Radiotherapy in the Treatment of Patients With Unresectable Extrahepatic Cholangiocarcinoma

Abstract

Purpose Extrahepatic cholangiocarcinoma is an uncommon but lethal malignancy. We analyzed the role of definitive chemoradiotherapy for patients with nonmetastatic, locally advanced extrahepatic cholangiocarcinoma treated at a single institution. Methods and Materials This retrospective analysis included 37 patients who underwent external beam radiation therapy (EBRT) with concurrent chemotherapy and/or brachytherapy (BT) for locally advanced extrahepatic cholangiocarcinoma. Local control (LC) and overall survival (OS) were assessed, and univariate regression analysis was used to evaluate the effects of patient- and treatment-related factors on clinical outcomes. Results Twenty-three patients received EBRT alone, 8 patients received EBRT plus BT, and 6 patients received BT alone (median follow-up of 14 months). Two patients were alive without evidence of recurrence at the time of analysis. Actuarial OS and LC rates at 1 year were 59% and 90%, respectively, and 22% and 71%, respectively, at 2 years. Two patients lived beyond 5 years without evidence of recurrence. On univariate analysis, EBRT with or without BT improved LC compared to BT alone (97% vs. 56% at 1 year; 75% vs. 56% at 2 years; p = 0.096). Patients who received EBRT alone vs. BT alone also had improved LC (96% vs. 56% at 1 year; 80% vs. 56% at 2 years; p = 0.113). Age, gender, tumor location (proximal vs. distal), histologic differentiation, EBRT dose (≤ or >50 Gy), EBRT planning method (two-dimensional vs. three-dimensional), and chemotherapy were not associated with patient outcomes. Conclusions Patients with locally advanced extrahepatic cholangiocarcinoma have poor survival. Long-term survival is rare. The majority of patients treated with EBRT had local control at the time of death, suggesting that symptoms due to the local tumor effect might be effectively controlled with radiation therapy, and EBRT is an important element of treatment. Novel treatment approaches are indicated in the therapy for this disease.

Chemotherapy for cholangiocarcinoma: An update

“…Although it is widely used and recommended in guidelines from medical oncologist expert groups, the survival benefit of any adjuvant strategy has never been proven in specifically designed randomized clinical trials. Most of the recommendations are primarily based on practice patterns at some institutions and on retrospective studies from single center experiences [7,8] . There are limited data from multiple retrospective series and small phase Ⅱ trials from single institutions, but most of these studies are not randomized and with heterogeneous patient populations often combine gallbladder cancers with pancreatic cancers with intrahepatic and extrahepatic cholangiocarcinomas.…”

A review of the clinical diagnosis and therapy of cholangiocarcinoma

“…In patients with advanced CCA that is unsuitable for curative resection, radiotherapy alone or in combination with other approaches such as chemotherapy and/or biliary decompression is an effective treatment option, prolonging survival and improving quality of life. [100][101][102][103][104] Patients with resectable ECC who had microscopically positive resection margins showed higher median disease-free survival rates (21 months versus 10 months, P ¼ 0.042) and decreased local failure (35.6% versus 61.7%, P ¼ 0.02) with postoperative adjuvant radiation than with resection alone; these outcomes were doubled compared with no adjuvant therapy in patients with a positive resection margin and lymph node metastasis. 105 In patients with resected ICC and concurrent lymph node metastases, postoperative adjuvant radiotherapy improved the median survival time compared with no radiotherapy (19.1 months versus 9.5 months, P ¼ 0.011).…”

Impact of adjuvant chemoradiation on survival in patients with resectable cholangiocarcinoma

“…13 The high rate of local recurrence following resection suggests the need for aggressive adjuvant therapy, though few studies have addressed this issue to date. A few retrospective series have shown benefits in both local control and improved overall survival when using radiation therapy (RT) for unresectable CC, [14][15][16][17][18] establishing its activity in this disease. Adjuvant chemotherapy (CT) and/or concurrent chemoradiation (CRT) for resected CC has also been associated with increased survival in pooled meta-analyses of historic international series, especially in those with involved lymph nodes or microscopic residual disease following resection.…”