Outcomes of Hepatocellular Carcinoma Treated with TACE Followed By Liver SBRT

Abstract

We evaluated toxicity and factors associated with local recurrence, overall survival (OS) and disease-free survival (DFS) in patients with hepatocellular carcinoma (HCC) who received trans-arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT). We identified 60 patients with HCC who received TACE and SBRT at our institution between 2007 and 2015. SBRT was administered as 14 – 54 Gy in 1-5 fx. Child-Turcotte-Pugh (CTP) status, indication for SBRT (consolidation or recurrent disease), number of liver lesions receiving SBRT, and number of TACE times prior to SBRT were recorded. Cross-sectional imaging (MRI and/or CT) were reviewed for lesion size. We recorded maximum lesion diameter (additive when multiple lesions present) as a measure of tumor burden. Toxicity was based on CTCAE version 4.03. Local recurrence was evaluated on follow-up cross-sectional imaging using RECIST criteria (version 1.1), and was available for 57 patients. Kaplan-Meier analyses with log-rank tests were performed to evaluate OS and DFS. We performed an ROC analysis to identify tumor size cutoff. Median OS was 21.6 months and median DFS was 13.4 months. Three patients recurred locally for a LR rate of 5%. 14 patients (24.6%) recurred with new liver lesions and two patients (3.5%) developed metastatic disease. The OS and DFS were increased among CTP A patients in comparison to CTP B patients (OS: 27.7months vs 9.5months, p=0.006, DSF: 15.4months vs 8.4months, p=0.024). For tumor burden, a cutoff value was identified at 2.05 cm. Tumor burden < 2.05 cm resulted in higher OS and DSS (OS: 53.6months vs 15.4months, p=0.003; DFS: 53.6 months vs 11.1months, p=0.006). Providing SBRT to multiple liver lesions correlated with decreased OS and DFS (OS: 10.0months vs 27.7months, p=0.017, DFS 6.6months vs 15.7months, p=0.04). Indication for SBRT (consolidation or recurrent disease) and receiving TACE multiple times prior to SBRT were not associated with differences in OS or DFS. Observed toxicities during and/or after SBRT include: nausea (31.7% of patients, grade 1), abdominal pain (15%, grade 1-2), chest wall pain/rib fractures (5% of patients, grade 1-3), diarrhea (3.5%, grade 1) and skin erythema (1.7%, grade 1). One patient died due to a gastric ulcer attributed to radiation therapy. No patients developed classical radiation-induced liver disease (RILD) although 3 patients (5%) developed non-classical RILD. Liver SBRT after TACE for HCC results in excellent local control and has a favorable side effect profile. CTP class A, tumor burden <2.05, and having a single lesion treated with SBRT are associated with increased OS and DFS in this patient population.