cancer – Preliminary assessment. Rep Pract Radioth Oncol 2007;2:125-33.  Back to cited text no. 12
    
13.
Skowronek J, Sowier A, Skrzywanek P. Trans-hepatic technique and intraluminal pulsed dose rate (PDR-BT) brachytherapy in treatment of locally advanced bile duct and pancreas cancer. J Contemp Brachytherapy 2009;1:97-104.  Back to cited text no. 13
    
14.
Yamaguchi K, Chijiiwa K, Saiki S, Shimizu S, Takashima M, Tanaka M. Carcinoma of the extrahepatic bile duct: Mode of spread and its prognostic implications. Hepatogastroenterology 1997;44:1256-61.  Back to cited text no. 14
    
15.
Shinohara ET, Guo M, Mitra N, Metz JM. Brachytherapy in the treatment of cholangiocarcinoma. Int J Radiat Oncol Biol Phys 2010;78:722-8.  Back to cited text no. 15
    
16.
Chen Y, Wang XL, Yan ZP, Cheng JM, Wang JH, Gong GQ, et al. HDR-192Ir intraluminal brachytherapy in treatment of malignant obstructive jaundice. World J Gastroenterol 2004;10:3506-10.  Back to cited text no. 16
    
17.
Mattiucci GC, Autorino R, Tringali A, Perri V, Balducci M, Deodato F, et al. A Phase I study of high-dose-rate intraluminal brachytherapy as palliative treatment in extrahepatic biliary tract cancer. Brachytherapy 2015;14:401-4.  Back to cited text no. 17
    
18.
Singh V, Kapoor R, Solanki KK, Singh G, Verma GR, Sharma SC. Endoscopic intraluminal brachytherapy and metal stents in malignant hilar biliary obstruction: A pilot study. Liver Int 2007;27:347-52.  Back to cited text no. 18
    
19.
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;89:822-9.  Back to cited text no. 19
    




 

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