Predictors of Failure and Survival in Patients with Hepatocellular Carcinoma Treated with Stereotactic Body Radiation Therapy

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Stereotactic body radiation therapy (SBRT) has been used as an effective treatment or as a bridge to liver transplant in patients with hepatocellular carcinoma (HCC). Despite high published rates of local control, failures can occur. In this study, we report our single institution experience and analyze treatment- and patient-related factors predicting for failure and overall survival. We performed a retrospective analysis of HCC patients treated with SBRT at our institution between 6/2007 and 1/2017. Biological effective dose (BED) was calculated using alpha/beta = 10. Failure was defined as in-field if happened within 80% isodose line, out-field if failure happened outside 80% isodose line but within the liver, and distant if failure occurred outside the liver. Absolute lymphocyte count (ALC) nadir was defined as the lowest ALC within 2 months after SBRT and the cut off used to define low ALC nadir was < 0.5 k cells/ul. Statistical analysis was done using chi-squared testing, logistic regression, and Kaplan -Meier methods. We identified 92 patients with a median age of 63 years (IQR 57-76 years); 71% were male; 72% had Child Pugh A and 64% had ECOG of 1. The most common cause of HCC was hepatitis C (56%) followed by non-alcoholic steatohepatitis(24%). The median tumor size was 26 mm (range 12-148 mm), with a median dose of 48 Gy (range 20-50 Gy) and median BED of 124.8 (range of 28-133). With median follow-up of 19.5 months, there were 21 (22.8%) patients with any failure: 5 (22%) were in-field, 13 (%64) were out-of-field, and 5 (%22) were distant metastases. Of note, 2 patients had concurrent in- and out-field failure. Progression free survival was 18 months (range 2-97 months). The mortality rate was 36% and 52% in patients who developed any type of failure. Univariate analysis revealed that pre-treatment alpha fetoprotein (AFP) is associated with risk of any failure (p=0.04). In addition, pre-treatment International Normalized Ratio (INR) is associated with risk of in-field failure (p=0.007). BED or dose were not associated with any failure (p=0.49, p=0.37). Patient with low ALC nadir had a lower overall survival (OS, 13 months versus 30 months, p-value=0.006) Baseline, 3-month and 1-year AFP were not associated with time to any failure (p=NS). In-field failure was associated with improved OS (p=0.03). Distant failure was associated with higher rate of mortality (p=0.004). We report our single institution experience of treating HCC patients with SBRT to define factors associated with failure and survival. The rate of any failure was 22.8% with low in-field failure (5.4%) after SBRT. The only factor associated with any failure was baseline AFP. Low ALC nadir was also associated with lower OS. These factors should be evaluated prospectively for validation.