title: Three-dimensional conformal radiation therapy and intensity-modulated radiation therapy combined with transcatheter arterial chemoembolization for locally advanced hepatocellular carcinoma: an irradiation dose escalation study.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) of three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with transcatheter arterial chemoembolization for locally advanced hepatocellular carcinoma.
  
  
  METHODS
  Patients were assigned to two subgroups based on tumor diameter: Group 1 had tumors <10 cm; Group II had tumors ≥10 cm. Escalation was achieved by increments of 4.0 Gy for each cohort in both groups. Dose-limiting toxicity (DLT) was defined as a grade of ≥3 acute liver or gastrointestinal toxicity or any grade 5 acute toxicity in other organs at risk or radiation-induced liver disease. The dose escalation would be terminated when ≥2 of 8 patients in a cohort experienced DLT.
  
  
  RESULTS
  From April 2005 to May 2008, 40 patients were enrolled. In Group I, 11 patients had grade ≤2 acute treatment-related toxicities, and no patient experienced DLT; and in Group II, 10 patients had grade ≤2 acute toxicity, and 1 patient in the group receiving 52 Gy developed radiation-induced liver disease. MTD was 62 Gy for Group I and 52 Gy for Group II. In-field progression-free and local progression-free rates were 100% and 69% at 1 year, and 93% and 44% at 2 years, respectively. Distant metastasis rates were 6% at 1 year and 15% at 2 years. Overall survival rates for 1-year and 2-years were 72% and 62%, respectively.
  
  
  CONCLUSIONS
  The irradiation dose was safely escalated in hepatocellular carcinoma patients by using 3DCRT/IMRT with an active breathing coordinator. MTD was 62 Gy and 52 Gy for patients with tumor diameters of <10 cm and ≥10 cm, respectively.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, China, 200032.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Ren
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Zhao
authors.forename: Ke
authors.initials: K
authors.lastname: Gu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Lin
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Xu
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Hu
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Zhou
authors.forename: Lu-Ming
authors.initials: LM
authors.lastname: Liu
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D047368:Tumor Burden