Inclusion Criteria:  Diagnosis of high grade OS of the extremities Age at diagnosis ≤ 40 years at the time of diagnosis Localized disease (skip metastases are allowed) Adequate organ function according the AIEOP/ISG OS 2021 recommendation Patients or parents oe guardians of minors who have given their written informed consent to participate in the study  Exclusion Criteria:  Presence of metastases Diagnosis of periosteal OS, of parosteal OS or secondary OS Any medical condition which can not allowed the use of the treatments recommended by AIEOP/ISG OS 2021