External-beam radiotherapy for localized extrahepatic cholangiocarcinoma

The role of radiation therapy (RT) in extrahepatic cholangiocarcinoma (EHCC) is not clear and only limited reports exist on the use of this modality. We have reviewed our institutional experience to determine the pattern of failure in patients after potentially curative resection and the expected outcomes after adjuvant RT and in unresectable patients.

After institutional review board approval, 81 patients diagnosed with EHCC (gallbladder 28, distal bile duct 24, hilar 29) between June 1986 and December 2004 were identified and their records reviewed. Twenty-eight patients (35%) underwent potentially curative resection with R0/R1 margins. Fifty-two patients (64%) were unresectable or underwent resection with macroscopic residual disease (R2). All patients received three-dimensional planned megavoltage RT. The dose for each patient was converted to the equivalent total dose in a 2 Gy/fraction, using the linear-quadratic formalism and alpha/beta ratio of 10. The median dose delivered was 58.4 Gy (range, 23-88.2 Gy). 54% received concomitant chemotherapy.

With a median follow-up time of 1.2 years (range, 0.1-9.8 years) 75 patients (93%) have died. Median overall survival (OS) and progression-free survival (PFS) were 14.7 (95% CI, 13.1-16.3) and 11 (95% CI, 7.6-13.2) months, respectively. There was no difference among the three disease sites in OS (p = 0.70) or PFS (p = 0.80). Complete resection (R0) was the only predictive factor significantly associated with increase in both OS and PFS (p = 0.002), and there was no difference in outcomes between R1 and R2 resections. The first site of failure was predominantly locoregional (68.8% of all failures).

Local failure is a major problem in EHCC, suggesting the need for more intense radiation schedules and better radiosensitizing strategies. Because R1 resection appears to convey no benefit, it appears that surgery should be contemplated only when an R0 resection is likely. Borderline-resectable patients might be better served by neoadjuvant therapy.