Is adjuvant radiotherapy needed after curative resection of extrahepatic biliary tract cancers? A systematic review with a meta-analysis of observational studies.

BACKGROUND: The role for adjuvant radiotherapy (ART) after curative resection in extrahepatic cholangiocarcinoma remains unclear. Due to the lack of randomized trials, available data comes from single center experiences or data-based population studies with inconclusive results. OBJECTIVE: To assess the impact of radiotherapy (with or without concurrent chemotherapy) on toxicity and survival of radically resected patients with extrahepatic bile duct cancer (extrahepatic cholangiocarcinoma, gallbladder cancer and pure ampullary cancer). DATA SOURCES AND STUDY SELECTION: Eligible studies with data on survival, recurrence and toxicity were retrieved from the MEDLINE, ISI web of science, EMBASE and Cochrane databases from January 1995 to December 2008, to ensure that all ART treatments were performed with conventional 3D techniques. In the absence of randomized controlled-studies, all observational cohort studies (longitudinal and historical) were initially considered. Ten retrospective cohort studies (where the use of concurrent CT was reported only in 2), met all inclusion criteria and were enrolled for final meta-analysis. Hazard ratio (HR) had to be extracted from survival curves using the Tierney et al. methods. MIX 1.7 statistical software was used for meta-analysis. RESULTS: All studies on ART used conventional 3D-techniques. Patients in the ART cohorts were more likely to have involved surgical margins and positive lymph nodes. For extrahepatic cholangiocarcinoma location, ART significantly improved overall survival (HR 0.62; 95% CI 0.48 to 0.78, p<0.001). Meta-analysis was not feasible for gallbladder cancer and ampullary cancer locations. Late radiation-induced toxicity was low (2-9% late obstruction or GI bleeding). CONCLUSION: In the absence of randomized controlled studies, we found in the present systematic review and meta-analysis of observational studies that, patients with extrahepatic cholangiocarcinoma treated with adjuvant RT have a significant lower risk of dying compared to patients treated with surgery alone.

Adjuvant radio-chemotherapy for extrahepatic biliary tract cancers.

BACKGROUND: Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. METHODS: Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.4 Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%). Surgical margins were negative in 11 patients (48%), narrow in 2 (9%), and microscopically involved in 8 (35%). Eleven patients (55%) had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98). RESULTS: Acute gastrointestinal grade 2 toxicity (RTOG scale) was recorded in 2 patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) and 2 patients (9%) respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung). No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p=0.04). The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p=0.07). CONCLUSIONS: Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor location.