title: The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma.
abstract: OBJECTIVE
  Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients with localized bone sarcomas and to adjust for potential confounders.
  
  
  METHODS
  All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils, lymphocytes, and sodium were collected from the patient records. The prognostic values of overall and disease-specific mortality were tested for each individual biomarker as well as for the Glasgow prognostic score (GPS) and for a new composite score incorporating five biomarkers (Aarhus composite biomarker score: ACBS). Adjustments were made for comorbidity as well as other possible prognostic factors, such as size, histological type, margin, chemotherapy, and soft tissue extension, using the Cox proportional hazard model.
  
  
  RESULTS
  A total of 172 patients with high- or intermediate-grade localized bone sarcoma were included. Of these patients, 63 were diagnosed with chondrosarcoma and 109 patients with Ewing/osteosarcoma. The median age was 55 years for chondrosarcoma and 19 years for Ewing/osteosarcoma patients. The overall 5-year mortality was 31% [95% confidence interval (CI): 21-44] and 41% (95% CI: 33-51), whereas the 5-year disease-specific mortality was 21% (95% CI: 12-34) and 39% (95% CI: 31-49) for chondrosarcoma and Ewing/osteosarcoma, respectively. Comorbidities were present in 12% of the Ewing/osteosarcoma patients and in 24% of the chondrosarcoma patients. After adjustment for comorbidity and other confounders, it was found that elevated levels of CRP, low hemoglobin, low sodium, high GPS, and high ACBS were associated with increased overall mortality. Furthermore, elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were associated with increased disease-specific mortality.
  
  
  CONCLUSIONS
  Elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were all independent prognostic factors for both overall and disease-specific mortality. ACBS is a new three-level score of five biomarkers, but its value has to be confirmed in an independent data set.
authors: Department of Oncology, Sarcoma Centre of Aarhus University Hospital, Aarhus, Denmark; Department of Experimental Clinical Oncology, Sarcoma Centre of Aarhus University Hospital, Aarhus, Denmark. Electronic address: ninnpe@rm.dk.
authors: Ninna
authors: N
authors: Aggerholm-Pedersen
authors: Department of Experimental Clinical Oncology, Sarcoma Centre of Aarhus University Hospital, Aarhus, Denmark.
authors: Katja
authors: K
authors: Maretty-Kongstad
authors: Department of Orthopaedic Surgery, Sarcoma Centre of Aarhus University Hospital, Aarhus, Denmark.
authors: Johnny
authors: J
authors: Keller
authors: Department of Pathology, Sarcoma Centre of Aarhus University Hospital, Aarhus, Denmark.
authors: Steen
authors: S
authors: Baerentzen
authors: Department of Oncology, Sarcoma Centre of Aarhus University Hospital, Aarhus, Denmark.
authors: Akmal
authors: A
authors: Safwat