Clinical trial NCT03206333: Automated Quantification of Coronary Artery Calcifications on Radiotherapy Planning CTs for Cardiovascular Risk Prediction in Breast Cancer Patients: the BRAGATSTON Study
Official title: Automated Quantification of Coronary Artery Calcifications on Radiotherapy Planning CTs for Cardiovascular Risk Prediction in Breast Cancer Patients: the BRAGATSTON Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Cardiovascular Diseases
Keywords: Breast cancer
Cardiovascular diseases
Coronary artery calcium
Prediction
Risk stratification
Deep learning technique
Software development
Computed tomography scan
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: Radboud University Medical Center
First posted: 2017-07-02
Enrollment: 16000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Breast cancer patients treated with radiotherapy

Brief summary: The aim of the BRAGATSTON study is to provide a low cost tool for measuring CAC in breast cancer patients, thereby identifying patients at increased risk of CVD. Breast cancer patients and doctors can act upon this, by adapting the treatment and/or by adopting cardioprotective interventions. Hereby, the burden of CVD in breast cancer survivors can be reduced and better overall survival rates can be achieved.

Detailed description: Cardiovascular disease (CVD) is the second most common cause of death in breast cancer patients. Certain adjuvant treatments (e.g. anthracyclines, radiotherapy) increase the risk of CVD, in particular in patients with pre-existing CVD risk factors. Early identification of these patients enables targeted cardioprotective interventions, and switching to less cardiotoxic treatments. The strongest independent CVD risk factor is the presence and amount of coronary artery calcium (CAC). In clinical practice, CAC is quantified on cardiac CTs. Breast cancer patients treated with radiotherapy routinely undergo planning CTs. These inferior quality CTs may give the opportunity to routinely assess CAC.

The BRAGATSTON study is a multicenter retrospective observational cohort study (UMC Utrecht, Erasmus Medical Center and Radboudumc). The project is divided into three work packages (WP), each WP with a unique aim:

WP 1: To develop/optimize and validate the UMC Utrecht developed automated software to determine the presence and the amount of CAC (CAC score) on radiotherapy planning CT scans of breast cancer patients.

WP 2a: To evaluate the association between CAC score measured automatically on planning CT scans and the risk of incident (non-)fatal cardiovascular events in breast cancer patients.

WP 2b: To evaluate if the association as defined by work package 2a is modified by type of adjuvant treatment.

WP 2c: To evaluate the association between other candidate imaging biomarkers (e.g. calcifications in other structures like the aorta or heart valves, the amount and distribution of body fat, bone characteristics) measured (automatically) on planning CT scans and the risk of incident (non-)fatal (cardiovascular) events in breast cancer patients.

WP 3: To assess the added value of CAC score measured automatically on planning CT scans over classic cardiovascular risk factors and over treatment characteristics to predict (non-)fatal cardiovascular events in breast cancer patients.

Eligibility criteria: Inclusion Criteria:

* Breast cancer patients treated with radiotherapy in UMC Utrecht, Erasmus Medical Center or Radboudumc between 2004-16
* Planning CT scan available
* Age: ≥18 years
* Gender: both genders

Exclusion Criteria:

* Not applicable

Primary outcomes:
measure: Incident (non-)fatal (cardiovascular) diseases
timeFrame: Up to 13 years of follow-up, in hazard ratios
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: Imaging Division, University Medical Center Utrecht, Utrecht
name: Helena M. Verkooijen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht
name: Ivana Išgum, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Radiation Oncology, Erasmus Medical Center, Rotterdam
name: Luca Incrocci, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Radiation Oncology, Radboudumc, Nijmegen
name: Hanneke Meijer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gal R, van Velzen SGM, Hooning MJ, Emaus MJ, van der Leij F, Gregorowitsch ML, Blezer ELA, Gernaat SAM, Lessmann N, Sattler MGA, Leiner T, de Jong PA, Teske AJ, Verloop J, Penninkhof JJ, Vaartjes I, Meijer H, van Tol-Geerdink JJ, Pignol JP, van den Bongard DHJG, Isgum I, Verkooijen HM. Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer. JAMA Oncol. 2021 Jul 1;7(7):1024-1032. doi: 10.1001/jamaoncol.2021.1144.
citation: Emaus MJ, Isgum I, van Velzen SGM, van den Bongard HJGD, Gernaat SAM, Lessmann N, Sattler MGA, Teske AJ, Penninkhof J, Meijer H, Pignol JP, Verkooijen HM; Bragatston study group. Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer. BMJ Open. 2019 Jul 27;9(7):e028752. doi: 10.1136/bmjopen-2018-028752.