title: Prognosis of patients with advanced hepatocellular carcinoma who failed first-line systemic therapy.
abstract: OBJECTIVE
  No approved therapy is available for patients with advanced hepatocellular carcinoma (HCC) who fail first-line therapy. The prognosis of these patients, especially those eligible for clinical trials of second-line therapy, is unclear.
  
  
  METHODS
  All patients who participated in clinical trials of first-line systemic therapy for metastatic or locally advanced HCC in a referral center of Taiwan between 2005 and 2011 were included. Their clinicopathologic characteristics, when the first-line treatment failed, were analyzed and correlated with the overall survival (OS) from the date of first-line treatment failure.
  
  
  RESULTS
  A total of 192 patients were included. Before the start of the first-line therapy, all patients had Child-Pugh class A liver reserves and Cancer of the Liver Italian Program (CLIP) scores ≤4. After the failure of the first-line therapy, the median OS of the entire group was 4.0 months. Patients with Child-Pugh class A liver reserves, when the first-line treatment failed, had significantly better OS than patients with Child-Pugh class B or C liver reserves (median, A vs. B vs. C=7.5 vs. 1.3 vs. 1.0 month, p<0.001). According to the key eligibility criteria of 3 published clinical trials for second-line therapy, 41%-56% of patients were potentially eligible. Compared to patients who were ineligible for clinical trials, potentially eligible patients had longer OS with a median of 7.8-8.6 months.
  
  
  CONCLUSIONS
  Patients with advanced HCC who failed first-line therapy could have substantially improved prognosis if they had Child-Pugh A liver reserves or were potentially eligible for clinical trials.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Shao
authors.affiliation: Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Imaging, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan.
authors.forename: Chih-Horng
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Lu
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Soa-Yu
authors.initials: SY
authors.lastname: Chan
authors.affiliation: National Taiwan University Cancer Center Preparatory Office, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Yi
authors.initials: YY
authors.lastname: Ma
authors.affiliation: National Taiwan University Cancer Center Preparatory Office, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Feng-Chu
authors.initials: FC
authors.lastname: Yen
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: chihhunghsu@ntu.edu.tw.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013624:Taiwan / Q000453:epidemiology; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
keywords: BCLC; Barcelona Clinic Liver Cancer; CLIP; Cancer of the Liver Italian Program; Clinical trials; ECOG PS; Eastern Cooperative Oncology Group performance status; HCC; Hepatocellular carcinoma; NTUH; National Taiwan University Hospital; OS; Prognosis; Second-line therapy; Survival; TTP; hepatocellular carcinoma; overall survival; time to progression