Stereotactic ablative radiotherapy (SABR) is a new radiation treatment that delivers high-dose, precise radiation to small areas in the body. This new technique can potentially allow radiation treatments to be focused more precisely, and be delivered more accurately than with older treatments. This improvement could help by reducing side effects overall (through radiation exposure to a smaller area of the body over a shorter time period), and by improving the chance of controlling the cancer by more precisely treating the cancer and by giving higher doses of radiation. SABR is considered a standard treatment for some lung cancers, and selected cancers that have spread to the brain. Ongoing studies are evaluating the use of SABR for treating people with up to 10 sites of cancer in the body, but its safety and value for treating patients with poly-metastatic cancer (more than 10 sites of cancer) is not yet known.

The purpose of this study is to determine the safety of using SABR to treat people with poly-metastatic disease. To our knowledge, this is the first time that SABR will be tested in people who have poly-metastatic disease.

Inclusion Criteria:

• Age 18 or older

• Willing and able to provide informed consent

• ECOG 0-2

• Life expectancy greater than 3 months

• Histologically confirmed malignancy with metastatic disease detected on imaging. A biopsy of a metastatic site is preferred, but not required.

• Staging/Re-staging within 6 weeks prior to enrollment:

  • Brain: Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) for tumor sites with propensity for brain metastasis. All patients with brain metastases (at enrollment or previously treated) require an MRI of the brain.
  • Body: CT neck/chest/abdomen/pelvis and bone scan required. This may be replaced with a Positron Emission Tomography (PET)/CT (18-Fluorodeoxyglucose [FDG] or Prostate Specific Membrane Antigen [PSMA]) except for tumors where FDG uptake is not expected.
  • Spine: MRI of the spine is not mandatory for enrollment.

• Presence of poly-metastatic disease, defined as total number of targets greater than 10

• No standard of care systemic therapy option exists for the patient, the patient refuses further standard systemic therapy, or there is no intent to deliver systemic therapy for 3 months after enrollment.

• At the discretion of the treating oncologist, it is believed that all sites of disease can be safely treated for enrollment on study.

Exclusion Criteria:

• Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Crohn's disease in patients where the Gastrointestinal (GI) tract will receive radiotherapy, ulcerative colitis where the bowel will receive radiotherapy or connective tissue disorders such as lupus or scleroderma.

• For patients with liver metastases, moderate/severe liver dysfunction

• Inadequate baseline bone marrow function (i.e. symptomatic anemia, neutropenia and/or thrombocytopenia which may interfere with the ability to deliver radiation).

• Chronic kidney dysfunction Estimated Glomerular Filtration Rate (eGFR) less than 30 where a significant dose of radiotherapy is expected to be delivered to the kidney.

• Substantial overlap with a previously treated radiation volume. Prior radiotherapy in general is allowed, as long as the composite plan meets dose constraints herein. For patients treated with radiation previously, biological effective dose calculations should be used to equate previous doses to the tolerance doses.

• Prior treatment with systemic radiopharmaceuticals (i.e. Radium 223 or Lutetium 177)

• More than 50 metastases (count excluding equivocal lesions less than 5mm in size)

• Any single metastasis greater than 5 cm in size. This is a firm cut-off.

• Any brain metastasis greater than 3 cm in size or a total volume of brain metastases greater than 30 cc. This is a firm cut-off.

• Central Nervous System (CNS) only disease

• Metastasis in the brainstem.

• Inability to treat all sites of disease, which may include:

  • Disease involving any of the following: GI tract (including esophagus, stomach, small or large bowel), mesenteric lymph nodes, and/or skin
  • Diffuse or "miliary" metastatic disease of brain, bone, lung, liver or other sites (i.e. lymphangitic spread, malignant pleural effusion/ascites, peritoneal disease, leptomeningeal metastases) where it would be impossible to deliver radiotherapy at the intended dose level

• Any evidence of epidural disease on any baseline imaging.

• Clinical or radiologic evidence of spinal cord compression.

• Dominant brain metastasis requiring surgical decompression.

• Patients treated with prior systemic therapy are eligible for this study, however, systemic therapy agents that are cytotoxic, immunotherapeutic, or molecularly targeted agents are NOT allowed within the period of time commencing 2 weeks prior to radiation. Patients on conventional hormone therapy with anti-estrogen therapy (including but not limited to tamoxifen, letrozole, anastrozole, Luteinizing Hormone-Releasing Hormone [LHRH] agonists or antagonists) or anti-testosterone therapy (including but not limited to LHRH agonists or antagonists, direct anti-androgens like bicalutamide, apalutamide or steroid synthesis inhibitors like abiraterone) may continue this medication. No systemic therapy may be planned to initiate within 6 weeks after completion of radiotherapy.

• Pregnant or lactating women.