Treatment outcomes of patients with extremely advanced inoperable Hepatocellular Carcinoma (HCC) after yttrium-90 radioembolization

Abstract

Introduction: Inoperable hepatocellular carcinoma (HCC) confers a grave prognosis especially those exhibiting portal vein invasion. Radioembolization with yttrium-90 microspheres as selective internal radiation therapy demonstrated favorable outcomes for this intractable disease.We reported our series of patients with extremely advanced unresectable HCC treated with yttrium-90 micospheres. Methods: Patients with extremely advanced inoperable and evaluable HCC including those with single lesion >8cm in maximal diameter or multiple bi-lobar lesions (total >5 lesions) or portal vein invasion were evaluated by hepatic angiography and macroalbumin aggregate (MAA) scan for feasiblity for radioembolization. Dose of yttrium-90 was determined by Body Surface Area (BSA) method with an aim to achieve dose to tumour >200Gy, dose to normal liver <80Gy and lung shunting <10%.

Treatment outcomes including best local response rate, best local disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity were assessed. Univariate and multivariate analysis were also performed any prognostic factors for survival. Results: After pre-treatment hepatic angiography and MAA scan, 28 patients with a median age of 63.0 years (range 36-84) were considered feasible for SIRT. All patients have evaluable lesions for response assessment. Prior treatment before radioembolization was performed in 17 patients (60.7%), including 14 patients (50.0%) who had received transarterial chemoembolization (TACE) before. Mean alpha-feto protein (AFP was 19.5 ng/ml (range 1.0 to 10389.0 ng/ml). Median radioactivity of yttrium-90 prescribed was 1.48 GBq (range 0.85 to 2.30 GBq). After a median follow up of 16.2 months, the best local response rate was 21.4% and the best local disease control rate was 39.3%. Median overall PFS and OS were 3.25 months and 11.5 months respectively. Longer median PFS was noted in those who had prior TACE before radioembolization (7.3 vs. 3.1 months, p = 0.035), duration of AFP response >6 months (11.8 vs. 3.1 months, p = 0.020) and whose tumour had absence of portal vein invasion (4.5 vs. 3.1 months, p = 0.057). Longer median OS were also revealed in those without portal vein invasion (17.1 vs. 4.4 months, p = 0.020) and those whose duration of AFP response >6 months (19.8 vs. 8.2 months, p = 0.008). Four patients (14.3%) developed grade 3 or above toxicity including 1 patient who had persistent radiation peptic ulcer requiring gastrectomy. Univariate analysis showed that prior TACE (p = 0.043) and duration of AFP response >6 months were prognostic of PFS, whereas absence of portal vein invasion (p = 0.027) and duration of AFP response >6 months (p = 0.017) were prognostic factors of OS. Multivariate analysis revealed that prior TACE (p = 0.041) and duration of AFP response >6 months (p = 0.001) were prognostic of both PFS while absence of portal vein invasion (p = 0.050) and duration of AFP response >6 months (p = 0.005) were prognostic of OS. Conclusion: Ytrrium-90 radioembolization was able to produce promising treatment outcomes even in extremely advanced HCC. Absence of portal vein invasion and long AFP response were favorable prognostic factors for OS.