Cardiotoxicity, Lung Cancer Stage II, Lung Cancer Stage III, Radiation Toxicity
Conditions
Keywords
Radiation Therapy Cardiotoxicity, Cardiovascular Risk Factors, Lung Cancer, Cardiovascular Phenotyping, Radiation Therapy, Cardiovascular Disease, Cardio-Oncology
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.
Interventions
OTHERChemoradiation
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.
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (2 Year) | 24 months | All-cause mortality assessed by electronic medical record (EMR) review |
| Major Cardiovascular Events (2 Year) | up to 24 months | Incidence of MCE assessed by EMR review and patient interview |
| Coronary Flow Reserve (CFR_ | 6 months | Change in PET/CT derived CFR from baseline |
| Cardiovascular Specific Mortality (2 Year) | 24 Months | Cardiovascular specific mortality assessed by EMR review |
| High Sensitivity C-Reactive Protein | up to 12 months | Change in hsCRP from baseline |
| Growth Differentiation Factor 15 | up to 12 months | Change in GDF-15 from baseline |
| Placental Growth Factor | up to 12 months | Change in PIGF from baseline |
| Left Ventricular Strain | up to 12 months | Change in echo-derived measures of LV peak systolic strain (longitudinal) from baseline |
| Ventricular Arterial Coupling | up to 12 months | Change in echo-derived measures of ventricular-arterial coupling (Ea/Ees) from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction (3D) | up to 12 months | Change in 3D echocardiography derived LVEF from baseline |
| Left Ventricular systolic strain (3D) | up to 12 months | Change in 3D echocardiography derived measures of LV systolic strain from baseline |
| Global and Regional Myocardial Blood Flow at Rest | up to 6 months | Change in PET/CT derived measures of global and regional myocardial blood flow at rest from baseline |
| Global and Regional Myocardial Blood Flow at Stress | up to 6 months | Change in PET/CT derived measures of global and regional myocardial blood flow at stress from baseline |
| FACIT Fatigue Score | up to 5 years | Change in FACIT Fatigue score from baseline. Score ranges from 0-52. Higher scores indicated less fatigue. |
| FACIT Dyspnea Score | up to 5 years | Change in FACIT Dyspnea score from baseline. Score ranges from 0-30. Higher scores indicate more dyspnea. |
| Godin Leisure Time Exercise Score | up to 5 years | Change in Godin Leisure Time Exercise Score from baseline. Higher scores indicate higher levels of physical activity. |
| Left Ventricular Twist and Torsion | up to 12 months | Change in 3D echocardiography derived measures of LV twist and torsion from baseline |
| High-Sensitivity Troponin T | up to 12 months | Change in hsTnT from baseline |
| N-type pro Brain Natriuretic Peptide | up to 12 months | Change in NTproBNP from baseline |
| Left Ventricular Ejection Fraction (2D) | up to 12 months | Change in echo-derived LVEF from baseline |
| Right Ventricular Fractional Area Change (RAC) | up to 12 months | Change in echo-derived RAC from baseline |
| Right Ventricular Longitudinal Strain | up to 12 months | Change in echo-derived RV longitudinal strain from baseline |
| Circumferential Strain | up to 12 months | Change in echo-derived circumferential strain from baseline |
| Diastolic Function | up to 12 months | Change in echo-derived measures of diastolic function from baseline |
| Valvular Disease | up to 12 months | Change in echo-derived measures of valvular disease (degree of regurgitation or stenosis) from baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (5 Year) | 5-8 years | All Cause Mortality assessed by National Death Index Search performed 5 years after the last patient is enrolled. |
| NCI Patient Reported Outcomes Common Terms and Criteria for Adverse Events (PRO-CTCAE) | 5 Years | Incidence of symptomatic adverse events as assessed by NCI's PRO-CTCAE |
| Major Cardiovascular Events (5 Year) | 5 years | Incidence of 5-Year MCE by EMR review and patient interview |
| Cardiovascular Specific Mortality (5 Year) | 5-8 Years | Cardiovascular Specific Mortality by National Death Index Search performed approximately 5 years after the final patient is enrolled. |
Countries
United States
Outcome results
None listed