Background
Methods/design
Objective
Study design
Endpoints
Patient selection
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Age 18 or older
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Willing and able to provide informed consent
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Eastern Cooperative Oncology Group (ECOG) performance status 0–2
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Life expectancy > 3 months
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Histologically confirmed malignancy with metastatic disease detected on imaging. A biopsy of a metastatic site is preferred, but not required
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Presence of polymetastatic disease, defined as total number of lesions greater than 10
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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
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At the discretion of the treating oncologist, it is believed that all sites of disease can be safely planned and treated
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Serious medical comorbidities precluding radiotherapy. These include interstitial lung disease in patients receiving lung radiotherapy, Chron’s disease in patients where the gastrointestinal tract will receive radiotherapy, ulcerative colitis where the bowel will receive radiotherapy, or connective tissue disorders such as lupus or scleroderma.
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For patients with liver metastases, moderate/severe liver dysfunction (Child Pugh B or C)
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Inadequate baseline bone marrow function (i.e. symptomatic anemia, neutropenia and/or thrombocytopenia which may interfere with the ability to deliver radiotherapy)
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Chronic kidney dysfunction (eGFR less than 30) where a significant dose of radiation is expected to be delivered to the kidneys.
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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, biologically effective dose calculations should be used to equate previous doses to the tolerances doses listed in Additional file 1.
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Prior treatment with systemic radiopharmaceuticals (i.e. Radium-223 or Lutetium-177)
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Any single lesion greater than 5 cm in size.
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More than 50 metastases (count excluding equivocal lesions < 5 mm in size)
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Any brain metastasis greater than 3 cm in size, or a total volume of brain metastases greater than 30 cc.
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Polymetastatic cancer limited to the brain.
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Brainstem metastases.
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Evidence of epidural disease on baseline imaging.
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Clinical or radiologic evidence of spinal cord compression.
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Dominant brain metastasis requiring surgical decompression.
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Inability to treat all sites of disease, which may include disease involving the gastrointestinal tract, mesenteric lymph nodes, or skin. This may also include diffuse/miliary metastatic disease (i.e. brain, bone, lung, liver) or other sites where it would be impossible to deliver radiotherapy at the intended dose level (i.e. lymphangitic spread, malignancy pleural effusion/ascites, leptomeningeal metastases).
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Systemic therapy use 2 weeks prior to radiotherapy delivery.
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Pregnant or lactating women.
Pre-treatment evaluation
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History and Physical examination, including prior cancer therapies.
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Restaging within 6 weeks prior to enrolment:
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Brain: CT or MRI for tumour sites with propensity for brain metastases. All patients with brain metastases (at enrolment or previously treated) require an MRI of the brain.
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Body: CT neck/chest/abdomen/pelvis and bone scan is required. This may be replaced or supplemented with an appropriate PET/CT (i.e. 18-FDG or PSMA) for tumours where uptake is expected.
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Additional imaging as clinically indicated
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Complete blood count (Hemoglobin, white blood cell count, absolute neutrophil count, platelets).
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Creatinine
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Liver function tests (AST, ALT, GGT, alkaline phosphatase), albumin, bilirubin and INR for patients with liver metastases.
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Pregnancy test for women of child-bearing age.
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Completion of FACT-G and EQ-5D-5L quality of life forms.
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Radiotherapy treatment plan has been reviewed by a physicist or radiation oncologist.
Data collection
Treatment plan
Goal | Acceptable | Not acceptable |
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PTV: ≥95% of the PTV to receive ≥95% of the prescription dose for every lesion. | GTV: ≥95% of the GTV to receive ≥95% of the prescription dose for every lesion. | 1. Failure to meet dose constraints listed in Additional file 1 2. Not being able to meet minimum “Acceptable” coverage for every lesion i.e. 3. < 90% of lesions meet the “Goal” target coverage criteria |