The purpose of this study is to learn whether the profile of RNA from circulating exosomes can be used as a biomarker for lung metastases of primary high-grade osteosarcoma. Circulating exosomes plays roles in metastases in many kinds of cancer including osteosarcoma. By RNA profiling researchers may find lung metastases earlier than conventional work-up and predict the oncological outcomes.

Investigators have performed a 4 patients pilot study under the oversight of hospital's ethics committee, and investigator found that the levels and mutations of circulating exosome RNA from patients with or without lung metastasis have significant differences. Then investigators wish to register this study to do a further research, in order to reveal the roles of circulating exosome RNA in metastases of osteosarcoma.

Inclusion Criteria:

• Diagnosis by biopsy: primary high-grade osteosarcoma, including conventional osteosarcoma, telangiectatic osteosarcoma, small cell osteosarcoma, high-grade surface osteosarcoma.
• Tumor located in the extremities or pelvis.
• Age 12-60 years.
• No prior history of cancer and no prior treatment elsewhere.
• No prior history of chronic diseases including autoimmune disease, chronic infection, etc. which may interfere the level of circulating exosomes.

Exclusion Criteria:

• Initial misdiagnosis confirmed by specimen of definitive surgery.
• Applying target drugs in the period of treatment which may reduce tumor derived exosomes
• withdraw from the study for any reason

patients with primary high-grade osteosarcoma aged 12-60.