Post-authorization, observational, multicenter and prospective study in patients between 2 and 30 years old diagnosed with non-metastatic high-grade osteosarcoma of the extremities.

All patients included in the study will receive the initial neoadjuvant treatment prescribed by the doctor of each center, according to standard practice (involving methotrexate, cisplatin, and adriamycin). This initial treatment precedes surgical treatment.

After surgical treatment, the histological response to neoadjuvant chemotherapy will be evaluated. The histological response to primary chemotherapy will be expressed as a percentage of tumor necrosis. In the case of tumor necrosis above 90% the patient is defined as a "good responder" in case of a lower percentage as a "poor responder".

As an adjuvant treatment, the following options may be given according to standard practice in each center:

1. - If there is overexpression of ABCB1 / P-glycoprotein and poor response to induction treatment, in many sites ifosfamide at high doses and MTP-PE, is incorporated in addition to adriamycin.
2. - If there is overexpression of ABCB1 / P-glycoprotein and a good response to induction treatment, in many centers the option of additional administration of methotrexate, CDDP and adriamycin will be chosen.
3. - If there is no overexpression of ABCB1 / P-glycoprotein, the administration of methotrexate, adriamycin and cisplatin will be chosen in many sites.

In some sites they will consider the non-administration of MTP-PE or the non-administration of high doses of ifosfamide. And, in some hospitals, they will consider administering MTP-PE to all patients.

The Primary objective is:

- Disease-free survival measured as a 5-year rate in patients with localized osteosarcoma treated, according to standard practice, with all the drugs currently registered for the treatment of non-metastatic osteosarcoma (methotrexate, cisplatin, adriamycin, ifosfamide, MTP-PE), according to ABCB1 / P-glycoprotein expression.

The Secondary objectives are:

• Evaluate overall survival in a homogeneous population of patients with non-metastatic osteosarcoma.
• Disease-free survival at 2 and 3 years.

Inclusion Criteria:

1. Confirmed histological diagnosis of high-grade osteosarcoma of the extremities.
2. Age: from 2 to 30 years old.
3. Localized disease (metastasis skip accepted).
4. Normal liver, kidney and spinal function.
5. Ventricular ejection fraction of 50%.
6. Absence of previous surgical treatments or chemotherapy for osteosarcoma.
7. Interval between histological diagnosis and initiation of chemotherapy not exceeding 4 weeks.
8. Signing of the consent form to participate in the study.

Exclusion Criteria:

1. Presence of lung metastases on chest CT or in other locations.
2. Parosteal, periosteal, or secondary osteosarcoma.
3. Contraindications of the medications prescribed in the protocol.
4. Pregnant or lactating.
5. Mental or social conditions that do not guarantee adequate adherence to the protocol.
6. Not having an adequate understanding of study participation.

Patients from 2 to 30 years old diagnosed with non-metastatic high-grade osteosarcoma of the extremities.