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.

Tempting results of preliminary reports from EURAMOS-1 Study Group and our willingness to join the Consortium were the reason why we decided to start the pilot study exploit EURAMOS-1 protocol (approved by Local Ethical Commission).

Since November 2006, 41 patients were enrolled into study (20F/21M, mean age: 14, SD: 3,02) but 1 adolescent refused the treatment at all in 2nd week on. The main localization was thigh (20/41, 49%), followed by tibia (15/41, 37%), fibula (3/41, 7%) and humerus (3/41, 7%).

Majority of them had localized disease (27/41, 66%), whereas in 34% (14/41) lung metastases (LM) were revealed at diagnosis. Out of 40, 35 underwent surgery (2 amputations, 33 endoprosthesis) in 11th protocol week as average (mean: 12, SD: 2.80). Among the remaining 5 children, 4 progressed yet during neo-adjuvant CHT and 1 had to finish because of MTX intolerance. Up to now HP examination were completed in 29 children and the median of 12% of viable tumor cells remains (mean: 13%, SD: 22.32%; min. < 1%, max. 90%). Fourteen (48%) good responders continued on MAP arm. Children in whom poor HP response has been confirmed as well as all children with LM, received chemotherapy according to MAPIE arm. The switch between MAP and MAPIE proceeded in 18th week of protocol in average (median: 17th; nim. 14th, max. 24th week). Up to date, in 5 out of 21 patients completed the protocol, the treatment had to be finished untimely because of toxicity and further 5 required CHT switch because of progression.

Comparing achieved HP responses with previous experiences, we found no statistically significant differences in rate of tumor necrosis in current study (48%) as in previously used regimens (EORTC 49% and SFOP 44%; OR{EURAMOS/EORTC}=0.96; OR {EURAMOS/SFOP}=1.17; chi-square=0.343, p=0.842), but the general remarks from the pilot justify study’s continuation.