Is Radiation-before-pathology a Feasible Approach in the Palliative Oncology Setting? A Pragmatic Clinical Trial

Study Overview
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Brief Summary
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When a doctor suspects cancer, often a biopsy is taken for testing to confirm if cancer is present. Usually, doctors would wait for the results of a biopsy before delivering radiation, but this may lead to a patient having to wait for a treatment that he or she urgently needs. With long wait times for biopsies in Canada, this may lead to symptoms and risks of complications from cancer in the meantime. Therefore, this study is being done to answer the following question: Is it safe and feasible to deliver radiation before obtaining a biopsy in a carefully selected group of patients who urgently need radiation treatment.

Official Title
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Is Radiation-before-pathology a Feasible Approach in the Palliative Oncology Setting? A Pragmatic Clinical Trial (RT-NOW)

Conditions
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Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Willing to provide informed consent Palliative treatment intent: either metastatic or incurable locally advanced disease Tissue diagnosis is not required for determination of dose/fractionation scheme Recent cross-sectional imaging [for example - Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission Tomography/Computed Tomography (PET/CT)] of the area to be treated, done within the past 3 months Treating physician considers the pre-test probability of cancer greater than 95 percent based on clinical judgement and radiological findings. The patient has at least 1 site of cancer amenable to biopsy As per standard practices, if the radiation oncologist will be radiating the only site available to biopsy, they should proceed with caution. Participants should only be enrolled on trial if the risk of harm from delaying Radiation Therapy (RT) significantly outweighs the risks of possible non-diagnostic tissue. If the participant may potentially be eligible for systemic therapy, the treating radiation oncologist should consult a medical oncologist for an opinion regarding the risks of non-diagnostic molecular testing. The weighing of these priorities should be thoroughly discussed with the participant and the discussion should be documented. Reasons for radiating a participant with a single lesion prior to biopsy include: Spinal cord compression (actual or impending) and inoperable Brain metastasis with significant symptoms or neurologic deficits and inoperable Other lesions causing neurologic deficit Pulmonary lesion causing or threatening lung obstruction Uncontrolled bleeding (including hemoptysis and hematuria) Superior vena cava obstruction (actual or impending) Limited upside to molecular testing, as determined by the medical oncologist (for example - participant unfit for available systemic therapies, limited options for systemic therapy) Radiation is considered urgent (for example - participant should receive radiation prior to biopsy date) o Urgent indications may include but are not limited to the reasons listed previously, as well as the following: Painful metastases or primary lesion not adequately responding to analgesia Symptomatic brain metastases Bleeding Impending pathologic fracture Exclusion Criteria: Participant is potentially eligible for curative treatment Clinical suspicion of lymphoma o Some features may be suggestive of lymphoma, including fever or night sweats (for example - B symptoms excluding weight loss), or imaging showing well-defined, homogenous lymphadenopathy. These findings are not exclusion criteria specifically, but should be considered by the clinician in formulating their differential diagnosis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Inappropriate Use of Radiation Therapy in Participants with Urgent Indications Treated Prior to Biopsy Results | The percentage of participants in whom management would have differed, based on the final pathology, if the pathology had been known prior to radiation therapy. Inappropriate use of radiation therapy is defined as: If a non-cancerous process was treated, Or, the use of radiation therapy was inappropriate in hindsight (for example, the participant would have clearly been better treated with alternative options). | 2 weeks after biopsy results | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological Diagnostic Accuracy | Histological diagnostic accuracy is defined as the percentage of biopsies that yielded a histological diagnosis. This will include a comparison of diagnostic yield between biopsies done at radiated vs. non-radiated sites. | 2 weeks after biopsy results | 
| Molecular Testing Accuracy | Molecular testing accuracy is defined as the percentage of biopsies that yielded enough viable tissue for molecular testing/diagnosis. | 2 weeks after biopsy results | 
| Number of Biopsy Attempts Required |  | 2 weeks after biopsy | 
| Biopsy Complication Rates |  | 2 weeks after biopsy | 
| Time from Enrollment to First Fraction of Radiation Therapy |  | Within 1 year after enrollment | 
| Time from Enrollment to Biopsy |  | Within 1 year after enrollment | 
| Evidence of Radiation Effect in Biopsy |  | 2 weeks after biopsy results | 
| Overall Survival |  | 1 year after enrollment | 
| Edmonton Symptom Assessment System Revised Scores | Participants will rate their symptoms on a scale of 1 to 10, 0 being the best and 10 being the worst. Examples of symptoms included in the Edmonton Symptom Assessment System revised are pain, tiredness, nausea, appetite, depression, and so on. | 2 weeks after radiation therapy of 2 weeks after biopsy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palliative Irradiation, Biopsy, Radiation Therapy, Pathology