Salvage Radiation for Oligometastatic Recurrent Cholangiocarcinoma

Abstract

Outcomes for recurrent cholangiocarcinoma (CCA) after surgical resection treated with chemotherapy alone are poor with few long-term survivors. Some recurrences, however, are limited and might benefit from aggressive local therapy in addition to systemic therapy. We analyzed patients with recurrent oligometastatic cholangiocarcinoma managed with ablative radiation. We performed a retrospective review of patients in a single institution that had upfront resection of cholangiocarcinoma and exhibited oligometastatic recurrence treated with radiotherapy. Baseline characteristics were obtained, and patients were analyzed for overall survival (OS), progression free survival (PFS), and local control (LC) after receiving radiation. Descriptive statistics were used to analyze patient characteristics. OS, PFS and LC were assessed using the Kaplan-Meier method and the Cox proportional hazards model. We identified 30 patients with oligometastatic CCA treated with radiation of which 25 had ≥ 1 month of follow imaging to assess response and were used for analysis. Median follow-up was 43 months (range, 17-118). 8 (32%) patients had recurrences at the resection margin, 11 (44%) patients had elsewhere within liver, 5 (20%) in regional lymph nodes, and one (4%) in the lung. Median time to recurrence after surgery was 16 months (range, 4-74). 19 (76%) patients received chemotherapy at recurrence. Intensity-Modulated Radiation Therapy (IMRT; 54.5 Gy median dose) was used in 12 (48%) patients and 13 (52%) had Stereotactic Body Radiation Therapy (SBRT; 48 Gy median dose). Concurrent chemotherapy was given for 8 of the IMRT patients. Median OS from diagnosis was 42.6 months (range, 17-118) and 22.6 months (range, 3-65) from the time ablative radiation was given. Median PFS after salvage radiation was 8.9 months (range, 2-40). LC was 67.5% at 1 year. On univariate analysis, poor prognostic factors for OS included non-white race (n = 14, HR, 3.9; 95% confidence interval, 0.99-15.8; P = 0.05), pre-primary resection CA19-9 ≥200 (5.8; 1.4 to 24.8; P = 0.02), and distal location of CCA (vs. intrahepatic, 14.6; 3.2-67.1; P<0.001). CA19-9 at diagnosis ≥ 200 (4.08; 1.01-16.5; P = 0.049) and distal CCA (12.47; 2.4-64.4; P = 0.003) were also poorly associated with PFS. SBRT, compared to IMRT, showed a trend towards a positive prognostic factor for OS and PFS (0.32; 0.1-1.05; P = 0.06). Use of chemotherapy prior to RT, use of concurrent chemotherapy, tumor characteristics at diagnosis such as TNM criteria, positive margins or perineural/lymphovascular invasion, site of recurrence, age or gender and time to recurrence after surgery were not associated with neither OS nor PFS. Salvage radiation for well selected recurrent oligometastatic cholangiocarcinoma is associated with favorable OS and PFS compared to historical controls. Further study of this rare population is warranted.