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Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated with Chemoradiation Therapy

Conditions
Lung Cancer Stage III
Lung Cancer Stage II
Cardiotoxicity
Radiation Toxicity
Interventions
Other: Chemoradiation
Registration Number
NCT04305613
Lead Sponsor
Abramson Cancer Center at Penn Medicine
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
221
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).

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
CohortChemoradiationPatients with locally advanced non-small cell lung cancer
Primary Outcome Measures
NameTimeMethod
Left Ventricular Strainup to 12 months

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

Growth Differentiation Factor 15up to 12 months

Change in GDF-15 from baseline

Coronary Flow Reserve (CFR_6 months

Change in PET/CT derived CFR from baseline

Ventricular Arterial Couplingup to 12 months

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

Cardiovascular Specific Mortality (2 Year)24 Months

Cardiovascular specific mortality assessed by EMR review

Major Cardiovascular Events (2 Year)up to 24 months

Incidence of MCE assessed by EMR review and patient interview

High Sensitivity C-Reactive Proteinup to 12 months

Change in hsCRP from baseline

Placental Growth Factorup to 12 months

Change in PIGF from baseline

Overall Survival (2 Year)24 months

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

Secondary Outcome Measures
NameTimeMethod
FACIT Dyspnea Scoreup to 5 years

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

Right Ventricular Fractional Area Change (RAC)up to 12 months

Change in echo-derived RAC from baseline

High-Sensitivity Troponin Tup to 12 months

Change in hsTnT from baseline

N-type pro Brain Natriuretic Peptideup to 12 months

Change in NTproBNP from baseline

Right Ventricular Longitudinal Strainup to 12 months

Change in echo-derived RV longitudinal strain from baseline

Circumferential Strainup to 12 months

Change in echo-derived circumferential strain from baseline

Left Ventricular Ejection Fraction (2D)up to 12 months

Change in echo-derived LVEF from baseline

Global and Regional Myocardial Blood Flow at Restup to 6 months

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

FACIT Fatigue Scoreup to 5 years

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

Godin Leisure Time Exercise Scoreup to 5 years

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

Diastolic Functionup to 12 months

Change in echo-derived measures of diastolic function from baseline

Left Ventricular Ejection Fraction (3D)up to 12 months

Change in 3D echocardiography derived LVEF from baseline

Global and Regional Myocardial Blood Flow at Stressup to 6 months

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

Left Ventricular Twist and Torsionup to 12 months

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

Valvular Diseaseup to 12 months

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

Left Ventricular systolic strain (3D)up to 12 months

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

Trial Locations

Locations (8)

Rutger's University / Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

The Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Lancaster General Hospital

🇺🇸

Lancaster, Pennsylvania, United States

Abramson Cancer Center of the University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Chester County Hospital

🇺🇸

West Chester, Pennsylvania, United States

University of Alabama

🇺🇸

Birmingham, Alabama, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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