title: High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma.
abstract: BACKGROUND
  Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC.
  
  
  METHODS
  Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0-7.0 cm), and the median dose was 51 Gy (range, 33-60 Gy).
  
  
  RESULTS
  LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45-54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT.
  
  
  CONCLUSIONS
  This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.
authors.forename: Won Il
authors.initials: WI
authors.lastname: Jang
authors.affiliation: Department of Radiation Oncology, Korea Institute of Radiological & Medical Science, Seoul, Republic of Korea. mskim@kirams.re.kr.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Sun Hyun
authors.initials: SH
authors.lastname: Bae
authors.forename: Chul Koo
authors.initials: CK
authors.lastname: Cho
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Yoo
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Seo
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Kang
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Dong Han
authors.initials: DH
authors.lastname: Lee
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Han
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Su Cheol
authors.initials: SC
authors.lastname: Park
authors.forename: Sang Bum
authors.initials: SB
authors.lastname: Kim
authors.forename: Eung-Ho
authors.initials: EH
authors.lastname: Cho
authors.forename: Young Han
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000532:radiotherapy*; D016461:Chemoembolization, Therapeutic; D015331:Cohort Studies; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D011336:Probability; D016634:Radiosurgery / Q000379:methods*; D012189:Retrospective Studies; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome