Effect of ablative radiotherapy on survival in patients with inoperable intrahepatic cholangiocarcinoma: A dose response analysis.

Abstract

294 Background: Advances in radiotherapy (RT) techniques and image guidance (IGRT) have enabled ablative doses to be delivered to large liver tumors. We evaluated the effects of RT dose escalation in the treatment of intrahepatic cholangiocarcinoma (IHCC). Methods: 79 consecutive patients with inoperable IHCC were treated between 2002–2014. Median tumor size 7.9 cm (range 2.2–17 cm), 57% had nodes+ and 20% had metastatic disease. 89% received gemcitabine and cisplatin before RT (35–100 Gy, median 58.05 Gy) for a median biologic equivalent dose (BED) of 80.5 Gy (range 43.75–180 Gy). 57% were treated with concurrent capecitabine. CT on rails IGRT with gating were used to deliver higher doses. Results: Median FU was 33 months (range 11–93 ). Median overall survival rate (OS) after diagnosis was 30 months; 1, 2, and 3-year OS rates were 87%, 61%, 44%. The median duration of local tumor control (LC) was 23 months; 1, 2, and 3-year LC rates were 81%, 45% and 27%. RT dose was the most important prognostic factor. Higher doses correlated with improved LC and OS. The 3-year OS for a BED greater than 80.5 was 73% versus 38% for those receiving lower doses (P =0.017). Similarly, 3-year LC was significantly higher (78% versus 45%, P= 0.04). On multivariate analysis, RT dose was significant for LC (P= 0.004) and OS (P= 0.006). The majority of patients (32/36, 89%) whose cause of death could be determined died from liver failure related to intrahepatic disease progression. Only 4 patients (11%) died from distant metastatic disease. There were no significant treatment related toxicities. Conclusions: Higher doses of RT improve LC and OS in inoperable IHCC. A BED > 80.5 Gy appears to be ablative for large IHCCs. Long term survival rates compare favorably to resection. RT schedules that achieve a BED > 80.5, such as 67.5 Gy in 15 fractions and 75 Gy in 25 fractions, should be used. Solutions for internal organ motion and IGRT are necessary for safe delivery of high doses near bowel. These findings support the use of 67.5 Gy in 15 fractions (BED = 97.88 Gy) in the current phase III NRG-GI001 randomized trial evaluating whether the addition of RT to chemotherapy affects survival for inoperable IHCC patients.