Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma

Purpose

Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients.

Methods and Materials

This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS).

Results

Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22–102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9–13), 6 (95% CI, 5–6), 7 (95% CI, 6–8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34–0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44–0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59–0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70–0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58–0.76)).

Conclusions

The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC.

Introduction

Cholangiocarcinomas are rare malignancies that comprise approximately 3% of all gastrointestinal cancers (1). The incidence and mortality from intrahepatic cholangiocarcinomas (IHC) has been rising, and the only curative treatment is surgery 2, 3. However, patients are commonly unable to undergo resection at presentation because the majority have advanced disease 1, 4. Although improved surgical techniques have increased resectability rates; approximately half of patients are still unresectable at the time of diagnosis 5, 6. Even in patients who are able to undergo surgical resection, positive resection margins are common, with frequent local recurrence 6, 7. The present study examines whether the addition of radiation therapy is associated with improved outcomes in IHC.

Prior studies have suggested that adjuvant radiation therapy may improve survival in patients with microscopically positive margins, although this remains controversial (8, 9, 10, 11, 12). Because approximately 50% of patients with IHC will present with unresectable disease, defining optimal treatments for these patients is imperative 5, 6. Studies have demonstrated that definitive radiation can improve pain and prolong patency of bile ducts in patients with unresectable disease 13, 14. However, whether radiation will improve survival in patients who cannot undergo resection is still debated (15).

Because of the low incidence of IHC, large randomized trials evaluating the effectiveness of radiation in both the post-surgical and definitive setting are unavailable. The present study was designed to examine the role of radiation in the postoperative and definitive setting in a large group of patients from the Surveillance, Epidemiology, and End Results (SEER) database.