Clinical benefit of radiation therapy and metallic stenting for unresectable hilar cholangiocarcinoma.
OBJECTIVE
To determine the efficacy of external beam radiotherapy (EBRT), with or without intraluminal brachytherapy (ILBT), in patients with non-resected locally advanced hilar cholangiocarcinoma.


METHODS
We analyzed 64 patients with locally advanced hilar cholangiocarcinoma, including 25 who underwent resection (17 curative and 8 non-curative), 28 treated with radiotherapy, and 11 who received best supportive care (BSC). The radiotherapy group received EBRT (50 Gy, 30 fractions), with 11 receiving an additional 24 Gy (4 fractions) ILBT by iridium-192 with remote after loading. ILBT was performed using percutaneous transhepatic biliary drainage (PTBD) route. Uncovered metallic stents (UMS) were inserted into non-resected patients with obstructive jaundice, with the exception of four patients who received percutaneous transhepatic biliary drainage only. UMS were placed endoscopically or percutaneously, depending on the initial drainage procedure. The primary endpoints were patient death or stent occlusion. Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups. Stent patency was compared in the radiotherapy and BSC groups.


RESULTS
No statistically significant differences in patient characteristics were found among the resection, radiotherapy, and BSC groups. Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone; cholangitis occurred after endoscopic stenting, and patients were treated with PTBD. A total of 16 patients were administered additional systemic chemotherapy (5-fluorouracil-based regimen in 9, S-1 in 6, and gemcitabine in 1). Overall survival varied significantly among groups, with median survival times of 48.7 mo in the surgery group, 22.1 mo in the radiotherapy group, and 5.7 mo in the BSC group. Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery (P = 0.0076). Cumulative survival in the radiotherapy group was significantly longer than in the BSC group (P = 0.0031), but did not differ significantly from those in the non-resection group. Furthermore, the median survival time of patients in the radiotherapy group who were considered for possible resection (excluding the seven patients who were not candidates for surgery due to comorbid disease or age) was 25.9 mo. Stent patency was evaluated only in the 24 patients who received a metallic stent. Stent patency was significantly longer in the radiotherapy than in the BSC group (P = 0.0165). Biliary drainage was not eliminated in any patient. To determine the efficacy of ILBT, we compared survival time and stent patency in the EBRT alone and EBRT plus ILBT groups. However, we found no significant difference in survival time between groups or for stent patencies. Hemorrhagic gastroduodenal ulcers were observed in 5 patients (17.9%), three in the EBRT plus ILBT group and two in the EBRT alone group. Ulcers occurred 5 mo, 7 mo, 8 mo, 16 mo, and 29 mo following radiotherapy. All patients required hospitalization, but blood transfusions were unnecessary. All 5 patients recovered following the administration of anti-ulcer medication.


CONCLUSIONS
Radiotherapy improved patient prognosis and the patency of uncovered metallic stents in patients with locally advanced hilar cholangiocarcinoma, but ILBT provided no additional benefits.
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. isayama-tky@umin.ac.jp
Hiroyuki
H
Isayama
Takeshi
T
Tsujino
Yousuke
Y
Nakai
Takashi
T
Sasaki
Keiichi
K
Nakagawa
Hideomi
H
Yamashita
Taku
T
Aoki
Kazuhiko
K
Koike
D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D001653:Bile Ducts, Intrahepatic / Q000601:surgery*; D001662:Biliary Tract Surgical Procedures; D001918:Brachytherapy / Q000379:methods*; D018281:Cholangiocarcinoma / Q000532:radiotherapy* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007496:Iridium Radioisotopes / Q000627:therapeutic use*; D041781:Jaundice, Obstructive / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010166:Palliative Care / Q000379:methods*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D011878:Radiotherapy / Q000379:methods*; D015607:Stents; D016896:Treatment Outcome
D007496:Iridium Radioisotopes; D019275:Radiopharmaceuticals