Background
Methods/design
Objectives
Primary endpoint
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Overall Survival
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Defined as time from randomization to death from any cause
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Secondary endpoints
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Quality of life
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Assessed with the Functional Assessment of Cancer Therapy: General (FACT-G)
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Toxicity
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Assessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4 for each organ treated (e.g. liver, lung, bone)]
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Progression-free survival
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Time from randomization to disease progression at any site or death
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Lesional control rate
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Number of cycles of further chemotherapy/systemic therapy
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Inclusion criteria
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Age 18 or older
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Willing to provide informed consent
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Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
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ECOG performance status 0-1
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Controlled primary tumor
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defined as: at least 3 months since original tumor treated definitively, with no progression at primary site
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All sites of disease can be safely treated based on criteria below
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Maximum 3 metastases in any single organ system (i.e. lung, liver, brain, bone), and the total number of metastases must be 5 or less. For example, a patient with two liver metastases and two lung metastases is eligible.
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Life expectancy >6 months
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Not a candidate for surgical resection at all sites: surgery to all sites not recommended by multidisciplinary team, or unfit or declining surgery
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Prior chemotherapy allowed but no chemotherapy (cytotoxic or molecularly targeted agents) therapy 4 weeks prior to first fraction of radiotherapy, during radiotherapy, or for two weeks after last fraction. Hormonal therapy is allowed.
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Patients with metastases that have been previously treated (e.g. prior resection, RFA or radiotherapy):
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○ If that previously treated metastasis is controlled on imaging, the patient is eligible for this study and that site does not need treatment
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○ If that previously treated metastasis is NOT controlled on imaging:
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If the previous treatment was surgery, the patient is eligible if that site can be treated by SABR
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If the previous treatment was radiotherapy or RFA, the patient is ineligibile.
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Patient presented at multidisciplinary tumor board or radiotherapy departmental quality-assurance rounds, with consensus opinion that entry into the study is appropriate.
Exclusion criteria
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Serious medical comorbidities precluding radiotherapy
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Bone metastasis in a femoral bone
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Patients with 1-3 brain metastasis and no disease elsewhere (these patients should not be randomized but treated with stereotactic radiotherapy as per results of randomized trials)
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Prior radiotherapy to a site requiring treatment
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Complete response to first-line chemotherapy (i.e. no measurable target for SABR)
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Malignant pleural effusion
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Inability to treat all sites of active disease
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Clinical or radiologic evidence of spinal cord compression OR tumor within 3 mm of spinal cord on MRI.
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Dominant brain metastasis requiring surgical decompression
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Pregnant or lactating women
Evaluation and randomization
Interventions
Arm 1
Arm 2
Tumor Location | Description | Total Dose (Gy) | Number of fractions | Dose per fraction (Gy) | Frequency |
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Lung
| Tumors 3 cm or less surrounded by lung parenchyma | 54 | 3 | 18 | Every second day |
Abutting chest wall or >3 cm | 55 | 5 | 11 | Every second day | |
Within 2 cm of mediastinum or brachial plexus | 60 | 8* | 7.5 | Every second day | |
Bone
| Any bone except femur | 35 Gy | 5 | 7 | Daily |
Vertebral body: additional options | 16-20 Gy OR
| 1 | 16-20 | Single dose | |
30 Gy | 3 | 10 | Every second day | ||
Brain Metastases
| If whole brain treated, then simultaneous boost to each lesion | 40 Gy to metastases 20 Gy whole brain (optional) | 5 | 8 Gy to lesion 4 Gy WBRT | Daily |
Liver
| LRCP site: Dose is based on calculated normal tissue probability of <5% | Every second day | |||
Other sites | 45-60 | 3-8 | 7.5-15 | Every second day | |
Adrenal
| 60 Gy | 8 | 7.5 | Every second day |
Quality assurance (Arm 2)
Before Treatment | Years 3-5 | Years 3-5 | ||
---|---|---|---|---|
Every 3 months | Month 3, 6, 12, 18 and 24 | Every 6 months | ||
History and Physical | X | X | X | |
Baseline staging investigations (see text) | X | |||
CT head, chest, abdomen, pelvis | X | X | ||
Bone Scan | X | X | ||
Toxicity Scoring | X | X | ||
FACT-G QOL scoring | X | X | X |