Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy

N/AActive Not RecruitingNCT04305613

Abramson Cancer Center at Penn Medicine221 enrolled

Overview

This observational cohort will evaluate the cardiovascular effects of chemoradiation used to treat locally advanced, non-small cell lung cancer. Patients will be enrolled prior to the start of therapy and followed during and for at least 2 years after therapy with echocardiograms, nuclear stress tests, blood sampling, and quality of life surveys.

Lung cancer is both the most common malignancy worldwide and the leading cause of cancer death in the US. While radiation therapy is highly effective for many solid tumors, thoracic radiation therapy carries a risk of cardiovascular morbidity and mortality that limits critical gains in cancer control and survival. The investigators will perform detailed cardiovascular phenotyping using biologic and imaging markers to define functional and physiologic perturbations that occur with radiation therapy. The study will provide insights into how cardiovascular risk factors and disease impact these biologic and functional changes. The investigators will also determine which radiotherapy dose-volume metrics are indicative of subclinical cardiotoxicity.

Study Type

OBSERVATIONAL

Enrollment

221

Conditions

Cardiotoxicity Lung Cancer Stage III Lung Cancer Stage II Radiation Toxicity

Interventions

ChemoradiationOTHER

Patients will be treated with definitive concurrent chemoradiation with curative intent as determined by their medical and radiation oncologists. We will consider timing of initiation and discontinuation, type, and cumulative dose of platinum based chemotherapy. We will also consider dose, duration, and type of immunotherapy. Radiation therapy will be delivered via proton or proton therapy. Our primary radiation therapy dose-volume exposures are whole heart volumetric dose. As secondary exposures, we will comprehensively define radiation therapy dose parameters to the right ventricle, entire left ventricle, left ventricle segments, coronary arteries, and mean heart dose.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * At least 18 years of age * Histologically confirmed or clinically diagnosed non-small cell lung cancer where the plan is for definitive treatment that includes radiation * Able to give written informed consent Exclusion Criteria: * Pregnant or breast-feeding * Prior treatment with anthracyclines * Radiation treatment not expected to involve any heart exposure as determined by treating provider * ECOG performance status greater than 2 * Vulnerable patients, including pregnant women and prisoners * Contraindication to rest/vasodilator stress PET/CT, including: asthma with ongoing wheezing at time of enrollment; known Mobitz Type II AV block, 3rd degree AV block, or sick sinus syndrom, without a pacemaker; systolic blood pressure less than 90mmHg; known hypersensitivity to Regadenoson and adenosine; profound sinus bradycardia (heart rate less than 40bpm).

Locations (8)

University of Alabama

Birmingham, Alabama, United States

The Brigham and Women's Hospital

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Rutger's University / Cancer Institute of New Jersey

Outcomes

Primary Outcomes

High Sensitivity C-Reactive Protein

Change in hsCRP from baseline

Time frame: up to 12 months

Growth Differentiation Factor 15

Change in GDF-15 from baseline

Time frame: up to 12 months

Placental Growth Factor

Change in PIGF from baseline

Time frame: up to 12 months

Left Ventricular Strain

Change in echo-derived measures of LV peak systolic strain (longitudinal) from baseline

Time frame: up to 12 months

Ventricular Arterial Coupling

Change in echo-derived measures of ventricular-arterial coupling (Ea/Ees) from baseline

Time frame: up to 12 months

Coronary Flow Reserve (CFR_

Change in PET/CT derived CFR from baseline

Time frame: 6 months

Overall Survival (2 Year)

All-cause mortality assessed by electronic medical record (EMR) review

Time frame: 24 months

Cardiovascular Specific Mortality (2 Year)

Cardiovascular specific mortality assessed by EMR review

Time frame: 24 Months

Major Cardiovascular Events (2 Year)

Incidence of MCE assessed by EMR review and patient interview

Time frame: up to 24 months

Data from ClinicalTrials.gov

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Secondary Outcomes

High-Sensitivity Troponin T

Change in hsTnT from baseline

Time frame: up to 12 months

N-type pro Brain Natriuretic Peptide

Change in NTproBNP from baseline

Time frame: up to 12 months

Left Ventricular Ejection Fraction (2D)

Change in echo-derived LVEF from baseline

Time frame: up to 12 months

Right Ventricular Fractional Area Change (RAC)

Change in echo-derived RAC from baseline

Time frame: up to 12 months

Right Ventricular Longitudinal Strain

Change in echo-derived RV longitudinal strain from baseline

Time frame: up to 12 months

Circumferential Strain

Change in echo-derived circumferential strain from baseline

Time frame: up to 12 months

Diastolic Function

Change in echo-derived measures of diastolic function from baseline

Time frame: up to 12 months

Valvular Disease

Change in echo-derived measures of valvular disease (degree of regurgitation or stenosis) from baseline

Time frame: up to 12 months

Left Ventricular Ejection Fraction (3D)

Change in 3D echocardiography derived LVEF from baseline

Time frame: up to 12 months

Left Ventricular systolic strain (3D)

Change in 3D echocardiography derived measures of LV systolic strain from baseline

Time frame: up to 12 months

Left Ventricular Twist and Torsion

Change in 3D echocardiography derived measures of LV twist and torsion from baseline

Time frame: up to 12 months

Global and Regional Myocardial Blood Flow at Rest

Change in PET/CT derived measures of global and regional myocardial blood flow at rest from baseline

Time frame: up to 6 months

Global and Regional Myocardial Blood Flow at Stress

Change in PET/CT derived measures of global and regional myocardial blood flow at stress from baseline

Time frame: up to 6 months

FACIT Fatigue Score

Change in FACIT Fatigue score from baseline. Score ranges from 0-52. Higher scores indicated less fatigue.

Time frame: up to 5 years

FACIT Dyspnea Score

Change in FACIT Dyspnea score from baseline. Score ranges from 0-30. Higher scores indicate more dyspnea.

Time frame: up to 5 years

Godin Leisure Time Exercise Score

Change in Godin Leisure Time Exercise Score from baseline. Higher scores indicate higher levels of physical activity.

Time frame: up to 5 years