Circulating Exosome RNA in Lung Metastases of Primary High-Grade Osteosarcoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Pilot Study of Circulating Exosome RNA as Diagnostic and Prognostic Markers in Lung Metastases of Primary High-Grade Osteosarcoma

Conditions
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Lung Metastases, Osteosarcoma

Intervention / Treatment
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* Other: Blood samples


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| metastatic<br>For osteosarcoma patients with metastasis, collecting blood samples. | Other: Blood samples<br>* 15 ml peripheral blood<br>|
| non-metastatic<br>For osteosarcoma patients without metastasis, collecting blood samples. | Other: Blood samples<br>* 15 ml peripheral blood<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in the levels and mutations of circulating exosome RNA from patients with or without lung metastasis. | Next generation sequencing will be performed to the whole RNA sequencing. | Before the neo-adjuvant chemotherapy, before the definitive surgery procedure, every 6 months after surgery. up to 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in the classic cell signal pathway mutations of circulating exosome RNA from patients with or without lung metastasis. | Next generation sequencing will be performed to the whole RNA sequencing. | Before the neo-adjuvant chemotherapy, before the definitive surgery procedure, every 6 months after surgery. up to 3 years. | 
| Differences in the therapeutic targets mutations of circulating exosome RNA from patients with or without lung metastasis. | Next generation sequencing will be performed to the whole RNA sequencing. | Before the neo-adjuvant chemotherapy, before the definitive surgery procedure, every 6 months after surgery. up to 3 years. | 
| The correlation between circulating exosome RNA mutation levels and 3-year disease-free survival (DFS), progression-free survival (PFS), lung metastases. | Next generation sequencing will be performed to the whole RNA sequencing. | Before the neo-adjuvant chemotherapy, before the definitive surgery procedure, every 6 months after surgery. up to 3 years. | 
| The correlation between specific circulating exosome RNA mutations and 3-year disease-free survival (DFS), progression-free survival (PFS), lung metastases. | Next generation sequencing will be performed to the whole RNA sequencing. | Before the neo-adjuvant chemotherapy, before the definitive surgery procedure, every 6 months after surgery. up to 3 years. | 
| The roles of circulating exosome micro-RNA mutations on regulation of circulating exosome RNA. | Next generation sequencing will be performed to the whole RNA sequencing. | Before the neo-adjuvant chemotherapy, before the definitive surgery procedure, every 6 months after surgery. up to 3 years. | 
| The mutations of circulating exosome RNA from patients without metastasis. | Next generation sequencing will be performed to the whole RNA sequencing. | Before the neo-adjuvant chemotherapy, before the definitive surgery procedure, every 6 months after surgery. up to 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RNA profiling, Exosome, Lung Metastases, Osteosarcoma