Clinical Investigation
Brachytherapy in the Treatment of Cholangiocarcinoma

https://doi.org/10.1016/j.ijrobp.2009.08.070Get rights and content

Purpose

To examine the role of brachytherapy in the treatment of cholangiocarcinomas in a relatively large group of patients.

Methods and Materials

Using the Surveillance, Epidemiology and End Results database, a total of 193 patients with cholangiocarcinoma treated with brachytherapy were identified for the period 1988–2003. The primary analysis compared patients treated with brachytherapy (with or without external-beam radiation) with those who did not receive radiation. To try to account for confounding variables, propensity score and sensitivity analyses were used.

Results

There was a significant difference between patients who received radiation (n = 193) and those who did not (n = 6859) with regard to surgery (p < 0.0001), race (p < 0.0001), stage (p < 0.0001), and year of diagnosis (p <0.0001). Median survival for patients treated with brachytherapy was 11 months (95% confidence interval [CI] 9–13 months), compared with 4 months for patients who received no radiation (p < 0.0001). On multivariable analysis (hazard ratio [95% CI]) brachytherapy (0.79 [0.66–0.95]), surgery (0.50 [0.46–0.53]), year of diagnosis (1998–2003: 0.66 [0.60–0.73]; 1993–1997: (0.96 [0.89–1.03; NS], baseline 1988–1992), and extrahepatic disease (0.84 [0.79–0.89]) were associated with better overall survival.

Conclusions

To the authors' knowledge, this is the largest dataset reported for the treatment of cholangiocarcinomas with brachytherapy. The results of this retrospective analysis suggest that brachytherapy may improve overall survival. However, because of the limitations of the Surveillance, Epidemiology and End Results database, these results should be interpreted cautiously, and future prospective studies are needed.

Introduction

Cholangiocarcinomas are rare malignancies that arise from the epithelial cells that line the bile ducts and constitute approximately 3% of all gastrointestinal cancers (1). Surgical resection is the only curative treatment for cholangiocarcinomas; however, a large proportion of patients are unresectable at the time of diagnosis 2, 3, 4, 5, 6. Optimal adjuvant therapy for resected patients and palliative treatment for unresectable patients remains unclear. Evidence to support treatment recommendations is scant, in large part owing to the low incidence of cholangiocarcinomas, which has precluded large randomized studies examining the role of radiation and chemotherapy.

Brachytherapy is one way radiation can be used to treat cholangiocarcinoma and may improve stent patency and perhaps improve survival 7, 8, 9, 10, 11, 12. Because of the intraluminal growth pattern, positive margins are often seen at the cut biliary duct margin, which may be treated with brachytherapy. Brachytherapy has many advantages in that it allows the delivery of localized radiation that may limit toxicity and allow dose escalation. Hence, brachytherapy can potentially be used as a boost to safely increase the dose delivered in the definitive setting.

It is also important to maintain biliary patency because most patients ultimately die of liver dysfunction due to tumor obstruction of biliary drainage. Some studies have found that biliary stenting is as effective as surgical bypass in providing relief from obstructive jaundice (13). Even in patients with unresectable pancreatic cancer or cholangiocarcinoma, approximately 21% will be alive at 1 year. Hence, long-term solutions for malignant obstructive jaundice are needed, because many patients will survive long enough that reocclusion will be a major problem, even in the setting of unresectable disease (14). Brachytherapy may improve the duration of stent patency and potentially extend survival (15).

The majority of studies that have examined the use of brachytherapy in cholangiocarcinomas are small single-institution studies. In the present study a retrospective analysis of a large group of patients with extrahepatic cholangiocarcinoma (EHC) and intrahepatic cholangiocarcinoma (IHC) treated with brachytherapy was performed using the Surveillance, Epidemiology and End Results (SEER) database.

