A Prospective Study of the Safety and Efficacy of Liver Stereotactic Body Radiation Therapy in Patients With Prior Liver-Directed Therapy

Abstract

To determine the toxicities and outcomes after stereotactic body radiotherapy (SBRT) for patients with hepatocellular carcinoma (HCC) and metastatic disease to the liver who had prior liver-directed therapy. Patients with ECOG 0-1, Child-Pugh Class A or B, and primary liver cancer or liver metastases (≤ 3) unsuitable for surgical resection or radiofrequency ablation (RFA) were eligible. SBRT dose goal was 45 Gy in 3 fractions, but was modified based on estimated liver tolerance by a predetermined dose de-escalation scheme. Treatments were delivered with a CyberKnife system that used tracking of liver motion with implanted fiducials. Toxicities were graded by the CTCAE v.3.0 criteria. Local progression was defined as an increase by ≥ 50% in the product of the two perpendicular diameters of a previously irradiated lesion. A total of 30 patients were enrolled from 6/2009 to 3/2014 at two institutions. Eleven patients (37%) had primary HCC and 19 (63%) patients had liver metastases. Almost half of the patients in this cohort (47%) had prior liver-directed therapies including 30% with liver resection, 20% with RFA, and 23% with trans-arterial chemoembolization (TACE). Among the 9 patients with prior liver surgery, 7 underwent resection of ≥ 2 segments, 4 of whom had a hepatic lobectomy. The median dose of SBRT delivered was 45 Gy in 3 fractions (range 27.5-45 Gy) to a median GTV diameter of 3.5 cm (range 1.7-6.5 cm). At a median follow-up of 12.7 months, 1-year local control was 80% in the entire cohort, 82% among those with HCC, and 79% among those with liver metastases. Cumulative grade 2 and grade 3 acute toxicity (≤ 90 days) possibly attributable to SBRT occurred in 47% and 7% of patients, respectively. The two grade 3 toxicities observed were elevated AST and leukopenia. There were no acute grade 4 or 5 toxicities. Four patients (13%) experienced late grade 2 toxicities with no observed grade 3-5 late toxicity. Similar rates of grade 2 or greater acute toxicity rates were observed between patients who had prior liver-directed treatments and those who did not (43% vs 50%, respectively). Liver SBRT is a safe treatment for patients even in the setting of prior liver-directed surgical and ablative therapies as long as standard liver constraints are respected. Preliminary efficacy data suggests good local control of lesions in both primary HCC and liver metastasis settings.