title: Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryo Nakata, Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryo Nakata, Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryo Nakata, Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Taniguch
authors.affiliation: Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryo Nakata, Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Nomura
authors.affiliation: Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryo Nakata, Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Sato
authors.affiliation: Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryo Nakata, Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Suzuki
authors.affiliation: Hiroyuki Kato, Hideo Yoshida, Hiroyoshi Taniguch, Ryo Nakata, Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D004867:Equipment Design; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D011829:Radiation Dosage; D016634:Radiosurgery / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D012189:Retrospective Studies; D012307:Risk Factors; D013525:Surgical Instruments; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C097353:AFP protein, human; D015415:Biomarkers; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin
keywords: Cyberknife; Hepatocellular carcinoma; Liver radiotherapy; Neoplasm metastasis/therapy; Stereotactic body radiotherapy