Serum level of the extracellular domain of HER-2 (ECD/HER2) has been suggested to be a tumor marker in breast cancer. The aim of this study was to assess the prognostic value of baseline level of ECD/HER2 and changes in levels over time in children and adults with osteosarcoma during chemotherapy.

Materials and methods: We analysed 33 newly-diagnosed osteosarcoma patients treated at the Department of Paediatric Oncological Surgery of the Institute of Mother and Child, Warsaw, Poland between 2005–2008. Patients characteristics: age 8–18 years (median 15); staging at diagnosis: disease localised (18) and dissemination (15); disease progression (13); deaths (6). Follow-up: 8–37 months (median 19). ECD/HER2 was measured in 118 serum samples using a validated ELISA kit: at the time of diagnosis (1), after preoperative chemotherapy (2), 2 weeks after surgery (3) and 3–6 moths after surgery (4).

Results: The baseline level of ECD/HER-2 in serum ranged 3.8–34.4 ng/mL (median 5). The elevated baseline ECD/HER2 was associated with decreased progression free survival (ECD/HER2 ng/mL> 5 vs ECD/HER2 ng/mL≤5: 44% vs 77%; p=0.039) and decreased overall survival (ECD/HER2 ng/mL> 5 vs ECD/HER2 ng/mL≤5: 69% vs 94%, p=0.115). The concentration of ECD/HER2> 6 ng/ml during treatment (specially postoperative chemotherapy) was associated with early disease progression (p=0.095).

Conclusions: The high level of ECD/HER2 at the time of diagnosis may be a marker of poor prognosis in osteosarcoma. Additionally, we suggest that changes of this marker concentration over time could be helpful for treatment monitoring.

In osteosarcoma, treatment guidelines recommend standard chemotherapy regardless of severity of disease. Treatment individualization will minimize risk of failure and adverse effects, specially in patients who have good prognosis. Therefore, there is a pressing clinical need to develop a risk adapted strategies and to adjust chemotherapy to prognostic factors.

Aim: to asses usefulness of Classification and Regression Tree Analysis (C& RT) for stratifying patients with localised osteosarcoma to the risk groups according to clinical and biological markers.

Material and methods: 100 patients with localised osteosarcoma were included, aged 5–23 years (mean 14), with extremity localisation of the primary tumour. Follow up – at least 5 years since a date of diagnosis. We analysed clinical prognostic factors (tumour size, pathological fracture, alkaline phosphatase, age), histological prognostic factors (% of viable tumour cells after pre-operative chemotherapy, subtype of osteosarcoma and its aggressiveness) and biological factors (expression of VEGF, Ki-67, Topoisomerase II alpha and P glycoprotein). The expressions of proteins were measured immunohistochemically in biopsy samples. C& RT model included all described above factors.

Results: C& RT analysis revealed that the most important prognostic factors in localised osteosarcoma were: VEGF, Topoisomerase II alpha and tumour size. This markers were included into the risk classification and three risk groups were proposed: with poor prognosis (n=13) – 5 year OS 31%, moderate (n=57) – 5 year OS 63% and with good prognosis (n=30) – 5 year OS 93%), P=0.000.

Conclusion: C& RT is useful method for stratifying patients with osteosarcoma to risk groups. The stratification should include biological and clinical prognostic markers.