Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy (CLARITY)

Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy: A Prospective Longitudinal Cohort

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiotoxicity; Radiation Toxicity; Lung Cancer Stage III; Lung Cancer Stage II
• Intervention / Treatment: Other: Chemoradiation

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.

• Study Type: Observational
• Enrollment (Estimated): 221

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • The Brigham and Women's Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutger's University / Cancer Institute of New Jersey
  • New York
    • The Bronx, New York, United States, 190467
      • Montefiore Medical Center
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17601
      • Lancaster General Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of The University of Pennsylvania
    • West Chester, Pennsylvania, United States, 19380
      • Chester County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with lung cancer will be enrolled from the radiation oncology clinics at participating sites.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cohort; Patients with locally advanced non-small cell lung cancer

Other: Chemoradiation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High Sensitivity C-Reactive Protein	Change in hsCRP from baseline	up to 12 months
Growth Differentiation Factor 15	Change in GDF-15 from baseline	up to 12 months
Placental Growth Factor	Change in PIGF from baseline	up to 12 months
Left Ventricular Strain	Change in echo-derived measures of LV peak systolic strain (longitudinal) from baseline	up to 12 months
Ventricular Arterial Coupling	Change in echo-derived measures of ventricular-arterial coupling (Ea/Ees) from baseline	up to 12 months
Coronary Flow Reserve (CFR_	Change in PET/CT derived CFR from baseline	6 months
Overall Survival (2 Year)	All-cause mortality assessed by electronic medical record (EMR) review	24 months
Cardiovascular Specific Mortality (2 Year)	Cardiovascular specific mortality assessed by EMR review	24 Months
Major Cardiovascular Events (2 Year)	Incidence of MCE assessed by EMR review and patient interview	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-Sensitivity Troponin T	Change in hsTnT from baseline	up to 12 months
N-type pro Brain Natriuretic Peptide	Change in NTproBNP from baseline	up to 12 months
Left Ventricular Ejection Fraction (2D)	Change in echo-derived LVEF from baseline	up to 12 months
Right Ventricular Fractional Area Change (RAC)	Change in echo-derived RAC from baseline	up to 12 months
Right Ventricular Longitudinal Strain	Change in echo-derived RV longitudinal strain from baseline	up to 12 months
Circumferential Strain	Change in echo-derived circumferential strain from baseline	up to 12 months
Diastolic Function	Change in echo-derived measures of diastolic function from baseline	up to 12 months
Valvular Disease	Change in echo-derived measures of valvular disease (degree of regurgitation or stenosis) from baseline	up to 12 months
Left Ventricular Ejection Fraction (3D)	Change in 3D echocardiography derived LVEF from baseline	up to 12 months
Left Ventricular systolic strain (3D)	Change in 3D echocardiography derived measures of LV systolic strain from baseline	up to 12 months
Left Ventricular Twist and Torsion	Change in 3D echocardiography derived measures of LV twist and torsion from baseline	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	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	up to 6 months
FACIT Fatigue Score	Change in FACIT Fatigue score from baseline. Score ranges from 0-52. Higher scores indicated less fatigue.	up to 5 years
FACIT Dyspnea Score	Change in FACIT Dyspnea score from baseline. Score ranges from 0-30. Higher scores indicate more dyspnea.	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.	up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (5 Year)	All Cause Mortality assessed by National Death Index Search performed 5 years after the last patient is enrolled.	5-8 years
Cardiovascular Specific Mortality (5 Year)	Cardiovascular Specific Mortality by National Death Index Search performed approximately 5 years after the final patient is enrolled.	5-8 Years
Major Cardiovascular Events (5 Year)	Incidence of 5-Year MCE by EMR review and patient interview	5 years
NCI Patient Reported Outcomes Common Terms and Criteria for Adverse Events (PRO-CTCAE)	Incidence of symptomatic adverse events as assessed by NCI's PRO-CTCAE	5 Years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Bonnie Ky, MD, MSCE, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: March 10, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Lung Cancer; Cardiovascular Disease; Radiation Therapy; Cardio-Oncology; Cardiovascular Risk Factors; Radiation Therapy Cardiotoxicity; Cardiovascular Phenotyping
• Additional Relevant MeSH Terms: Wounds and Injuries; Pathologic Processes; Neoplasms by Site; Neoplasms; Heart Diseases; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Pathological Conditions, Signs and Symptoms; Lung Neoplasms; Cardiovascular Diseases; Cardiotoxicity; Radiation Injuries; Therapeutics; Drug Therapy; Radiotherapy; Combined Modality Therapy; Chemoradiotherapy
• Other Study ID Numbers: UPCC 13519

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Participants may opt in to allowing data and/or banked samples to be used for future research and shared with other researchers. A detailed plan for sharing IPD will be finalized at a later date, and may depend in part on how many participants elect this option. Additional supporting information may be shared, including the study protocol and informed consent form.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No