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Observational prospective cohort study designed to assess the mechanisms of fluoropyrimidine induced cardiovascular toxicity.
Fluoropyrimidine (5-FU and Capecitabine) based chemotherapy regimens form the cornerstone of treatments for gastrointestinal (GI) cancers. Fluoropyrimidines however, are associated with the development of cardiovascular toxicity which can take on different forms including chest pain, myocardial infarction, arrhythmias, heart failure and sudden death. The underlying mechanisms of cardiovascular toxicity are not fully understood.
The investigators will use quantitative cardiovascular magnetic resonance perfusion imaging, CT coronary angiography, extra-cardiac vascular assessments and serum cardiac biomarkers to improve insights into the pathophysiology of fluoropyrimidine cardiotoxicity. All enrolled participants in this two centre study will have GI cancers requiring treatment with fluoropyrimidine chemotherapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Stable patients with gastrointestinal malignancies will be recruited to this 3 timepoint study prior to initiation of fluoropyrimidine chemotherapy. All investigations will be performed at baseline, at the end of cycle 1 and 4-6 weeks post completion of treatment. |
| |
| Cohort 2 | Patients with gastrointestinal malignancies presenting to hospital with acute symptoms of fluoropyrimidine cardiotoxicity. All investigations will be performed during the acute presentation and the second visit will be performed 4-6 weeks post completion of treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cardiovascular magnetic resonance with stress perfusion | Diagnostic Test | Cardiac MRI scan to assess changes in left ventricular function, parametric mapping, strain and myocardial blood flow. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in myocardial blood flow from baseline with adenosine stress assessed by quantitative perfusion cardiac MRI | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in left ventricular ejection fraction from baseline | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment | 6 months |
| Change in left ventricular extracellular volume from baseline |
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Inclusion Criteria:
Exclusion Criteria:
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Adult patients with gastrointestinal malignancies being treated with a fluoropyrimidine based chemotherapy regimen.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Aderonke Abiodun, MBChB | Contact | 02073777000 | aderonketemilade.abiodun@nhs.net |
| Name | Affiliation | Role |
|---|---|---|
| Charlotte Manisty, PhD | UCL | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St Bartholomews Hospital | Recruiting | London | EC1A 7BE | United Kingdom |
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| CT coronary angiography | Diagnostic Test | CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease |
|
| Retinal OCT angiography | Diagnostic Test | Retinal OCTa to assess changes in retinal vasculature. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment. |
|
| Sublingual microscopy (GlycoCheck) | Diagnostic Test | To determine changes in sublingual microvascular health. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment. |
|
| Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP) | Diagnostic Test | Performed to assess for myocardial injury. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment. |
|
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
| 6 months |
| Change in left ventricular global longitudinal strain from baseline | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment | 6 months |
| Change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment | 6 months |
| Change in high sensitivity troponin T | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment | 6 months |
| Change in sublingual perfused boundary region | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment | 6 months |
| Change in sublingual capillary density | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment | 6 months |
| Change in retinal vessel density | Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment | 6 months |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D066126 | Cardiotoxicity |
| D009369 | Neoplasms |
| D015179 | Colorectal Neoplasms |
| D004938 | Esophageal Neoplasms |
| D013274 | Stomach Neoplasms |
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006258 | Head and Neck Neoplasms |
| D004935 | Esophageal Diseases |
| D013272 | Stomach Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
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