title: A mouse radiation-induced liver disease model for stereotactic body radiation therapy validated in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  Lower radiation tolerance of the whole liver hinders dose escalations of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) treatment. This study was conducted to define the exact doses that result in radiation-induced liver disease (RILD) as well as to determine dose constraints for the critical organs at risk (OARs) in mice; these parameters are still undefined in HCC SBRT.
  
  
  METHODS
  This study consisted of two phases. In the primary phase, mice treated with helical tomotherapy-based SBRT were stratified according to escalating radiation doses to the livers. The pathological differences, signs [such as mouse performance status (MPS)], and serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/albumin levels were observed. Radiation-induced disease severities of the OARs were scored using systematic evaluation standards. In the validation phase in humans, 13 patients with HCC who had undergone radiotherapy before hepatectomy were enrolled to validate RILD pathological changes in a mouse study.
  
  
  RESULTS
  The evaluation criteria of the mouse liver radiotherapy-related signs were as follows: MPS ≥ 2.0 ± 0.52, AST/ALT ≥ 589.2 ± 118.5/137.4 ± 15.3 U/L, serum albumin ≤ 16.8 ± 2.29 g/L. The preliminary dose constraints of the OARs were also obtained, such as those for the liver (average dose ≤ 26.36 ± 1.71 Gy) and gastrointestinal tract (maximum dose ≤ 22.63 Gy). Mouse RILD models were able to be developed when the livers were irradiated with average doses of ≥31.76 ± 1.94 Gy (single fraction). RILD pathological changes in mice have also been validated in HCC patients.
  
  
  CONCLUSIONS
  Mouse RILD models could be developed with SBRT based on the dose constraints for the OARs and evaluation criteria of mouse liver radiotherapy-related signs, and the authors' results favor the study of further approaches to treat HCC with SBRT.
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Shen
authors.affiliation: Department of Radiation Oncology, The 4th Affiliated Hospital, Soochow University, Wuxi, Jiangsu 214062, China.
authors.forename: Le-Yuan
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Ya-Bo
authors.initials: YB
authors.lastname: Gao
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
authors.forename: Zhao-Chong
authors.initials: ZC
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy / Q000601:surgery; D004307:Dose-Response Relationship, Radiation; D005260:Female; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008099:Liver / Q000473:pathology / Q000528:radiation effects* / Q000601:surgery; D008107:Liver Diseases / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D008297:Male; D008813:Mice, Inbred ICR; D008875:Middle Aged; D058958:Organs at Risk; D011833:Radiation Injuries, Experimental / Q000097:blood; D016634:Radiosurgery / Q000009:adverse effects* / Q000379:methods; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D011897:Random Allocation
chemical_list: D000418:Albumins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase