Proton beam therapy outcomes for localized unresectable hepatocellular carcinoma

• Published in: Radiotherapy and oncology Vol. 133; pp. 54 - 61
• Main Authors: Chadha, Awalpreet S., Gunther, Jillian R., Hsieh, Cheng-En, Aliru, Maureen, Mahadevan, Lakshmi S., Venkatesulu, Bhanu P., Crane, Christopher H., Das, Prajnan, Herman, Joseph M., Koay, Eugene J., Taniguchi, Cullen, Holliday, Emma B., Minsky, Bruce D., Suh, Yelin, Park, Peter, Sawakuchi, Gabriel, Beddar, Sam, Odisio, Bruno C., Gupta, Sanjay, Loyer, Evelyne, Kaur, Harmeet, Raghav, Kanwal, Javle, Milind M., Kaseb, Ahmed O., Krishnan, Sunil
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.04.2019
• Subjects: Aged; Aged, 80 and over; Carcinoma, Hepatocellular - diagnostic imaging; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - radiotherapy; Disease Progression; Dose escalation; Dose-Response Relationship, Radiation; Female; Four-Dimensional Computed Tomography - methods; Humans; Kaplan-Meier Estimate; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - pathology; Liver Neoplasms - radiotherapy; Male; Middle Aged; Primary liver cancer; Proton radiation; Proton Therapy - methods; Radiotherapy Planning, Computer-Assisted; Survival Rate; Treatment Outcome; Dose escalation; Proton radiation; Primary liver cancer
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2018.10.041

•Escalating radiation dose to hepatocellular carcinoma (HCC) using protons is feasible.•Moderate-to-large unresectable tumors in a Western cohort of patients.•Median overall survival is 30.7 months; actuarial 2-year local control is 82%.•Biologically effective dose > 90 GyE results in improved overall survival.•Toxicity was minimal. This study documents the utilization and efficacy of proton beam therapy (PBT) in western patients with localized unresectable hepatocellular carcinoma (HCC). Forty-six patients with HCC, Child-Pugh class of A or B, no prior radiotherapy history, and ECOG performance status 0–2 received PBT at our institution from 2007 to 2016. Radiographic control within the PBT field (local control, LC) and overall survival (OS) were calculated from the start of PBT. Most (83%) patients had Child-Pugh class A. Median tumor size was 6 cm (range, 1.5–21.0 cm); 22% of patients had multiple tumors and 28% had tumor vascular thrombosis. Twenty-five (54%) patients received prior treatment. Median biologically effective dose (BED) was 97.7 GyE (range, 33.6–144 GyE) administered in 15 fractions. Actuarial 2-year LC and OS rates were 81% and 62% respectively; median OS was 30.7 months. Out-of-field intrahepatic failure was the most common site of disease progression. Patients receiving BED ≥90 GyE had a significantly better OS than those receiving BED <90 GyE (49.9 vs. 15.8 months, p = 0.037). A trend toward 2-year LC improvement was observed in patients receiving BED ≥90 GyE compared with those receiving BED <90 GyE (92% vs. 63%, p = 0.096). On multivariate analysis, higher BED (p = 0.023; hazard ratio = 0.308) significantly predicted improved OS. Six (13%) patients experienced acute grade 3 toxicity. High-dose PBT is associated with high rates of LC and OS for unresectable HCC. Dose escalation may further improve outcomes.