Inclusion Criteria

• Histological confirmation of Ewing sarcoma, including both skeletal and extra-skeletal primary tumors. Patients with “Ewing-like” sarcoma may be eligible if patients are planned to be treated per Ewing treatment paradigms, as defined in this clinical trial.
• Patients of age ≥ 2 years are eligible for the study.
• Negative pregnancy test done ≤ 7 days prior to registration, for patients of childbearing potential only.
• Ability to provide written informed consent and complete questionnaire(s) by themselves or with assistance.
• Willing to provide blood samples for correlative research purposes (see Section 6.0 and 14.0).
• Co-enrollment on another clinical trial is allowed per the treating radiation oncologist’s discretion.

Exclusion Criteria

• Prior chemotherapy or radiotherapy that, in the opinion of the treating medical oncologist or radiation oncologist, is considered to interfere with the current treatment or measurement of outcomes.
• Receiving any investigational agent which would be considered as a treatment for the primary neoplasm that is considered by the investigator to interfere with the current treatment or measurement of outcomes.
• Other active malignancy ≤ 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes.
• Any of the following:
  • • Pregnant patients
    • Nursing patients
    • Patients of childbearing potential who are unwilling to employ adequate contraception

Special case

If a patient presents prior to the initiation of local therapy but after the initiation of chemotherapy, that patient can still be enrolled on the trial. In such a case, the patient must be willing provide biospecimens at all future timepoints, as denoted in Sections 4.0 and 14.0. Such a patient could still be counted towards the primary endpoint of local failure if the patient proceeds through Cohort A and characterization of unfavorable biology is completed.