title: Long-term therapy with sorafenib is associated with pancreatic atrophy.
abstract: BACKGROUND
  Although the short-term adverse effects of sorafenib are well known, few data exist on long-term toxicity. The objective of the present study was to investigate the prevalence of pancreatic atrophy among a cohort of patients with hepatocellular carcinoma (HCC) who were treated with sorafenib for ≥2 y.
  
  
  METHODS
  Between March 2007 and December 2013, 31 patients with HCC who were treated with sorafenib for ≥2 y were identified. The effect of pancreatic atrophy and enhancement on incidence of adverse events, tumor response, and overall survival (OS) were assessed.
  
  
  RESULTS
  Thirty-one patients with HCC were treated with sorafenib for ≥2 y and met inclusion criteria; 11 patients (35.5%) were Barcelona-clinic liver cancer stage B, whereas 20 patients (64.5%) were Barcelona-clinic liver cancer stage C. Median duration of treatment with sorafenib was 35.2 mo. Pancreatic atrophy and a decrease in pancreatic enhancement occurred in 24 patients (77.4%) and 15 patients (48.4%), respectively. On the basis of the modified response evaluation criteria in solid tumors, four patients (12.9%) had a complete response, 10 patients (32.3%) had a partial response, and 17 patients (54.8%) had stable disease. Patients treated with sorafenib with pancreatic atrophy had a median OS of 49.4 mo (95% confidence interval, 41.2-57.5 mo) compared with 31.2 mo (95% confidence interval, 25.7-36.7 mo) among patients who did not develop pancreatic atrophy (P = 0.009). In contrast, survival was not associated with decreased versus normal enhancement of the pancreas (OS, 47.7 mo versus 41.7 mo, respectively; P = 0.739).
  
  
  CONCLUSIONS
  Pancreatic atrophy occurred in many HCC patients after 2 y of treatment with sorafenib. Patients who experienced pancreatic atrophy had a better tumor response and OS.
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Imaging and Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gaya
authors.initials: G
authors.lastname: Spolverato
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yao-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: chminsh@mail.sysu.edu.cn.
authors.forename: Min-Shan
authors.initials: MS
authors.lastname: Chen
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001284:Atrophy / Q000139:chemically induced; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010179:Pancreas / Q000473:pathology; D010182:Pancreatic Diseases / Q000139:chemically induced* / Q000473:pathology; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Hepatocellular carcinoma; Late toxicity; Pancreatic atrophy; Sorafenib