RadioTherapy: Coronary Artery Calcium and Cardiovascular Risk Factors Analysis After RT or Breast Cancer

Sponsor

Centro Cardiologico Monzino (Other)

Overall Status

Recruiting

CT.gov ID

NCT05775822

Collaborator

Istituto Europeo di Oncologia (Other)

100

Enrollment

Location

Arm

26.3

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a no-profit, national, monocenter, retrospective, and prospective low-intervention study. It is a low-intervention study in terms of diagnostic additional procedure (CT scan). It is planned to recruit a maximum of 100 women diagnosed with early-stage breast cancer and treated with adjuvant breast radiotherapy from 2010 to 2017 at the European Institute of Oncology who meet all the inclusion and exclusion criteria. The aim of the Study is to analyze a population of breast cancer patients treated by adjuvant whole breast radiotherapy to identify the most important cardiovascular (CV) risk factors linked to coronary artery disease (CAD) development, in a cure-without-complications oncology strategy.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Diagnostic Test: CT scan and blood sample collection	N/A

Detailed Description

In the present study a pre-screening activity is planned, that will be conducted by the European Institute of Oncology (IEO) at the Division of Radiotherapy. It will be done to identify and select from the IEO's database about 100 women diagnosed with early-stage breast cancer and treated with adjuvant breast radiotherapy, from 2010 to 2017, and with a > 5 years clinical Follow up (FU). All patients, who present pre-specified RT treatment, in terms of radiation exposure, and radiation protocol (IORT excluded as well as previous RT treatments), will be proposed to participate in the Study. The researcher of the IEO will contact by phone each identified patient (eligible patients) to request her interest in participating in the present study and to obtain her availability to be contacted by the Investigator of Centro Cardiologico Monzino (CCM) to define all aspects and activities planned in the protocol.

Patients who meet all eligibility criteria, after signing the informed consent form, at Centro Cardioogico Monzino, will be enrolled in the study. After execution of the CT scan the patient will be contacted to discuss the CT scan result. In case of high calcium score values, patients will be performing a cardiological medical examination, ECG, and further diagnostic investigations, as clinically indicated.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

Coronary Artery Calcium and Cardiovascular Risk Factors Analysis After RT for Breast Cancer. A Gender-based Preventive Medicine Approach

Actual Study Start Date :

Mar 24, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: Single arm study After signing the informed consent form, patients who meet all eligibility criteria will be enrolled in the Study. After execution of the CT scan the patient will be contacted to discuss the CT scan result. In case of high calcium score values, patients will be performing a cardiological medical examination, ECG, and further diagnostic investigations, as clinically indicated	Diagnostic Test: CT scan and blood sample collection Each enrolled patient performs: preventive clinical cardiology assessment visit, addressed to individualized risk profile assessment and addressed to chest CT scan. a blood sampling (1 citrate tube of 5 ml) will be done the same day just the chest CT scan and analyzed locally also for future research of biomarker discovery (single sample, for those patients who agree in ICF) CT scan

Arm

Intervention/Treatment

Other: Single arm study

After signing the informed consent form, patients who meet all eligibility criteria will be enrolled in the Study. After execution of the CT scan the patient will be contacted to discuss the CT scan result. In case of high calcium score values, patients will be performing a cardiological medical examination, ECG, and further diagnostic investigations, as clinically indicated

Diagnostic Test: CT scan and blood sample collection

Each enrolled patient performs: preventive clinical cardiology assessment visit, addressed to individualized risk profile assessment and addressed to chest CT scan. a blood sampling (1 citrate tube of 5 ml) will be done the same day just the chest CT scan and analyzed locally also for future research of biomarker discovery (single sample, for those patients who agree in ICF) CT scan

Outcome Measures

Primary Outcome Measures

Primary Outcome Coronary calcium (CAC) [2 years]
Coronary calcium (CAC) assessment and its relationship with left-side or right-side breast radiation therapy and previously known cardiovascular risk factors. The quantification of CAC will be performed according to the Agatston score by multiplying the total CAC area in mm2 by a density factor ranging from 1 to 4 (1 for lesions with a density of 130-199 HU; 2 if the lesion has a density of 200-299 HU; 3 for lesions with a density of 300-399 HU; 4 for densities ≥400 HU)

Secondary Outcome Measures

Outcome 2 circulating markers [2 years]
Evaluate circulating markers, mostly related to radiation-induced oxidative stress and correlate them to previous CV events and CT data obtained. Patients will undergo a blood sample withdrawal focused on evaluation of albumin isoforms in human plasma and protein signatures. Albumin thiolation: Mercaptoalbumin (HSA-SH) and thiolated albumin (+120 ± 2 Da, Thio-HSA) will be detected and their intensities used to calculate the relative abundances. Targeted Proteomics will be performed and relative quantitation will be expressed in Normalized protein expression (NPX), Normalized Protein eXpression, is Olink's arbitrary unit which is in Log2 scale. It is calculated from Ct values and data pre-processing (normalization) is performed to minimize both intra- and inter-assay variation. NPX data allows users to identify changes for individual protein levels across their sample set, and then use this data to establish protein signatures.
Outcome 3 Incidence of CV events [2 years]
Incidence of CV events in relationship to left vs right-side breast radiation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women diagnosed with early-stage breast cancer treated with adjuvant whole breast external beam radiotherapy from 2010 to 2017;
Patients with a > 5 years clinical follow-up (FU) from diagnosis of breast cancer
Adult women/patients ≥18 years old and ≤ 60 years at time of radiation therapy;
Patients with homogeneous and standardized radiation exposure protocol (external beam radiotherapy 40 Gy in 15 fractions)
Patients who have signed the written informed consent

Exclusion Criteria:

Patients aged < 18 or > 60 years at time of radiation therapy;
Patients with bilateral breast cancer or breast cancer of unknown laterality;
Patients with a prior diagnosis of invasive cancer (apart from non-melanoma skin cancer);
Patients with known active ischemic heart disease during or before the RT period;
Patients with no definitive surgery (e.g. a biopsy only);
Patients who did not receive radiotherapy were excluded from the Study.
Patients who are currently participating in an investigational interventional study.
IORT (Intraoperative radiotherapy) and PBI (partial breast radiotherapy) excluded
Participants not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to Study procedures