The attending radiation oncologist contoured OTX015 tumors with no margin for microscopic extension using all available clinical, radiographic, and metabolic data then expanded 5�C10 mm to account for set-up error. A variety of non-overlapping axial fields and non-coplanar fields were combined to achieve the optimal radiation distribution to tumors while minimizing radiation to surrounding non-involved organs. The estimated normal tissue tolerances from the available literature were referenced in determining radiation plans. Typically, radiation was delivered in three doses for those treated on protocol and in a ten-dose regimen for those treated off protocol. Furthermore, prospective level-1 evidence has demonstrated this approach, with or without whole brain radiotherapy, leads to 80�C90% local control of lesions. From December 2004 to June 2010, 34 patients were treated with HIGRT at all sites of active limited metastatic disease. Eleven of these patients were analyzed retrospectively, while 23 patients were included prospectively from a previously reported radiotherapy protocol for oligometastasis. For inclusion in this report, availability of at least one formalin fixed paraffin embedded tissue biopsy from the primary site or a metastatic site was also required. Patients with small volume biopsies or fine needle aspirations were excluded, as there was not enough tissue for RNA extraction. We collected paired primary and metastatic tumor samples from 5 patients, primary tumors only from 20 patients, and metastatic tumors only from 9 patients. Following radiotherapy, patients underwent physical examination and imaging at one month following HIGRT to assess initial response and then every three months subsequently for up to 41 months. Metastasis were defined based on axial imaging using CT scans of the Chest/Abdomen/ Pelvis with iodinated contrast. For brain imaging, gadolinium enhanced MRI scans was used. The modality chosen for follow-up was based on the imaging employed to initially evaluate and treat the patient����. The percentage of imaging modalities used to select and treat patients is included in Table S5c. Survival was defined as the time from the initiation of radiation treatment until death from any cause. Patients were classified into two groups based on response after completion of radiation therapy: polymetastatic patients had progression in developing more than 5 new tumors in less than 4 months from time of first metastatic progression, or progression within a body TWS119 clinical trial cavity that by definition would imply the presence of diffuse metastatic disease. In contrast, Oligometastatic patients had either no evidence of progression or insufficient rate of metastatic progression to satisfy the above criteria for polymetastases.