11028 Background: HDMTX followed by leucovorin rescue is well established as part of MAP chemotherapy for osteosarcoma. However, leucovorin rescue is not always effective as rescue, resulting in delays to subsequent courses of chemotherapy. Methods: This retrospective observational study involved patients ≥2 years of age with osteosarcoma treated with MAP during 2009 - 2014. Data was extracted from medical records from five clinics in Poland, Hungary, Norway and Sweden. The study objective was to determine to what extent patients treated with MAP encountered treatment delays due to MTX-related toxicity or delayed MTX elimination. Results: All patients fulfilling the inclusion criteria were included. Of 116 patients (ages 5-39 with a mean of 14 years; 59% males), 97% completed their first MAP cycle while only 48% completed six treatment cycles. The analysis of the primary endpoint included 114 evaluable patients. At least one treatment delay due to MTX toxicity or delayed MTX elimination was reported for 89 patients (78%) and only six patients (5%) completed the entire MAP treatment according to plan. Delay in subsequent treatment was observed following 183 of 369 evaluated MAP cycles (50%). About three quarters of the delays were found to be due to MTX-related toxicity while only a small number were related to delayed MTX elimination. The treatment related issues most commonly registered were increased liver enzymes, hematological disturbances, increased bilirubin and mucositis. Conclusions: We found at least one treatment delay due to MTX toxicity or delayed MTX elimination in 78% of all MAP-treated patients and that 50% of the administered MAP cycles resulted in a delay in subsequent treatment, mostly due to MTX toxicity. Only six patients (5%) completed the entire MAP treatment according to plan. The retrospective methodology with broad inclusion criteria implies that the results can be extrapolated to the entire target population. Thus, there appears to be an unmet need for a more effective HDMTX rescue that could reduce MTX toxicity and be expected to enable more patients to maintain planned MAP treatment intensity and duration, thereby improving the overall efficacy of the MAP regimen.