Single vs. Multiple Fraction Trial of Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastases/Progression

Inclusion Criteria:

* 1-5 current oligometastatic or oligo-progressive lesions
* Age 18 years or older
* Able to provide informed consent
* Able to complete electronic entry of patient reported outcomes and questionnaires independently or with assistance from a caregiver/family/friend/research staff using electronic methods after providing consent to email use.
* Life expectancy \> 6 months
* Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Controlled primary tumor: defined as at least 3 months since original tumor treated radically, with no progression at primary site (can be considered controlled if no evidence of the primary tumour on imaging \[e.g. primary unknown\])
* A history including ECOG performance status, performed within 6 weeks prior to enrollment
* Patient has had a CT chest, abdomen and pelvis or PET-CT within 10 weeks prior to enrollment, and within 13 weeks prior to treatment
* Patient has had a nuclear bone scan (if no positron emission tomography-computed tomography \[PET-CT\]) within 10 weeks prior to enrollment, and within 13 weeks prior to treatment
* Patient has had CT or MRI brain imaging if primary has a propensity for central nervous system metastases (if deemed appropriate by the treating investigator) within 10 weeks prior to enrollment, and within 13 weeks prior to treatment.
* For patients with known spine metastases, patient has had MRI spine imaging within 10 weeks prior to enrollment, and with 13 weeks prior to treatment.
* If solitary lung nodule for which biopsy is unsuccessful or not possible, patient has had an FDG (fluorodeoxyglucose) PET scan or CT (chest, abdomen, pelvis) and bone scan within 10 weeks prior to enrollment, and within 13 weeks prior to treatment
* If colorectal primary with rising Carcinoembryonic antigen (CEA), but equivocal imaging, patient has had an FDG PET scan within 10 weeks prior to enrollment, and within 13 weeks prior to treatment
* Patient is judged able to:

  * Maintain a stable position during therapy
  * Tolerate immobilization device(s) that may be required to deliver SABR safely
* Negative pregnancy test for People of Child-Bearing Potential (POCBP) within 4 weeks of RT start date

Exclusion Criteria:

* Uncontrolled concurrent malignant cancer
* Lesion in femoral bone requiring surgical fixation
* No chemotherapy agents (cytotoxic, or molecularly targeted agents) will be used within the period of time commencing 1 week prior to radiation, lasting until 1 week after the last fraction. See section 5.3.3 regarding this criterion.
* 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, and connective tissue disorders such as lupus or scleroderma.
* 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, similar biological effective dose calculations should be used to equate previous doses to the tolerance doses listed below. All such cases should be discussed with the local and study principal investigators (PIs).
* Current malignant pleural effusion
* Liver metastases located in the "Biliary no fly zone" defined for this trial as common biliary track, cystic duct and distal branches (1 cm) + 5 mm.
* Inability to treat all sites of oligometastatic or oligoprogressive disease (all lesions must be suitable for both single- and multi-fraction SABR)
* Presence of brain metastases as the sole site of disease
* Maximum size of 5 cm for lesions outside the brain, except:

  * Bone metastases over 5 cm may be included, if in the opinion of the local PI it can be treated safely (e.g. rib, scapula, pelvis)
* Any brain metastasis \> 3.5 cm in size or a total volume of brain metastases greater than 30 cc is excluded
* Clinical or radiologic evidence of spinal cord compression. Patients can be eligible if surgical resection has been performed
* Patients with spine instability as judged by a Spinal Instability Neoplastic Score (SINS) of \>12
* Dominant brain metastasis requiring surgical decompression
* Surgical resection of all metastases (i.e. no lesion available to be treated with SABR)
* Complete response to systemic therapy, defined as the absence of visible disease on imaging
* Pregnant or breast feeding