Patients randomized to Arm 1 will undergo appropriate therapy as determined by their oncologist. These patients will either continue their current therapy or be transitioned to a new standard of care therapy at the discretion of the treating oncologist. If randomized to Arm 1, these patients may undergo palliative RT for progressive, painful lesions (a skeletal related event) at time of symptom development (not upfront palliative RT).

Systemic Therapy: Standard of care systemic therapy, including chemotherapeutics, targeted therapies, immunomodulatory agents, and hormonal therapies will be delivered at the discretion of the treating medical oncologist. Patients may receive systemic therapy concurrently and there are no restrictions on initiation of systemic agents after radiotherapy including immunotherapy and hormonal therapy, the timing of which will be determined by a consensus between the treating medical and radiation oncologists.

Patients on Arm 2 of the study will undergo selective RT to ≤ 5 high risk bone metastases defined as 1. bulkiest sites of osseous disease ≥ 2cm, 2. disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints 3. disease in long bones with1/3-2/3 cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpus, phalanges) 4. disease in junctional spine (C7-T1, T12-L1, L5-S1) &/or disease with posterior element involvement.

Radiation Therapy: Radiation therapy will be delivered according to department standards. For this protocol, total dose and dose fractionation may be delivered at the discretion of the treating radiation oncologist according to department standards. All techniques including conventional, 3D-CRT, or IMRT technique may be used. Image guidance at the time of treatment delivery to verify patient positioning may be chosen at the discretion of the treating radiation oncologist according to department standards.

Total of all reporting groups

Patients randomized to Arm 1 will undergo appropriate therapy as determined by their oncologist. These patients will either continue their current therapy or be transitioned to a new standard of care therapy at the discretion of the treating oncologist. If randomized to Arm 1, these patients may undergo palliative RT for progressive, painful lesions (a skeletal related event) at time of symptom development (not upfront palliative RT).

Systemic Therapy: Standard of care systemic therapy, including chemotherapeutics, targeted therapies, immunomodulatory agents, and hormonal therapies will be delivered at the discretion of the treating medical oncologist. Patients may receive systemic therapy concurrently and there are no restrictions on initiation of systemic agents after radiotherapy including immunotherapy and hormonal therapy, the timing of which will be determined by a consensus between the treating medical and radiation oncologists.

Patients on Arm 2 of the study will undergo selective RT to ≤ 5 high risk bone metastases defined as 1. bulkiest sites of osseous disease ≥ 2cm, 2. disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints 3. disease in long bones with1/3-2/3 cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpus, phalanges) 4. disease in junctional spine (C7-T1, T12-L1, L5-S1) &/or disease with posterior element involvement.

Radiation Therapy: Radiation therapy will be delivered according to department standards. For this protocol, total dose and dose fractionation may be delivered at the discretion of the treating radiation oncologist according to department standards. All techniques including conventional, 3D-CRT, or IMRT technique may be used. Image guidance at the time of treatment delivery to verify patient positioning may be chosen at the discretion of the treating radiation oncologist according to department standards.