order SB 203580 hydrochloride Implementation of contemporary
Implementation of contemporary treatment protocols, incorporating adjuvant chemotherapy, have resulted in an improvement in the prognosis of patients diagnosed with osteosarcoma over the past decades. The overall 5-year survival rate has improved from less than 20% in the 1960s to approximately 60% . The prognosis, however, remains unsatisfactory in cases with metastases, with an overall 5-year survival rate of less than 30% . Owing to the fact that long-term survival can be improved to over 40%, the European Society of Medical Oncology (ESMO) recommends mandatory excision of all metastatic lesions in patient diagnosed with osteosarcoma [8,9]. It is therefore essential that all patients with metastatic disease are identified timeously. In addition, there is a need for markers which identify patients with a poor prognosis so that more aggresive treatment options can be implemented in an effort to improve their prognosis .
Results Sixty-seven patients were identified with histologically confirmed osteosarcoma involving an extremity. Six patients were excluded from study. One patient passed away prior to completion of systemic staging investigations and five patients were diagnosed with osteosarcoma variants. Sixty-one patients met the inclusion criteria and their clinical characteristics are listed in table 1. The mean patient age was 21 years (standard deviation [SD] 11.9 years) and there was an equal distribution between male and female patients (50.8 vs 49.2%). The incidence of pulmonary and skeletal metastases did not vary significantly according to the age (p=0.16 and p=0.27, respectively). The majority of patients (98%) where of African descent. The order SB 203580 hydrochloride (57%) and tibia (31%) were involved in the majority of cases. Only 19.7% (n=12) of patients had no evidence of metastatic disease at time of presentation. Seventy-two percent (n=44) had pulmonary metastases. No other visceral metastases, including liver metastases, were detected on the chest and abdominal CT-scans. Twenty eight percent (n=16) of patients who had a bonescan had evidence of skeletal metastases at the time of presentation. The incidence of pulmonary and skeletal metastases did not vary significantly according to patient age (p=0.10 and p=0.14, respectively). The serum levels of LDH were not significantly different in patients with or without pulmonary metastases (p=0.88 and p=0.47, respectively) (Table 2). The serum LDH and ALP levels did however differ significantly in patients with or without skeletal metastases (p<0.001 and p=0.02, for LDH and ALP, respectively). Optimal breakpoint analysis of serum LDH as a predictor of pulmonary metastases revealed an area under the receiver operator curve (AUC) of 0.569 (Fig. 1). 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) (Fig. 1). Serum LDH of 454 IU/L equated to 100% sensitivity for detected bone metastases with a positive diagnostic likelihood ratio (DLR) of 1.32 (95% CI 1.1–1.6). The optimal breakpoint analysis of ALP and pulmonary metastases revealed poor correlation (AUC 0.516). The optimal breakpoint for serum ALP as a marker of skeletal metastases was 283 IU/L (AUC 0.771; sensitivity=0.81; specificity=0.76) (Fig. 2). A serum ALP level of 76 IU/l was 100% sensitive in predicting the presence of skeletal metastases (positive DLR 1.1; 95% CI 1.0–1.2). Logistic regression analysis confirmed antigens serum LDH and ALP were significant prognostic factors for skeletal metastases at time of presentation. Univariate analysis of serum LDH >850 IU/L revealed an odds ratio (OR) of 10.9 (95% CI 2.6–46.1) for the presence of skeletal metastases (p<0.01) and for serum ALP >280 IU/L the OR was 12.4 (95% CI 2.9–53.0). In a multivariate analysis of serum ALP and LDH both factors remained predictive of skeletal metastases. However, with the addition of pre-treatment tumour volume LDH lost its significance (Table 3).