Ablative Radiotherapy to Restrain Every Metastasis Safely Treatable (ARREST-2): A Randomized Phase II/III Trial

Inclusion Criteria:

* Age 18 or older
* willing and able to provide informed consent
* ECOG performance status 0-2
* Life expectancy \> or equal to 6 months
* Histologically confirmed malignancy with evidence of metastatic disease on imaging
* All sites of disease can be safely treated on a preliminary radiation plan
* \> or equal to 11 metastases (the primary tumor does not have to be controlled and can be included as a target if it can feasibly and safely be treated with SABR. If the primary tumor is treated, a minimum of 12 targets are required0 at least 11 metastases are required in addition to the primary tumor.)
* Investigations required within 12 weeks of enrollment:
* Brain: MRI is required for all patients with known untreated or previously treated brain metastases. MRI is strongly recommended for all tumor sites with a propensity to develop brian metastases.
* Body: 18-FDG PET/CT imaging is recommended, except for tumors where FDG uptake is not expected (e.g. prostate, renal cell carcinoma). PSMA-PET or choline-PET is recommended for prostate cancer. In situations where a PET scan is unavailable, or for tumors that do not take up radiotracer, a CT neck/chest/abdomen/pelvis and bone scan are required.
* Liver: For patients with liver metastases, a diagnostic or simulation MRI is required to confirm the total number of metastases.
* No plans for systemic therapy (i.e. chemotherapy, targeted agent, immunotherapy) for 3 months from the time of enrolment. Reasons may include: a break from systemic therapy is desired by the patient and medical oncologist, the patient declines next line of systemic therapy, or no further systemic therapy options are available. Exceptions include hormone therapy for breast cancer or prostate cancer, which may be continued.
* SABR or palliative radiotherapy should commence no later than 2 weeks after randomization.
* For patients with brain metastases that are going to be treated regardless of the study arm, there must be additional extracranial disease present that will be treated with SABR on Arm 2 and not treated with SABR on Arm 1.

Exclusion Criteria:

* Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients requiring thoracic radiation, Chrohn's disease in patients where the GI tract will receive radiotherapy, ulcerative colitis where the bowel will receive radiotherapy and connective tissue disorders such as lupus or scleroderma.
* For patients with liver metastases, moderate/severe liver dysfunction (Child-Pugh B or C)
* Substantial overlap with a previously treated radiation volume. Prior radiotherapy is allowed, as long as the composite plan meets dose constraints herein. For patients treated with radiation previously, biologically effective dose calculations should be used to equate previous doses to the tolerance doses listed in Appendix 1. All such cases must be discussed with the study PI.
* Inability to treat all sites of disease. Any brain metastasis \>3 cm in size or a total volume of brain metastases greater than 30 cc.
* Solitary or dominant brian metastasis requiring surgical decompression.
* Radiologic evidence of spinal cord compression.
* Disseminated disease, including leptomeningeal metastases, peritoneal metastases/carcinomatosis, malignant pleural effusion, and lymphangitis carcinomatosis.
* Pregnant or lactating women.