Cardiovascular Injury and Cardiac Fitness in Locally Advanced Non-Small Cell Lung Cancer Patients Receiving Model Based Personalized Chemoradiation

Study Overview
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Brief Summary
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This study assesses cardiovascular injury and cardiac fitness in patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (locally advanced) receiving model based personalized chemoradiation. The goal of this study is to learn more about the risk of developing heart disease as a result of chemoradiation treatment for lung cancer. Researchers also want to learn if the risk can be reduced by using a patient's individual risk profile to guide cancer treatment and help protect the heart.

Detailed Description
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PRIMARY OBJECTIVE: I. To longitudinally assess cardiac injury (serum biomarkers, and grade >= 2 cardiac events), and overall cardiac fitness (6-minute-walk test) in locally advanced (LA)-non-small cell lung cancer (NSCLC) patients receiving chemoradiation. OUTLINE: Patients undergo single photon emission computed tomography (SPECT)/computed tomography (CT) with stress test and echocardiogram with strain before radiation therapy (RT), 6-8 weeks and 12 months after completion of RT. Patients also participate in 6 minute walk test (MWT) before RT, 2-3 and 6-7 weeks during RT, then 6-8 weeks, 4-6 months and 12 months after completion of RT. Patients undergo blood sample collection and complete questionnaires over 3-5 minutes before RT, 2-3, 4-5, 6-7 weeks after the initiation of RT, then at 3, 6, 12, and 24 months after completion of RT. After completion of study treatment, patients are followed up annually for up to 10 years.

Official Title
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Longitudinal Assessment of Cardiovascular Injury and Cardiac Fitness in LA-NSCLC Patients Receiving Model Based Personalized Chemoradiation - an Adaptive Cohort Registration Study

Conditions
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Locally Advanced Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8

Intervention / Treatment
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* Procedure: 6 Minute Walk Functional Test
* Procedure: Biospecimen Collection
* Procedure: Computed Tomography
* Procedure: Echocardiography
* Procedure: Exercise Cardiac Stress Test
* Other: Questionnaire Administration
* Procedure: Single Photon Emission Computed Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with histologic diagnosis of non-small cell lung cancer The recommended treatment is thoracic radiation therapy combined with concurrent systemic therapy (chemotherapy and/or immunotherapy) with or without neoadjuvant and/or adjuvant systemic therapy (chemotherapy, immunotherapy, targeted therapy) >= 18 years of age Karnofsky performance status (KPS) >= 70 Willing and able to sign informed consents Able and willing to perform 6minute walking test Able and willing to preform required cardiac imaging examinations Exclusion Criteria: Unable or unwilling to give written informed consent Previous history of RT to the thorax Any contraindication for cardiac imaging Pregnant or breast-feeding Renal failure necessitating dialysis Unable to perform protocol tests Contraindication for any protocol tests

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard Treatment Plan (Cohort One)<br>Patients undergo SPECT/CT with stress test and echocardiogram with strain before RT, 6-8 weeks and 12 months after completion of RT. Patients also participate in 6 MWT before RT, 2-3 and 6-7 weeks during RT, then 6-8 weeks, 4-6 months and 12 months after completion of RT. Patients undergo blood sample collection and complete questionnaires over 3-5 minutes before RT, 2-3, 4-5, 6-7 weeks after the initiation of RT, then at 3, 6, 12, and 24 months after completion of RT. | Procedure: 6 Minute Walk Functional Test<br>* Participate in 6 MWT<br>* Other names: SIXMW1;Procedure: Biospecimen Collection<br>* Undergo blood and urine sample collection<br>Procedure: Computed Tomography<br>* Undergo SPECT/CT<br>* Other names: tomography;Procedure: Echocardiography<br>* Undergo echocardiogram<br>* Other names: ECHO_TEST;Procedure: Exercise Cardiac Stress Test<br>* Undergo stress test<br>* Other names: Exercise Stress Test;Other: Questionnaire Administration<br>* Complete questionnaires<br>Procedure: Single Photon Emission Computed Tomography<br>* Undergo SPECT/CT<br>* Other names: Tomography, Emission-Computed, Single-Photon;|
| Experimental: Model Based Personalized Treatment Plan (Cohort Two)<br>Patients undergo SPECT/CT with stress test and echocardiogram with strain before RT, 6-8 weeks and 12 months after completion of RT. Patients also participate in 6 MWT before RT, 2-3 and 6-7 weeks during RT, then 6-8 weeks, 4-6 months and 12 months after completion of RT. Patients undergo blood sample collection and complete questionnaires over 3-5 minutes before RT, 2-3, 4-5, 6-7 weeks after the initiation of RT, then at 3, 6, 12, and 24 months after completion of RT. | Procedure: 6 Minute Walk Functional Test<br>* Participate in 6 MWT<br>* Other names: SIXMW1;Procedure: Biospecimen Collection<br>* Undergo blood and urine sample collection<br>Procedure: Computed Tomography<br>* Undergo SPECT/CT<br>* Other names: tomography;Procedure: Echocardiography<br>* Undergo echocardiogram<br>* Other names: ECHO_TEST;Procedure: Exercise Cardiac Stress Test<br>* Undergo stress test<br>* Other names: Exercise Stress Test;Other: Questionnaire Administration<br>* Complete questionnaires<br>Procedure: Single Photon Emission Computed Tomography<br>* Undergo SPECT/CT<br>* Other names: Tomography, Emission-Computed, Single-Photon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in level of hs-TnT >= 5ng/L | Baseline up to end or chemoradiation (CRT) | up to 24 months | 
| Incidence of grade >= 2 cardiovascular events | Defined by Common Terminology Criteria for Adverse Events version 5.0. | Within 12-month of completion of CRT] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall cardiac fitness | Assessed using 6 minute walk test. | Up to 24 months after CRT | 
| EuroQol 5 Dimension 5 Level: Patient reported outcomes | Score Range 0-100 (0) Worst health and (100) best health Level 1- No complaints Level 5- Worst | Up to 24 months after CRT | 
| MD Anderson Symptom Inventory-Lung Cancer: Patient Report outcomes | Score Range 0-10 (0) No symptom and (10) worst symptoms | Up to 24 months after CRT | 
| Overall survival |  | Up to 10 years |