Serial PET MPI in Patients Undergoing Cancer Treatment

Study Overview
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Brief Summary
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This study aims to evaluate the effects of cardiotoxic cancer therapies on myocardial blood flow (MBF) and perfusion in a prospective sample of VA patients.

Detailed Description
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Up to 60 patients who will be newly initiating chemotherapy are going to be prospectively evaluated using PET myocardial perfusion imaging (MPI) for chemotherapy-induced cardiotoxicity by quantifying MBF and perfusion. Patients will be grouped into 3 categories: Patients undergoing chemotherapy with anthracycline containing regimen. Patients undergoing chemotherapy with VEGF inhibitor containing regimen. Patients undergoing chemotherapy with immune check point inhibitor containing regimen. Patients will undergo PET MPI at 3 different time points: Baseline PET MPI within 1 month prior to initiation of the chemotherapy regimen. PET MPI at the middle of the chemotherapy regimen. PET MPI within 1 month following completion of the chemotherapy regimen. For PET MPI, the investigators will evaluate for abnormalities such as new perfusion defects, decreases in stress myocardial blood flows and decreases in myocardial flow reserves. All study patients will also be analyzed using the following tests: Echocardiogram with strain analysis within +/- 1 week of each PET MPI Serology - high sensitivity troponin, cardiac C-reactive protein (CRP), brain-type natriuretic peptide (BNP), fasting lipid panel, complete metabolic panel, and complete blood count within +/- 1 week of each PET MPI study. 12-lead ECG with each PET MPI study.

Official Title
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Prospective Evaluation of Chemotherapy-Induced Cardiotoxicity by Serial PET Myocardial Perfusion and Blood Flow Assessment - the PRECISION Trial

Conditions
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Cancer, Chemotherapeutic Toxicity, Coronary Artery Disease, Coronary Microvascular Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veterans Affairs oncology patients who will be initiating chemotherapy Ability to give consent Exclusion Criteria: Prior chemotherapy Prior coronary revascularization (percutaneous coronary intervention, coronary artery bypass grafting) Anyone with previous invasive or CT (computed tomography) angiogram demonstrating any lesion ≥ 50% stenosis Known cardiomyopathy defined as rest ejection fraction < 50% History of heart and/or another organ transplant Pregnancy or breast-feeding status

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Anthracycline<br>Patients undergoing chemotherapy with an anthracycline-containing regimen. | |
| VEGF Inhibitor<br>Patients undergoing chemotherapy with a vascular endothelial growth factor (VEGF) inhibitor-containing regimen. | |
| Immune Checkpoint Inhibitor<br>Patients undergoing chemotherapy with an immune check point inhibitor-containing regimen. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET myocardial perfusion imaging (MPI). | Change from baseline in number of patients with perfusion defects measured as % total perfusion deficit (TPD) of the left ventricular myocardium by PET | Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months) | 
| PET myocardial blood flow (MBF) measurement. | Change from baseline in number of patients with myocardial blood flow abnormalities measured as stress myocardial blood flow (SMBF) values < 2 mL/min/g of left ventricular myocardium by PET | Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transthoracic echocardiography (TTE) global left ventricular systolic function. | Change from baseline in number of patients with global systolic dysfunction measured as % left ventricular ejection fraction by TTE. | Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months) | 
| Transthoracic echocardiography (TTE) focal left ventricular systolic function. | Change from baseline in number of patients with focal systolic dysfunction measured as % left ventricular global longitudinal strain by TTE. | Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months) | 
| Transthoracic echocardiography (TTE) focal left atrial systolic function. | Change from baseline in number of patients with focal systolic dysfunction measured as % left atrial strain by TTE. | Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months) | 
| Electrocardiogram (ECG) findings. | Change from baseline in number of patients with any of the following ECG changes: new T-wave inversions new ST-segment deviations >/= 1mm new left bundle branch block | Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months) | 
| Metabolic or cardiac function abnormalities as determined by blood work findings | Change from baseline in number of patients with changes in the values of serological tests indicative of metabolic or cardiac function abnormalities including one or more of the following: high sensitivity troponin (ng/L) cardiac C-reactive protein (mg/L) brain-type natriuretic peptide (pg/mL) fasting lipid panel: total cholesterol (mg/dL), low-density lipoprotein cholesterol (mg/dL), high-density lipoprotein cholesterol (mg/dL), triglycerides (mg/dL) complete metabolic panel: total protein (g/dL), albumin (g/dL), total bilirubin (mg/dL), direct bilirubin (mg/dL), aspartate aminotransferase (IU/L), alanine transaminase (IU/L), alkaline phosphatase (IU/L), sodium (mmol/L), potassium (mmol/L), chloride (mmol/L), bicarbonate (mmol/L), blood urea nitrogen (mg/dL), creatinine (mg/dL), glucose (mg/dL) complete blood count: white blood cell count (k/uL), hemoglobin (g/dL), hematocrit (%), platelet (k/uL) | Baseline (within 1 month prior to the initiation of cancer treatment), during cancer treatment (estimated at 1-6 months), and within 1 month post-cancer treatment completion (approximately 2-9 months) |