Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2015; 21(46): 13101-13112
Published online Dec 14, 2015. doi: 10.3748/wjg.v21.i46.13101
Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma
Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryutaro Nomura, Kengo Sato, Ichiro Suzuki, Ryo Nakata
Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryo Nakata, Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan
Ryutaro Nomura, Kengo Sato, Ichiro Suzuki, Cyberknife Center, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan
Author contributions: Kato H wrote the manuscript; Yoshida H, Taniguch H, Nomura R, Sato K, Suzuki I and Nakata R contributed to the manuscript discussion and reviewed the manuscript.
Institutional review board statement: The study was reviewed and approved by the institutional review board of the Japanese Red Cross Medical Center. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: The statistical code and dataset are available from the corresponding author at hiroyuki.kato.911@gmail.com. Consent for data sharing was not obtained but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hiroyuki Kato, MD, Department of Gastroenterology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan. hiroyuki.kato.911@gmail.com
Telephone: +81-3-34001311 Fax: +81-3-34091604
Received: May 30, 2015
Peer-review started: June 5, 2015
First decision: September 9, 2015
Revised: September 25, 2015
Accepted: October 23, 2015
Article in press: October 26, 2015
Published online: December 14, 2015
Processing time: 192 Days and 22.8 Hours
Abstract

AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC).

METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model.

RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral bleeding and another patient had an esophageal ulcer after treatment.

CONCLUSION: The Cyberknife can be safely administered to patients with advanced or terminal stage HCC. High AFP levels were associated with worse survival, but a higher radiation dose improved the survival.

Keywords: Hepatocellular carcinoma; Stereotactic body radiotherapy; Cyberknife; Neoplasm metastasis/therapy; Liver radiotherapy

Core tip: Due to an aging of hepatocellular carcinoma (HCC) patient population, a growing number of patients are ineligible for conventional therapy. The Cyberknife® system delivers stereotactic body radiation therapy (SBRT), which offers minimally invasive treatment with high doses of radiation. There has been an increase in the number of successful reports of using SBRT against liver-confined HCC. We found that the Cyberknife can safely be administered even in patients with advanced or terminal stage HCC. Our results suggest that SBRT may have the potential to increase the overall survival for advanced stage HCC patients. High alpha fetoprotein levels were associated with worse survival, but a higher radiation dose improved the survival.