Liquid Biopsy in Ewing Sarcoma and Osteosarcoma As a Prognostic and Response Diagnostic: LEOPARD

Inclusion Criteria:

• For Part A, subjects must meet all of the following eligibility criteria.

• Age: ≥ 12 months of age at time of study enrollment to 50 years of age

• Diagnosis: Patients with histologic diagnosis (by institutional pathologist) ofnewly diagnosed, localized or regionally disseminated Ewing sarcoma or peripheralprimitive neuroectodermal tumor (PNET) of bone or soft tissue or; Patients withhistologic diagnosis (by institutional pathologist) of newly diagnosed, non-pelvic,localized or regionally disseminated high-grade osteosarcoma. NOTE: Staging will beassessed according to standard of care at the treating center.

• Prior Therapy:

• Patients should have only previously had a biopsy, and not had prior attempt attumor resection.

• Not yet started chemotherapy or radiation therapy OR patient has startedchemotherapy or radiation therapy, but an appropriate pre-treatment baselinesample was collected and processed for ctDNA under a local banking study inDFCI Pediatrics and is available to use for this study.

• Planned to receive chemotherapy as follows:

-- VDC/IE as per COG protocols AEWS0031, AEWS1031 or AEWS1221 (for patients withEwing sarcoma or PNET); or MAP as per COG protocol AOST0331 (for patients withosteosarcoma).

• For Part B subjects must meet all of the following eligibility criteria.

• Age: ≥ 12 months of age at time of study enrollment

• Diagnosis: Patients with histologic diagnosis (by institutional pathologist) ofnewly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET)of bone or soft tissue

• Prior Therapy:

• Patients should have had only frontline therapy as per institutional standard,and maintenance therapy if given (no relapse therapy).

• If frontline systemic therapy already completed (not including maintenance ormetastatic site radiation), therapy completed within 6 months of enrollment toPart B.

• Subjects must have a willing physician provider supporting their participationin Part B.

• For Part B, providers are eligible to receive the provider survey if they are listedas the primary provider for the patient at the study site.

Exclusion Criteria:

• For Part A, subjects must not meet any of the following exclusion criteria.

• Patients with distant metastatic disease.

• Patients with known Ewing-like sarcoma (e.g., BCOR-CCNB3 or CIC-DUX4 translocatedsmall round cell sarcomas) are not eligible.

• Patients who are enrolled with an initial diagnosis of Ewing sarcoma andsubsequently found to have Ewing-like sarcoma will be replaced. Samples obtainedprior to removal from study will be analyzed and reported descriptively. Patientswith Ewing-like tumors may continue to provide samples and clinical data until theymeet off-study criteria per protocol.

• Patients weighing < 5 kg at time of diagnosis

• Patients with a second malignant neoplasm

• Patients without detectable tumor at the time of study enrollment (ie, completetumor resection prior to study enrollment)

• Patients already receiving tumor-directed therapy at the time of study enrollmentexcept when a pre-treatment baseline sample has already been obtained under a localbanking study in DFCI Pediatrics that would be eligible for analysis under thisstudy.

• Patients with osteosarcoma with a pelvic primary tumor site Pregnancy

• For Part B, subjects must not meet any of the following exclusion criteria.

• Patients with known Ewing-like sarcoma (e.g., BCOR-CCNB3 or CIC-DUX4 translocatedsmall round cell sarcomas) are not eligible.

• Samples obtained prior to removal from study will be analyzed and reporteddescriptively. Patients with Ewing-like tumors may continue to provide samples andclinical data until they meet off-study criteria per protocol

• Patients weighing < 5 kg at time of enrollment

• Patients diagnosed with relapsed disease and/or having started therapy directed atdisease relapse

• Pregnancy

• Resides outside of the United States

• For Part B, providers at non-study centers will not be eligible to receive theprovider survey.