title: Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis.
abstract: OBJECTIVE
  To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC).
  
  
  METHODS
  Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractions over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization.
  
  
  RESULTS
  At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group.
  
  
  CONCLUSIONS
  This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are significantly fewer hospitalization days after proton treatment, which may indicate reduced toxicity with proton beam therapy.
authors.affiliation: Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California. Electronic address: dbush@llu.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Bush
authors.affiliation: Department of Diagnostic Radiology, Loma Linda University Medical Center, Loma Linda, California.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Smith
authors.affiliation: Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California.
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Slater
authors.affiliation: Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Volk
authors.affiliation: VA Loma Linda Health Care System, Loma Linda, California.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Reeves
authors.affiliation: Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California.
authors.forename: Jason
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California.
authors.forename: Roger
authors.initials: R
authors.lastname: Grove
authors.affiliation: Transplantation Institute and Liver Center, Loma Linda University Medical Center, Loma Linda, California.
authors.forename: Michael E
authors.initials: ME
authors.lastname: de Vera
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods* / Q000401:mortality; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004998:Ethiodized Oil / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D061766:Proton Therapy / Q000379:methods* / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D004998:Ethiodized Oil