Clinical Investigation
Radiotherapy Is Associated With Improved Survival in Adjuvant and Palliative Treatment of Extrahepatic Cholangiocarcinomas

https://doi.org/10.1016/j.ijrobp.2008.09.017Get rights and content

Purpose

Extrahepatic cholangiocarcinomas (EHC) are rare tumors of the biliary tree because of their low incidence, large randomized studies examining radiotherapy (RT) for EHC have not been performed. The purpose of this study was to examine the role of adjuvant and palliative RT in the treatment of EHC in a large patient population.

Methods and Materials

This was a retrospective analysis of 4,758 patients with EHC collected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was overall survival.

Results

Patients underwent surgery (28.8%), RT (10.0%), surgery and RT (14.7%), or no RT or surgery (46.4%). The median age of the patient population was 73 years (range, 23–104), 52.5% were men, and 80.7% were white. The median overall survival time was 16 months (95% confidence interval [CI] 15–17), 9 months (95% CI 9–11), 9 months (95% CI 9–10), and 4 months (95% CI 3–4) for surgery and RT, surgery, RT, and no RT or surgery, respectively. The overall survival was significantly different between the surgery and surgery and RT groups (p < .0001) and RT and no RT or surgery groups (p < .0001) on the log–rank test. The propensity score-adjusted analyses of surgery and RT vs. surgery (hazard ratio, 0.94; 95% CI, 0.84–1.05) were not significantly different, but that for RT vs. no RT or surgery (hazard ratio, 0.61; 95% CI, 0.54–0.70) was significantly different.

Conclusion

These results suggest that palliative RT prolongs survival in patients with EHC. The benefit associated with surgery and RT was significant on univariate analysis but not after controlling for potential confounders using the propensity score. Future studies should evaluate the addition of chemotherapy and biologic agents for the treatment of EHC.

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). Cholangiocarcinomas can be classified by their location within the biliary tree as intrahepatic, hilar (Klatskin's tumor), or distal, each with different resectability rates and outcomes. Whether this is because of a biologic difference dependent on tumor location is under debate (2). The present study focused on the use of radiotherapy (RT) for extrahepatic cholangiocarcinoma (EHC). Distal EHCs constitute approximately 20–30% of cholangiocarcinomas, with hilar cholangiocarcinomas accounting for an additional 50–60% (3). The incidence of EHCs appears to be decreasing; however, approximately 7,500 new cases of EHCs were diagnosed in the United States in 2005 4, 5. A gradual improvement in the 5-year survival rates has occurred for patients with EHCs but the prognosis remains poor, with a 5-year survival rate of 12.5–40% 3, 5, 6, 7, 8, 9, 10, 11.

Surgical resection is the only curative treatment for EHC; however, most patients have unresectable disease or have positive surgical margins after resection 3, 6, 12, 13, 14. It has been suggested that RT may be of benefit in patients with EHCs in both the adjuvant and palliative setting; however, this remains controversial 15, 16, 17, 18, 19. Because of the low incidence of EHC, large randomized trials evaluating the effectiveness of RT in the postoperative and palliative settings are unavailable. The present study was designed to examine the role of RT in the postoperative and palliative setting in a large group of patients from the Surveillance, Epidemiology, and End Results (SEER) database.

Section snippets

Patient selection and treatment

The SEER database of the National Cancer Institute is a national cancer registry that collects information about the incidence and survival of cancer cases from 13 cancer registries. It includes approximately 26% of the U.S. population and is representative of national demographics. The SEER database was queried for the diagnosis of cholangiocarcinoma between 1988 and 2003. The “International Classification of Diseases for Oncology” (ICD-0-2 [1972–2000] and ICD-0-3 [2000–2002]) codes were used

Baseline patient characteristics

A total of 7,640 patients with EHC were identified for the period between 1973 and 2003. After eliminating all patients diagnosed before 1988, a total of 5,345 patients were available for analysis. RT details were lacking for 168 patients who were excluded from the analysis. Finally, after eliminating patients without surgical information, a total of 4,758 patients were available for analysis.

The patient demographics are listed by treatment category in Table 1; 52.5% of the patients were white

Discussion

Patients with EHC, treated with palliative RT, had a significant improvement in OS compared with patients treated with no RT or surgery on both multivariate and propensity score analyses. The results demonstrated a 5-month improvement in median OS and a 44% reduction in the risk of death. Surgery plus RT was associated with a 7-month improvement in median OS and a 5% reduction in the risk of mortality compared with surgery alone. However, after adjusting for potential confounders using the

Conclusion

It is possible that with careful patient selection, such as selecting those with positive margins, RT would be of benefit. To better define the role of RT in the adjuvant setting, additional prospective trials are needed. Given the locally aggressive nature of this disease, multimodality treatment should be investigated. Toxicity remains a problem; however, proton therapy might be a way to limit the dose to critical structures and allow both RT and concurrent chemotherapy doses to be increased

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    Funded, in part, by a grant from the Pennsylvania Department of Health.

    The Pennsylvania Department of Health specifically disclaims responsibility for any analysis, interpretations, or conclusions. Nandita Mitra was also funded by the Abramson Cancer Center of the University of Pennsylvania Core Support Grant, NIH grant P30-CA016520.

    Conflict of interest: none.

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