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Before injection of methotrexate, the patient must be counseled extensively on the risks, benefits, and adverse effects of the treatment and on the possibility of failure of medical therapy, which would result in tubal rupture and necessitate surgery.

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in combination with other chemotherapeutic agents, high dose methotrexate doses followed by leucovorin rescue may be effective in prolonging relapse-free survival in patients with non-metastatic osteosarcoma.