Biologically-Adapted, Dose-Escalated Radiotherapy for the Treatment of Ewing Sarcoma, BEAR Trial

• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo blood sample collection
• Chemotherapy (Drug), also known as Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General: Given chemotherapy
• Computed Tomography (Procedure), also known as CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography: Undergo CT or PET/CT
• Conventional Radiotherapy (Procedure), also known as 2-Dimensional Conventional Radiation Therapy, 2D Conventional Radiotherapy, 2D Radiotherapy, 2D-RT, Radiation, 2D Conventional: Undergo conventional radiotherapy
• Definitive Surgical Resection (Procedure): Undergo definitive surgical resection
• Dose-escalated Radiation Therapy (Radiation), also known as Dose-escalated RT: Undergo hypofractionated or conventional radiotherapy
• Electronic Health Record Review (Other): Ancillary studies
• External Beam Radiation Therapy (Radiation), also known as Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation: Undergo definitive radiotherapy
• Hypofractionated Radiation Therapy (Radiation), also known as Hypofractionated, Hypofractionated Radiotherapy, hypofractionation, Radiation, Hypofractionated: Undergo hypofractionated radiation therapy
• Magnetic Resonance Imaging (Procedure), also known as Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI: Undergo MRI
• Positron Emission Tomography (Procedure), also known as Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT: Undergo PET/CT
• Questionnaire Administration (Other): Ancillary studies
• Radiation Therapy (Radiation), also known as Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation: Undergo hypofractionated or conventional standard radiotherapy

Primary outcomes

• Reduction in local failure for patients with large tumors (Cohort A) [Up to 2 years]: Large tumors defined as ≥ 8cm. Will be compared to the historical control of 14.3%. Local failure will be defined per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary outcomes

• Incidence of targeted, late grade 3 or greater adverse events (Cohort A) [Up to 1 year after completion of local therapy]: Assessed per RECIST version 1.1.
• Event-free survival (Cohort A) [Up to 1 year after completion of local therapy]: Event-free survival (EFS) is defined as the time from study entry to any progression of disease or recurrence of disease or death from any cause, whichever occurs first.
• Time to progression (Cohort A) [Up to 1 year after completion of local therapy]: Will be calculated descriptively, via frequencies and percentages at various timepoints of interest, including the 1-year local control rate.
• Overall survival (Cohort A) [Up to 1 year after completion of local therapy]: Overall survival (OS) is defined as the time from study entry to death from any cause, estimated using the Kaplan-Meier method.

Sex: All, ages: 2 Years to any

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
* Lansky or Karnofsky performance status ≥ 70
* Ability to provide written informed consent and complete questionnaire(s) by themselves or with assistance
* Willing to provide blood samples for correlative research purposes
* Willing to provide biopsy sample to run Mayo Complete Solid Tumor Panel if tumor size is >= 8 cm

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

  * Note: Co-enrollment on another clinical trial is allowed per the treating radiation oncologist's discretion
* Other active malignancy ≤ 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes
* Patients that have severe co-morbid systemic illness or other disease which would interfere significantly with the current treatment or measurement of outcomes
* Patients that have active uncontrolled systemic infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness or social situation that would limit study adherence
* Any of the following:

  * Pregnant patients
  * Nursing patients

• Roman O. Kowalchuk, MD, Principal investigator, Mayo Clinic in Rochester