Ablative radiation therapy for hepatocellular carcinoma is associated with reduced treatment- and tumor-related liver failure and improved survival

Abstract

Background: More than 70% of patients with hepatocellular carcinoma (HCC) are not candidates for curative therapy or recur after curative-intent therapy. There is growing evidence on the use of ablative radiation therapy (RT) for liver tumors. We aimed to analyze outcomes of HCC patients treated with conventional versus ablative RT. Methods:We retrospectively analyzed medical records of HCC patients treated with liver RT from 2001 to 2019. We defined ablative RT as biologically effective dose (BED) ≥80 Gy. RECIST 1.1 was used to define early responses at 3-6 months after RT, and local control (LC) at last follow-up (FU). Data was analyzed using Fisher exact test, Kaplan-Meier, cumulative incidence rates, Cox proportional hazards model and Fine-Gray competing risks.Results: Forty-five patients were identified, of whom 14 (31.1%) received ablative RT using a stereotactic technique. With median FU of survivors of 10.1 months, 1-year cumulative incidence of LC was 91.7% for ablative and 75.2% for BED <80 Gy. At early FU, patients treated with ablative RT had better responses compared to BED <80 Gy, with 7% progressing versus 19%, and 21.4% with complete response versus none (P=0.038). On univariate analysis (UVA), Child-Pugh (CP) score [hazard ratio (HR): 3 for CP-B, HR: 16 for CP-C] and BED (HR: 7.69 for BED <80 Gy) correlated with deterioration of liver function, leading to liver failure. Most liver failure cases were due to disease progression. No RT-related liver failure occurred in the ablative RT group. On UVA, only BED ≥80 Gy was associated with improved overall survival (OS) (HR: 0.4; P=0.044). Median OS (mOS) and 1-year OS were 7 months and 35% respectively for BED <80 Gy compared to 28 months and 66% for BED ≥80 Gy. No grade 3+ bowel toxicity was reported in either group.Conclusions: Greater than 90% LC was achieved after stereotactic ablative RT, which was associated with minimized tumor and treatment related liver failure and improved survival for highly selected inoperable HCC patients.

Proton Beam Therapy and Photon-Based Magnetic Resonance Image-Guided Radiation Therapy: The Next Frontiers of Radiation Therapy for Hepatocellular Carcinoma

“… 2 , 3 More recently, image-guided RT using computed tomography (CT) and magnetic resonance imaging (MRI), improved motion management, and highly conformal techniques such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) have made definitive irradiation of HCC more feasible. 2 , 4 , 5 CT-guided RT may either be accomplished with cone beam computed tomography (CBCT) or CT-on-rails. 6 , 7 On-board CT or MRI improves daily treatment position by allowing one to visualize the patient's liver contour near the tumor target volume.…”

Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma

“…Recent results from the RTOG-1112 trial at the ASTRO 2022 meeting also demonstrated improved OS, PFS and TTP when combining SBRT followed by sorafenib vs. sorafenib alone. Promising findings on ablative radiation therapy could mean significantly improved outcomes for patients with unresectable HCC [ 73 , 74 , 75 ]. Currently, several ongoing clinical trials intend to assess the outcomes of combining systemic therapy with radiation therapy (e.g., NCT04857684, NCT04913480, NCT04167293, NCT05286320).…”

“…The advantages of SBRT over IMRT are its ability to deliver higher radiation doses per treatment and its shorter overall treatment time [ 72 ]. Radiation treatment with either SBRT or fractionated RT can be ablative at a higher biologically effective dose (BED) (≥80 Gy), and was shown to improve hepatic tumor control, and possibly improve overall survival by preventing liver failure originating from tumor progression, when compared with the delivery of a lower BED in HCC patients ineligible for curative therapies ( Table 3 ) [ 73 ]. In patients with intrahepatic cholangiocarcinoma (ICC), a higher BED (>80.5 Gy), when compared to lower doses, was associated with significantly better 3-year OS (73% vs. 38%, respectively; p = 0.17) and 3-year LC (78% vs. 45%, respectively; p = 0.04; Table 3 ) [ 74 ].…”

Proton Therapy in the Management of Hepatocellular Carcinoma

“…Local control of HCC in the liver is crucial to slow or prevent disease progression, and subsequent progression to liver failure. Although modern series of photon stereotactic ablative RT have shown excellent local control outcomes in the treatment of HCC [ 95 ], protons have dosimetric advantages, especially in certain clinical scenarios. There is a growing body of evidence supporting the use of proton therapy for HCC [ 26 , 46 , 47 , 55 , 57 , 58 , 67 ].…”