Atherosclerotic Disease, Cancer, Cardiotoxicity
Conditions
Keywords
cancer, atherosclerosis, FDG, PETCT, cardiotoxicity, VEGFI, immune checkpoint inhibitor
Brief summary
The advent of immunotherapy (immune checkpoint inhibitors \[ICI\]) has been an extremely important advancement for cancer treatment in recent decades. The anti-cancer effects of these agents is profound and can lead to radiological 'disappearance' of the primary cancer and metastatic deposits. ICI are now commonly used in the treatment of multiple cancers including melanoma, kidney cancer, liver cancer and lung cancer. ICI can be used on their own or in combination with other agents such as vascular endothelial growth factor inhibitors (VEGFi) which is first line treatment for many patients. However, it has become clear that these drugs have cardiovascular side effects including high blood pressure and a reduction in the heart muscle pumping function. It is also increasingly recognised that ICIs may have a toxic effect on blood vessels resulting in an increased risk of heart attack or stroke. These side effects can have a significant impact on patients' health and can lead to withdrawal of important cancer treatment. The mechanisms by which these side effects occur are unclear and have not been well described to date. The aim of this study is to examine the effect of ICI and VEGFi, both alone and in combination, on blood vessels and to understand their effects on blood markers and heart function. This study is observational and will not require any modification of cancer therapy. This study will aim to recruit patients diagnosed with cancer who are already planned to receive ICI or VEGFi alone or in combination at the Beatson West of Scotland Oncology Centre. Patients will undergo a vascular PET-CT scan before and 6 months after starting treatment. In addition patients will undergo echocardiography and tests of the function of the small blood vessels in the fingertips with a special machine (EndoPat). Blood and urine samples will also be collected.
Interventions
DIAGNOSTIC_TESTPET/CT with 18-FDG
Study specific tests will include 18F-FDG PET/CT (specialised CT scan), electrocardiography (ECG), clinic blood pressure assessment, blood tests, urine sample, echocardiography (heart ultrasound) and tests on the fingertips (EndoPAT). Positron emission tomography with computerised tomography (PET-CT) is a scanning technique in routine clinical use. It is the gold standard method for assessing blood vessel inflammation. A small amount of radioactive sugar (18F-FDG \[18F- fluorodeoxyglucose\]) is administered intravenously 90 minutes prior to the PET-CT scan. The distribution of uptake of this tracer is seen on the subsequent PET-CT scan. The CT component of this scan allows the PET image to be precisely aligned with anatomical structures (especially large blood vessels).
Sponsors
Roche Diagnostics GmbH
University of Glasgow
NHS Greater Glasgow and Clyde
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with cancer who are planned for treatment with ICI or VEGFI, including combination therapy 2. ≥6 months predicted survival 3. Age ≥18 years
Exclusion criteria
1. Patients who are unable or unwilling to provide valid consent for the study 2. Patients with diabetes who are on oral anti-diabetic treatment or insulin at baseline 3. patients who have exposure to either immune checkpoint inhibitor or VEGF inhibitor in the 12 months before enrolment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean arterial TBRmax 18F FDG uptake | 24 weeks | Inflammatory plaque activity (meanMaxTBR)\* in patients receiving ICI/VEGFI combination therapy versus ICI alone or VEGFI alone. \*Note 'meanMaxTBR' is a PET measurement reflecting the average of the maximum 'target to background ratio \[TBR\]) where 'target' denotes regions of PET radiotracer activity) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood and urine biomarker analysis | Baseline (pre-treatment) to 24 weeks | Correlation between baseline and longitudinal changes in humoral/urinary biomarkers as potential predictors of subsequent change in inflammatory plaque activity (TBR). Analysis of blood and urine biomarkers with inflammatory plaque activity (meanMaxTBR) in patients receiving ICI (alone or in combination) vs VEGFI alone. |
| Inflammatory plaque activity (meanMaxTBR) in patients receiving ICI (alone or in combination) vs VEGFI alone. | Baseline (pre-treatment) to 24 weeks | In addition to ICI vs VEGFI vs ICI/VEGFI combination therapy, we will also compare PET activity in those who had ICI (monotherapy or combination therapy) with VEGFi monotherapy. |
| PET activity with baseline cardiovascular risk factors and imaging (echo/CT) | Baseline (pre-treatment) to 24 weeks | Correlation between baseline cardiovascular risk factors and imaging (echo/CT) findings will be examined as predictors of subsequent change in inflammatory plaque activity (TBR). |
| The effect of ICI/VEGFI upon endothelial function (EndoPAT) will be examined. | Baseline (pre-treatment) to 24 weeks | The effect of ICI/VEGFI upon endothelial function (EndoPAT) will be examined. |
| PETCT 18F FDG uptake arterial analyses | Baseline (pre-treatment) to 24 weeks | In accordance with European Association of Nuclear Medicine guidelines, in addition to TBRmax, arteries will be analysed using TBRmean (tissue to background ratio mean FDG uptake), active segment; and most diseased segment. |
Countries
United Kingdom
Outcome results
None listed