title: Identification of clinical biomarkers for patients with advanced hepatocellular carcinoma receiving sorafenib.
abstract: BACKGROUND
  Identification of patients with advanced HCC-deriving preferential benefit from sorafenib is desirable, and treatment-related adverse events are potential clinical biomarkers.
  
  
  METHODS
  Survival and toxicity data for patients with HCC treated with sorafenib at the Christie NHS Foundation Trust from 11/09 to 02/15 were collected retrospectively.
  
  
  RESULTS
  Eighty-five eligible patients were identified. The most common grade 3 or 4 treatment-related toxicities were hypertension (HTN, 45 %), fatigue (8 %), and hand-foot syndrome (HFS, 8 %). Any-grade HFS and/or worsening HTN (HFS/HTN) were experienced by 58 % of patients. Estimated median progression-free and overall survival (OS) were 4.6 (95 % CI 2.8-5.2) and 6.5 (95 % CI 4.9-8.01) months, respectively. Child-Pugh score (p value <0.001) and the development of HFS/HTN were independent prognostic factors impacting on OS on multivariable analysis. Patients who developed HFS/HTN had median OS of 8.2 months (95 % CI 6.5-12.4) compared with 4.1 (95 % CI 2.7-5.4) for those without this toxicity (Hazard Ratio (HR) 0.4, 95 % CI 0.2-0.7, p value 0.003). The prognostic impact of HFS/HTN was confirmed by landmark analyses limited to patients who lived a minimum of 2 months (p value 0.019) or who developed HFS/HTN in the first 3 months of treatment (p value 0.006).
  
  
  CONCLUSIONS
  The development of toxicities specific to sorafenib is associated with prolonged survival in a UK-based HCC patient series; prospective assessment of their significance is required.
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Lamarca
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.|Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: O
authors.initials: O
authors.lastname: Abdel-Rahman
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: I
authors.initials: I
authors.lastname: Salu
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.|Institute of Cancer Sciences, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Manchester, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: McNamara
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.|Institute of Cancer Sciences, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Manchester, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Valle
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. richard.hubner@christie.nhs.uk.
authors.forename: R A
authors.initials: RA
authors.lastname: Hubner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D000077157:Sorafenib; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Biomarker; Clinical; Hepatocellular carcinoma (HCC); Sorafenib; Survival; Toxicity