Clinical trial NCT03235427: The CAROLE (CArdiac Related Oncologic Late Effects) Study
Official title: The CAROLE (CArdiac Related Oncologic Late Effects) Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Cardiac Disease
Cardiac Toxicity
Radiation
Radiation Therapy
Atherosclerotic Heart Disease
Cardiotoxicity
Breast Cancer
Lung Cancer
Lymphoma
Cancer
Carcinoma, Intraductal, Noninfiltrating
Keywords: Coronary
Coronary Disease
Coronary Arteriosclerosis
Heart Disease
Cardiotoxicity
Breast Cancer
Carcinoma
Coronary Vessels
Radiation
Radiation Therapy
Coronary Artery Disease
CAD
RT
CT
Cardiac toxicity
Cardiac calcium score
Chest RT
Lung Cancer
Lymphoma
Cardiac CT Scan
Coronary Artery
Coronary arteries
Cardiac Side Effect
Cardiac tissue
Cardiac
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2017-08-01
Enrollment: 201
Sex: FEMALE
Minimum age (years): 26
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women aged 18-65 at the time of breast cancer diagnosis, with a minimum of 6 years since diagnosis, with no history of heart disease prior to participants breast cancer diagnosis.

Brief summary: CAROLE seeks to evaluate the relationship between chest Radiation Therapy and coronary artery disease.

The purpose of CAROLE is to check the heart health of women who received breast cancer treatments in the past and protect them from future heart disease.

Detailed description: Background: Within the United States, there are an estimated 3.1 million women alive who have been diagnosed with invasive breast cancer, and approximately 56% of them have received radiation. Worldwide, there are 1.4 million diagnosed annually and, in 2012, it was the most commonly diagnosed cancer in women. As patients continue to live longer, cardiac dose-related toxicity has become an issue which impacts millions globally. Guidelines are sorely needed for this large at-risk population of women.

Purpose: Radiation therapy to the chest has known cardiac late effects including coronary artery disease, fibrosis, and valvular dysfunction. Unfortunately, there is no clear evidence on which radiation doses to cardiac structures cause these late toxicities. As a result, these effects are often under-recognized until after patients have become symptomatic. More than half of breast cancer patients are treated with radiation, and many receive incidental cardiac irradiation. Many of these women also receive systemic therapy which may pose additional cardiac risks. The investigators data will help to establish baseline rates of pre-clinical and clinical disease, which can be used to inform preventative guidelines that are critically needed in this at-risk population. Additionally, the investigators data will provide a better definition of the radiation dose-relationship associated with cardiac toxicity so that it will be possible to predict more accurately who is at elevated risk for iatrogenic cardiac disease.

Research Plan: This study will identify and evaluate 200 breast cancer patients treated at the investigators institution (\>6 years prior) who are at risk for treatment-related cardiac toxicity. All patients enrolled in the study will receive echocardiograms (echo), electrocardiograms (EKGs), and coronary calcium (CAC) CT scans in order to comprehensively evaluate for pre-clinical and clinical cardiac disease. Patients identified as having cardiac disease during testing will be offered referral to a cardiologist. Patients who received non-radiation treatments (chemotherapy, hormonal therapy, and/or surgery) will be compared to radiated patients to establish baseline rates of preclinical and clinical disease. Patients who received cardiotoxic systemic therapy (doxorubicin, trastuzumab, etc.) will also be evaluated in subgroup analysis. Among radiation patients, this study proposes a novel method of risk assessment, which is, to utilize a patient's stored treatment plan (from 2004-2011) and fuse it with patients current cardiac imaging to delineate an accurate dose relationship associated with clinical and pre-clinical disease. This is further described in the specific aims below:

Specific Aim 1: Identify baseline levels of clinical and pre-clinical disease in breast cancer patients.

Aim 1.1: Delineate the group of patients diagnosed and treated for breast cancer between 2004-2011, enroll health system patients with recent follow up (within 3 years).

Aim 1.2: Perform non-invasive cardiac testing (EKG, echo, CAC CT scans). Aim 1.3: Establish rates of pre-clinical and clinical disease based on pre-determined criteria.

Specific Aim 2: Create an accurate dosimetric assessment of dose to cardiac structures.

Aim 1.1: Among study patients who received radiation treatment for breast cancer, obtain stored planning CT simulation scans.

Aim 1.2: Upload CT simulation scans with dosimetric information and delineate cardiac structures at risk in order to ensure accurate and reproducible target delineation.

Aim 1.3: Fuse the CAC CT scan with the CT simulation scan to accurately assess for dose correlation between coronary calcium with the dose received.

Aim 1.4: Create a dose-relationship model for the heart and cardiac structures.

Specific Aim 3: Incorporate dosimetric cardiac risk information into the investigators institution's clinical practice, publish data, and establish updated cardiac guidelines for women who have received radiation for breast cancer.

The long-term goal of the project is to elucidate specific treatment and radiation dose-related risks, which will then be used to inform follow-up recommendations and guidelines. This project will impact the way investigators describe expected cardiac risk to patients, the way the investigators recommend follow up care, and potentially, the way the investigators prescribe treatment. At present, all patients receiving radiation for breast cancer are informed that there is a risk of cardiac late effects, however, no specific cardiac imaging or intervention is recommended other than routine medical follow up. There is little distinction given to the side of the cancer, a patient's individual anatomy, or the projected dose to the anterior heart and cardiac structures. This project will allow physicians to provide a more accurate risk profile regarding future risk of cardiac morbidity. If the study reveals a very high rate of pre-clinical atherosclerotic disease, it also may prompt more routine CAC CT screening.

Eligibility criteria: Inclusion Criteria:

* If you are a breast cancer survivor who was diagnosed between the ages of ≥ 18-65 years (now at age 26-78).
* It has been at least 6 years since you were diagnosed.
* If you did not have a diagnosis of heart disease before\* having breast cancer.

  * (\*women diagnosed with heart disease after breast cancer may still be eligible)

Exclusion Criteria:

* Patients who are unable to care for themselves or who are unable to come in for testing due to health conditions or incarceration will be rescheduled or removed in the case of chronic ineligibility. No vulnerable patient populations will be used in this study. Patients will be excluded if they have any pre-existing cardiac disease at the time of diagnosis of their breast cancer (2004-2011).
* Pregnant and nursing women are ineligible.

Primary outcomes:
measure: Multimodality Cardiology Assessment- EKG
timeFrame: 1 Year
measure: Multimodality Cardiology Assessment- Echocardiogram with Strain
timeFrame: 1 Year
measure: Multimodality Cardiology Assessment- Coronary Artery Calcium (CAC) CT
timeFrame: 1 Year
Secondary outcomes:
measure: Agatston Score
timeFrame: 1 Year
Other outcomes:
measure: Composite Assessment of Cardiac Disease
timeFrame: 1 Year
Locations:
city: Lake Success
country: United States
facility: Northwell Health
state: New York
Study officials:
affiliation: Northwell Health
name: Lucille Lee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwell Health
name: Lindsay L Puckett, MD
role: PRINCIPAL_INVESTIGATOR
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