Section snippets

Patient selection and treatment

The SEER database is a national cancer surveillance program run by the National Cancer Institute that collects information about the incidence and survival of cancer cases from 17 cancer registries throughout the United States. These registries encompass approximately 26% of the United States population and are representative of national demographics. The SEER database was queried for the diagnosis of cholangiocarcinoma from 1988 to 2003. The International Classification of Diseases for

Results

A total of 5345 patients with EHC and 4359 patients with IHC with radiation and surgical data were identified for the period 1988–2003. Of these patients, a total of 43 (0.60% of all patients in this study) were treated with brachytherapy alone, and 150 patients (2.1% of all patients in this study) were treated with a combination of external-beam radiation and brachytherapy. A total of 6859 patients received no radiation. Because of the relatively small number of patients treated with

Discussion

The present study investigates the use of brachytherapy in a large group of patients with cholangiocarcinoma from the SEER database. Results from this analysis demonstrate an improvement in OS when patients were treated with brachytherapy with or without external-beam radiation compared with patients treated without radiation. Subset analysis comparing brachytherapy alone vs. no radiation and brachytherapy combined with external beam radiation vs. no radiation suggested that the survival

References (34)

  • J.N. Vauthey et al.

    Recent advances in the management of cholangiocarcinomas

    Semin Liver Dis

    (1994)
  • J.C. Tan et al.

    Surgical management of intrahepatic cholangiocarcinoma: A population-Based study

    Ann Surg Oncol

    (2008)
  • A. Nakeeb et al.

    Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors

    Ann Surg

    (1996)
  • Y. Murakami et al.

    Prognostic significance of lymph node metastasis and surgical margin status for distal cholangiocarcinoma

    J Surg Oncol

    (2007)
  • H. Malhi et al.

    Review article: The modern diagnosis and therapy of cholangiocarcinoma

    Aliment Pharmacol Ther

    (2006)
  • X.J. Qian et al.

    Treatment of malignant biliary obstruction by combined percutaneous transhepatic biliary drainage with local tumor treatment

    World J Gastroenterol

    (2006)
  • Z. Kocak et al.

    Intraluminal brachytherapy with metallic stenting in the palliative treatment of malignant obstruction of the bile duct

    Radiat Med

    (2005)
  • Cited by (41)

    • Principles and indications of brachytherapy

      2022, Nuclear Medicine and Molecular Imaging: Volume 1-4
    • The combination of endoluminal radiofrequency ablation and metal stent implantation for the treatment of malignant biliary stenosis – Randomized study

      2021, European Journal of Radiology
      Citation Excerpt :

      Chen et al. in his study achieved a prolonged stent patency rate in the group treated with brachytherapy (12.6 vs 8.3 months), but extended survival did not reach a statistically significant level (median 7.0 vs 6.0 months) [4]. Shinohara et al. in 2010 showed an increased survival rate in brachytherapy group compared to the control group (11 vs 4 months) [5]. Endoluminal radiofrequency ablation (RFA) performed before biliary metal stent placement benefits from its simplicity of use and patient management.

    • High-dose rate intraluminal brachytherapy: An effective palliation for cholangiocarcinoma causing bile duct obstruction

      2018, Surgical Oncology
      Citation Excerpt :

      Most of these patients will eventually experience biliary obstruction during the course of their disease and as a result, disabling jaundice, intense pruritus, loss of appetite and weight, acholic stools, painful hepatomegaly, change in bowel habits, nausea, vomiting, coagulopathies and even cholangitis and sepsis [4]. Restoration of bile flow is thus required to prevent complications and because most patients ultimately die of liver dysfunction due to tumour obstruction of biliary drainage [6]. Multiple palliative treatment options are available, such as endoscopic retrograde biliary drainage through sphincterotomy and/or stent placement [7], percutaneous anterograde drainage [8], external beam radiation [9,10], intraluminal brachytherapy (ILBT) [4], palliative chemotherapy [11], surgery [12], photodynamic therapy (PDT) [13] or a combination of these modalities.

    • Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: A multicenter trial

      2018, Journal of Hepatology
      Citation Excerpt :

      Theoretically, the four lines of radioactive seeds used by the new device in this study should improve dosimetry compared to brachytherapy, with a tube shaking in the biliary tract, described in previous reports. The estimated median radiation dose in this study at the dose reference points calculated by the computerized TPS was approximately 47.0 Gy, which is between the reported dose of 25.0 to 70.0 Gy in traditional brachytherapy with other radioactive sources.36,37 None of brachytherapy-related grade 3 or 4 complications was found in this trial.

    • Cholangiocarcinoma

      2017, Zakim and Boyer's Hepatology: A Textbook of Liver Disease
    • Hepatobiliary Cancer

      2015, Clinical Radiation Oncology
    View all citing articles on Scopus

    This project was funded, in part, under a grant with the Pennsylvania Department of Health. The Department specifically disclaims responsibility for any analysis, interpretations, or conclusions.

    Conflict of interest: none.

    View full text