title: Liver metastases from cancer of unknown primary (CUPL): a retrospective analysis of presentation, management and prognosis in 49 patients and systematic review of the literature.
abstract: OBJECTIVE
  Patients with liver metastases from cancer of unknown primary (CUPL) have a dismal prognosis. We retrospectively analysed their management and outcome and performed a systematic review of CUPL series published in the literature.
  
  
  METHODS
  Electronic data from 49 CUPL patients referred to Hellenic Cooperative Oncology Group (HeCOG) centers were retrospectively studied for characteristics of clinical presentation, diagnostic workup, management, outcome and prognostic factors. A systematic literature review was undertaken in PubMed and EmBase databases.
  
  
  RESULTS
  All our patients (males: 31, females: 18; median age: 65) underwent a computed tomography scan (CT) of the abdomen, 71% a thoracic CT, 53% gastroscopy and 47% colonoscopy. The commonest histologic subtypes encountered were adenocarcinoma (N=34) or undifferentiated carcinoma (N=12). The liver was the only metastatic site in 38% of patients, while it was accompanied with other metastatic sites in 62% (the commonest: lung, bone and lymph nodes). Forty-seven patients received first-line chemotherapy (42 platinum based) and 16 second-line. An objective response was observed in six patients (12%), median survival being 10 months (95% CI, 7-13). In univariate analysis, good performance status and normal baseline serum CEA levels were correlated with superior survival, while in multivariate analysis only age<55 (HR 0.16, p=0.02) and the absence of extrahepatic disease (HR 0.21, p=0.007) predicted for a better outcome. Published data from four relevant series (total patients=662) parallel our findings.
  
  
  CONCLUSIONS
  Patients with liver metastases from CUP are resistant to conventional types of treatment and carry a poor prognosis. Understanding the molecular biology of CUP is essential for the development of new, targeted effective therapies.
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Niarxou Avenue, 45500 Ioannina, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Lazaridis
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001707:Biopsy, Needle; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D016015:Logistic Models; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy / Q000473:pathology*; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed