Efficacy and safety of image-guided hypofractionated radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective, multicenter study

Abstract

Background: External beam radiation therapy (RT) has shown promising effects for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) in recent studies. However, there is still a lack of consensus on the optimal RT scheme for PVTT treatment. We evaluated the efficacy and safety of image-guided 10-fraction hypofractionated RT in these patients.

Methods: Between January 2016 and March 2022, a total of 95 HCC patients with PVTT received 10-fraction hypofractionated image-guided radiation therapy (IGRT) at two institutes, and 69 patients were analyzed. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein, and Vp4 = main portal vein. Response evaluation was performed using Response Evaluation Criteria in Solid Tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT.

Results: The median prescribed dose of 50 Gy (range: 40-50 Gy; biologically effective dose [BED]: 56-75Gy₁₀) was delivered in 10 fractions. In this cohort, 4.3% of patients had Vp1, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. Median Planning target volume was 105.3 cc (interquartile range [IQR], 74.1-179.4 cc). Fifty-two (75.4%) patients received 50 Gy. With a median follow-up of 10.2 months (IQR, 6-21 months), the median OS was 20.3 months, and 1-year FFLP, PFS, and OS rates were 88.7%, 26.9%, and 62.2%, respectively. At 3 months follow-up, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, alpha-fetoprotein level ≥ 600 IU/ml (hazard ratio [HR] 2.06, p = 0.03), Child-Pugh Class B or C (HR 2.30, p = 0.02), and stage IVA or IVB (4.05, p = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.9%) cases of grade ≥ 3 toxicity: grade 3 liver enzyme elevation (n = 1), and acute cholangitis (n = 1).

Conclusions: Hypofractionated RT demonstrated promising local PVTT control and OS rates with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED: 56-75 Gy₁₀) is a feasible treatment option for PVTT in HCC patients.

Keywords: Hepatocellular carcinoma; Hypofractionated radiation therapy; Image-guided radiation therapy; Portal vein tumor thrombosis.

Fig. 1

CONSORT diagram of retrospective cohort. fx, fraction; RT, radiation therapy; HCC, hepatocellular carcinoma; PVTT, portal vein tumor thrombosis

Fig. 2

Cumulative local recurrence rate (a), Progression fee survival (b) and Distant metastasis free survival (c), respectively

Fig. 3

Kaplan–Meier curve of overall survival

Fig. 4

Patients were divided in 2 groups according to the number of risk factors. The Kaplan–Meier curve of OS between two groups are shown. Risk factors are mUICC stage (IVA or IVB), AFP ≥ 600 IU/ml and Child–Pugh Class B or C. Low risk group = 0–1 risk factors. High risk group = 2–3 risk factors. OS, overall survival; mUICC stage, modified Union for International Cancer Control stage; AFP, Alpha-Fetoprotein