title: Pre-treatment serum lactate dehydrogenase and alkaline phosphatase as predictors of metastases in extremity osteosarcoma.
abstract: BACKGROUND
  The prognosis of patients with metastatic osteosarcoma remains poor. However, the chance of survival can be improved by surgical resection of all metastases. In this study we investigate the value of serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in predicting the presence of metastatic disease at time of diagnosis.
  
  
  METHODS
  Sixty-one patients with histologically confirmed conventional osteosarcoma of the extremity were included in the study. Only 19.7% of cases presented without evidence of systemic spread of the disease. Pre-treatment serum ALP and LDH were analysed in patients with and without skeletal or pulmonary metastases.
  
  
  RESULTS
  Serum LDH and ALP levels were not significantly different in patients with or without pulmonary metastases (p=0.88 and p=0.47, respectively). The serum LDH and ALP levels did however differ significantly in patients with or without skeletal metastases (p<0.001 and p=0.02, respectively). The optimal breakpoint for serum LDH as a marker of skeletal metastases was 849 IU/L (AUC 0.839; Sensitivity=0.88; Specificity=0.73). LDH >454 IU/L equated to 100% sensitivity for detected bone metastases (positive diagnostic likelihood ratio (DLR)=1.32). With a cut-off of 76 IU/L a sensitivity of 100% was reached for serum ALP predicting the presence of skeletal metastases (positive DLR=1.1). In a multivariate analysis both LDH ≥850 IU/L (odds ratio [OR]=9; 95% confidence interval (CI) 1.8-44.3) and ALP ≥280 IU/L (OR=10.3; 95% CI 2.1-50.5) were predictive of skeletal metastases. LDH however lost its significance in a multivariate model which included pre-treatment tumour volume.
  
  
  CONCLUSIONS
  In cases of osteosarcoma with LDH >850 IU/L and/or ALP >280 IU/L it may be prudent to consider more sensitive staging investigations for detection of skeletal metastases. Further research is required to determine the value and the most sensitive cut-off points of serum ALP and LDH in the prediction of skeletal metastases.
authors.affiliation: Tumor, Sepsis and Reconstruction Unit, Department of Orthopaedic Surgery, Greys Hospital, School of Clinical Medicine, University of KwaZulu-Natal, South Africa.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Marais
authors.affiliation: Department of Orthopaedic Surgery, Edendale Hospital, School of Clinical Medicine, University of KwaZulu-Natal, South Africa.
authors.forename: Julia
authors.initials: J
authors.lastname: Bertie
authors.affiliation: Perioperative Research Group, Department of Anaesthetics, Grey's Hospital, School of Clinical Medicine, University of KwaZulu-Natal, South Africa.
authors.forename: Reitze
authors.initials: R
authors.lastname: Rodseth
authors.affiliation: Public Health Medicine, School of Nursing and Public Health, College of Health Sciences, University of KwaZulu-Natal, South Africa.
authors.forename: Benn
authors.initials: B
authors.lastname: Sartorius
authors.affiliation: Tumor, Sepsis and Reconstruction Unit, Department of Orthopaedic Surgery, Greys Hospital, School of Clinical Medicine, University of KwaZulu-Natal, South Africa.
authors.forename: Nando
authors.initials: N
authors.lastname: Ferreira
keywords: ALP, alkaline phosphatase; AUC, area under curve; Alkaline phosphatase; CI, confidence interval; CT, computed tomography; DLR, diagnostic likelihood ratio; ESMO, European Society of Medical Oncology; FDG-PET, 18F-fluorodeoxy-D-glucose positron emission tomography; LDH, lactate dehydrogenase; Lactate dehydrogenase; MRI, magnetic resonance imaging; Metastases; OR, odds ratio; Osteosarcoma; Prognosis; ROC, Receiver operating characteristic; SD, standard deviation; SEER, Surveilance, Epidemiology and End Results; Staging