Attila Nakeeb1, Henry A Pitt. 1. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract
BACKGROUND: Hilar cholangiocarcinoma is a rare tumour which is best managed by an aggressive surgical approach. The role of adjuvant or neoadjuvant radiation therapy, chemotherapy or chemoradiation remains controversial, as no prospective randomized studies have been performed. METHODS: This review summarizes the recent literature regarding the role of radiation, chemotherapy and chemoradiation in hilar cholangiocarcinoma. The results of a biliary cancer questionnaire regarding current treatment strategies are also reported. RESULTS: A number of retrospective studies have shown that patients treated with adjuvant radiation therapy have prolonged survival compared with untreated patients. However, most of these reports did not control for tumour stage or performance status. A carefully controlled trial from the Johns Hopkins Hospital did not demonstrate any benefit for adjuvant radiation therapy. A number of phase II trials of chemotherapy have demonstrated modest response rates (20-40%). The best responses have been reported with 5-fluorouracil (5-FU) in combination with interferon-alpha or with leucovorin and mitomycin C. Recent non-randomized reports of chemoradiation with 5-FU with or without gemcitabine as the radiosensitizer suggest, but do not prove, improved survival. Adjuvant chemoradiation is currently being employed at specialized centres most often in the Americas (71%) and the Asia/Pacific region (55%) and to a lesser degree in Europe (29%). DISCUSSION: The only chance for long-term survival in patients with hilar cholangiocarcinoma is complete resection with negative margins. Neither radiation therapy nor chemotherapy alone has been proven to prolong survival in completely or partially resected patients or in unresected patients. Recent uncontrolled data suggest that chemoradiation may improve survival in resected and locally unresectable patients. However, prospective, randomized multicentre trials need to be performed to confirm efficacy.
BACKGROUND:Hilar cholangiocarcinoma is a rare tumour which is best managed by an aggressive surgical approach. The role of adjuvant or neoadjuvant radiation therapy, chemotherapy or chemoradiation remains controversial, as no prospective randomized studies have been performed. METHODS: This review summarizes the recent literature regarding the role of radiation, chemotherapy and chemoradiation in hilar cholangiocarcinoma. The results of a biliary cancer questionnaire regarding current treatment strategies are also reported. RESULTS: A number of retrospective studies have shown that patients treated with adjuvant radiation therapy have prolonged survival compared with untreated patients. However, most of these reports did not control for tumour stage or performance status. A carefully controlled trial from the Johns Hopkins Hospital did not demonstrate any benefit for adjuvant radiation therapy. A number of phase II trials of chemotherapy have demonstrated modest response rates (20-40%). The best responses have been reported with 5-fluorouracil (5-FU) in combination with interferon-alpha or with leucovorin and mitomycin C. Recent non-randomized reports of chemoradiation with 5-FU with or without gemcitabine as the radiosensitizer suggest, but do not prove, improved survival. Adjuvant chemoradiation is currently being employed at specialized centres most often in the Americas (71%) and the Asia/Pacific region (55%) and to a lesser degree in Europe (29%). DISCUSSION: The only chance for long-term survival in patients with hilar cholangiocarcinoma is complete resection with negative margins. Neither radiation therapy nor chemotherapy alone has been proven to prolong survival in completely or partially resected patients or in unresected patients. Recent uncontrolled data suggest that chemoradiation may improve survival in resected and locally unresectable patients. However, prospective, randomized multicentre trials need to be performed to confirm efficacy.
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