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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort | Patients with locally advanced non-small cell lung cancer |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chemoradiation | Other | 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. |
| 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 |
| 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 |
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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Patients with lung cancer will be enrolled from the radiation oncology clinics at participating sites.
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| Name | Affiliation | Role |
|---|---|---|
| Bonnie Ky, MD, MSCE | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35233 | United States | ||
| The Brigham and Women's Hospital |
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.
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Plasma, Serum, and Buffy coat will be collected for planned biomarker analysis. Patients may optionally consent to have remaining blood banked for future analysis.
|
| Major Cardiovascular Events (2 Year) |
Incidence of MCE assessed by EMR review and patient interview |
| up to 24 months |
| 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 |
| 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 |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Rutger's University / Cancer Institute of New Jersey | New Brunswick | New Jersey | 08901 | United States |
| Montefiore Medical Center | The Bronx | New York | 190467 | United States |
| Lancaster General Hospital | Lancaster | Pennsylvania | 17601 | United States |
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Chester County Hospital | West Chester | Pennsylvania | 19380 | United States |
| ID | Term |
|---|---|
| D066126 | Cardiotoxicity |
| D008175 | Lung Neoplasms |
| D011832 | Radiation Injuries |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D014947 | Wounds and Injuries |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D059248 | Chemoradiotherapy |
| ID | Term |
|---|---|
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D011878 | Radiotherapy |
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