title: Phase I dose escalation study of helical intensity-modulated radiotherapy-based stereotactic body radiotherapy for hepatocellular carcinoma.
abstract: BACKGROUND
  Phase I trial was conducted to determine feasibility and toxicity of helical intensity-modulated radiotherapy (IMRT)-based stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).
  
  
  RESULTS
  Eighteen patients (22 lesions) were enrolled. With no DLT at 52 Gy (13 Gy/fraction), protocol was amended for further escalation to 60 Gy (15 Gy/fraction). Radiologic complete response rate was 88.9%. Two outfield intrahepatic, 2 distant, 4 concurrent local and outfield, and 1 concurrent local, outfield and distant failures (no local failure at dose levels 3-4) occurred. The worst toxicity was grade 3 hematologic in five patients, with no gastrointestinal toxicity > grade 1. At median follow-up of 28 months for living patients, 2-year local control, progression-free (PFS), and overall survival rates were 71.3%, 49.4% and 69.3%, respectively. Multi-segmental recurrences prior to SBRT was independent prognostic factor for PFS (p = 0.033).
  
  
  METHODS
  Eligible patients had Child-Pugh's class A or B, unresectable HCC, ≤ 3 lesions, and cumulative tumor diameter ≤ 6 cm. Starting at 36 Gy in four fractions, dose was escalated with 2 Gy/fraction per dose-level. CTCAE v 3.0 ≥ grade 3 gastrointestinal toxicity and radiation induced liver disease defined dose-limiting toxicity (DLT).
  
  
  CONCLUSIONS
  Helical IMRT-based SBRT was tolerable and showed encouraging results. Confirmatory phase II trial is underway.
authors.affiliation: Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jun Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jinsil
authors.initials: J
authors.lastname: Seong
authors.affiliation: Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ik Jae
authors.initials: IJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joong Yeol
authors.initials: JY
authors.lastname: Woo
authors.affiliation: Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D011874:Radiometry; D016634:Radiosurgery / Q000379:methods*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D016896:Treatment Outcome
keywords: dose escalation; hepatocellular carcinoma; intensity-modulated radiotherapy; stereotactic body radiotherapy