Clinical Outcomes of Image-Guided Proton Therapy for Recurrent Hepatocellular Carcinoma after TACE and/or RFA Treatment

Abstract

<h3>Purpose/Objective(s)</h3> Additional treatment options for recurrent hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) and/or radiofrequency ablation (RFA) treatment are limited. Although proton therapy provides a more focused dose distribution on the tumor compared with X-ray therapy, the efficacy and safety of proton therapy for recurrent HCC remains unclear. The aim of this study was to evaluate the efficacy and safety of image-guided proton therapy (IGPT) for recurrent HCC after TACE and/or RFA. <h3>Materials/Methods</h3> Eligibility criteria were as follows: (1) histologically-confirmed or image-diagnosed recurrent HCC after TACE and/or RFA treatment; (2) intrahepatic recurrence cases other than treatment site recurrence are not included (3) no previous radiotherapy around the lesion and other HCC; (4) age > 20 and ≤ 80 years; (5) ECOG-PS ≤ 2; (6) Child-Pugh classification A5-B9; (7) dose constraints of the organs at risk achievable; (8) no portal vein or inferior vena cava tumor thrombus; and (9) written informed consent. Overall survival (OS), local control (LC), and progression-free survival rates were estimated using the Kaplan-Meier method. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 5.0. Quality of life (QOL) scores were evaluated with EORTC QLQ-C30 version 3.0, QLQ-HCC18, and SF-36. Prior to treatment planning, the fiducial marker was placed just adjacent to a recurrent tumor. IGPT was performed under respiratory gating. <h3>Results</h3> From June 2013 to December 2020, 80 patients were enrolled. Major underlying liver diseases were hepatitis B (n=19), hepatitis C (n=35), alcoholic hepatitis (n=9), and nonalcoholic fatty liver disease (n=17). The Child-Pugh score was A5 in 49 patients, A6 in 16, and B7-9 in 15. The number of Albumin-Bilirubin Grade 1, 2, and 3 were 40, 40, and 0, respectively. Nineteen patients had a history of hepatic resection for other HCC. Fifty-four patients with a peripherally-located tumor were given 66 GyE in 10 fractions and 26 with a central tumor received 72.6 GyE in 22 fractions. Maximum tumor diameter ranged from 10 to 174 mm (median, 31). The median follow-up period of surviving patients was 38.0 months (range: 12.0-96.0). The 3-year OS, LC and PFS were 81% (95% confidence interval: 71-90%), 92% (86-100%), and 38% (26-49%) respectively. In univariate analysis, Child classification, operability, and tumor diameter were associated with better survival, while only Child classification was associated in multivariate analysis. Clinical remission or sustained viral response were significant factors for OS in patients with HCC recurrence derived from hepatitis virus. Non-classic radiation-induced liver disease was observed in only 1 patient with decrease of Child-Pugh score (≥ 2 points). The QOL score did not change after 1 year. <h3>Conclusion</h3> IGPT is safe and effective for recurrent HCC after TACE and/or RFA treatment. IGPT may become one of standard treatments as a curative treatment for recurrent HCC.