Toxicity of Ablative Radiation Therapy in the Management of Patients with Child-Pugh B/C Liver Function and Unresectable Hepatocellular Carcinoma (HCC)

TL;DR

Ablative radiation therapy is safe and effective for patients with liver cancer and poor liver function, showing low liver toxicity and good tumor control.

Contribution

This study demonstrates that ablative radiation therapy is well tolerated in patients with Child-Pugh B/C liver function and unresectable HCC.

Findings

Only 10.3% of patients developed non-classical radiation-induced liver disease.

Local tumor control at 2 years was 73% in treated lesions.

Median overall survival was 12 months with low rates of severe hepatobiliary toxicity.

Abstract

Hepatocellular carcinoma (or primary liver cancer) remains a leading cause of cancer-related deaths, with incidence rates increasing in certain parts of the world. Treatment options outside of surgical resection or transplant remain poorly defined, particularly for those with decompensated underlying liver function, leaving few available treatment options. The role for ablative radiation therapy for these patients has been limited historically given understandable concern regarding the potential for radiation-induced liver dysfunction. Our series evaluating the use of ablative radiation therapy in those with decompensated liver function (primarily Child-Pugh B) demonstrated that treatment is well tolerated with low rates of radiation-induced liver dysfunction and encouraging rates of local tumor control.

Background/Objectives: Hypofractionated ablative radiation is an increasingly popular option for patients with hepatocellular carcinoma (HCC). However, concern remains about the risk for radiation-induced liver toxicity in patients with decompensated liver function. Methods: We retrospectively identified patients with underlying Child-Pugh (CP) B or C liver function treated at our University and Veterans Affairs (VA) departments from 2014 to 2019. Primary endpoints included treatment-related toxicity and dosimetric parameters. Results: 38 patients were included in the analysis. Most patients (98%) had CP B or Albumin-Bilirubin (ALBI) grade 2–3 (100%) liver disease. The median dose was 50 Gy (range 30–50) delivered in 5 or 10 fractions. Most patients had a single tumor treated (66%) with a median size of 3.1 cm (Interquartile Range (IQR) 2.3–4.1). The mean liver dose was 9.28 Gy (IQR 6.76–13.64) with a liver D800cc of 3.99 Gy (IQR 1.41–8.02). All patients completed their intended course with a median follow-up of 43 months. Four patients (10.3%) developed non-classical radiation-induced liver disease (RILD), comparable to the rate for patients with CP A function treated contemporaneously (8.3%). Otherwise, one patient (2.6%) experienced acute grade 3+ (non-RILD) hepatobiliary toxicity, while one patient (2.6%) experienced late grade 3+ hepatobiliary toxicity. Local control was promising with 2-year freedom from progression in the treated lesion of 73% (95% CI 38–91%). Median overall survival was 12 months (95% CI 5–25 months). Conclusions: Ablative radiation for patients with decompensated liver function and HCC appears well tolerated with low rates of RILD and encouraging local control. With careful selection, these patients should be considered for inclusion in future randomized trials.

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