Characterizing Chemo-Radiotherapy Treatment-Related Cardiac Changes

Study Overview
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Brief Summary
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This trial studies cardiac changes after radiation or chemo-radiation for the treatment of lung or esophageal cancer that has not spread to other places in the body (non-metastatic) or has not come back (non-recurrent). Continuous cardiac monitoring with an implanted device may help to identify cardiac changes that would remain unnoticed, and facilitate the treatment of these early cardiac changes as part of standard care.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the 12-month cardiac event rate after radiation or chemo-radiation for the treatment of lung or esophageal cancer. EXPLORATORY OBJECTIVES: I. Define the spectrum of cardiac toxicity among chemoradiotherapy (CRT) patients at highest risk of cardiac toxicity. II. Establish the timeline of cardiac toxicity development and identify early predictive findings of permanent damage. III. Characterize the areas of the heart at highest risk for persistent cardiac damage. IV. Identify a dose response threshold for radiotherapy (RT) damage in different areas of the heart. V. Improve survival by alerting the cardiology team of the need for life-saving standard of care interventions. VI. Describe medical interventions employed for the cardiac events identified in the study. OUTLINE: Patients receive cardiac monitor implants then undergo standard of care RT or CRT at the discretion of the treating physician. Patients also undergo blood sample collection at baseline, 4 weeks, 3, 9, and 12 months. After completion of study treatment, patients are followed up at 4 weeks, 3, 9 and 12 months post RT.

Official Title
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Characterizing Chemo-Radiotherapy Treatment-Related Cardiac Changes

Conditions
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Stage IA1 Lung Cancer AJCC v8, Clinical Stage 0 Esophageal Adenocarcinoma AJCC v8, Clinical Stage 0 Esophageal Squamous Cell Carcinoma AJCC v8, Clinical Stage I Esophageal Adenocarcinoma AJCC v8, Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8, Clinical Stage II Esophageal Adenocarcinoma AJCC v8, Clinical Stage II Esophageal Squamous Cell Carcinoma AJCC v8, Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8, Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8, Localized Esophageal Carcinoma, Localized Lung Carcinoma, Pathologic Stage 0 Esophageal Adenocarcinoma AJCC v8, Pathologic Stage 0 Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage I Esophageal Adenocarcinoma AJCC v8, Pathologic Stage I Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage IA Esophageal Adenocarcinoma AJCC v8, Pathologic Stage IA Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage IB Esophageal Adenocarcinoma AJCC v8, Pathologic Stage IB Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage IC Esophageal Adenocarcinoma AJCC v8, Pathologic Stage II Esophageal Adenocarcinoma AJCC v8, Pathologic Stage II Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage IIA Esophageal Adenocarcinoma AJCC v8, Pathologic Stage IIA Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8, Pathologic Stage IIB Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage III Esophageal Adenocarcinoma AJCC v8, Pathologic Stage III Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8, Pathologic Stage IIIA Esophageal Squamous Cell Carcinoma AJCC v8, Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8, Pathologic Stage IIIB Esophageal Squamous Cell Carcinoma AJCC v8, Postneoadjuvant Therapy Stage I Esophageal Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage I Esophageal Squamous Cell Carcinoma AJCC v8, Postneoadjuvant Therapy Stage II Esophageal Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage II Esophageal Squamous Cell Carcinoma AJCC v8, Postneoadjuvant Therapy Stage III Esophageal Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage III Esophageal Squamous Cell Carcinoma AJCC v8, Postneoadjuvant Therapy Stage IIIA Esophageal Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IIIA Esophageal Squamous Cell Carcinoma AJCC v8, Postneoadjuvant Therapy Stage IIIB Esophageal Adenocarcinoma AJCC v8, Postneoadjuvant Therapy Stage IIIB Esophageal Squamous Cell Carcinoma AJCC v8, Stage 0 Lung Cancer AJCC v8, Stage I Lung Cancer AJCC v8, Stage IA2 Lung Cancer AJCC v8, Stage IA3 Lung Cancer AJCC v8, Stage IB Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, Stage IIA Lung Cancer AJCC v8, Stage IIB Lung Cancer AJCC v8, 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: Biospecimen Collection
* Device: Cardiac Event Monitor
* Other: Chemoradiotherapy
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years Planned standard of care curative thoracic RT or CRT with anticipated heart V40 > 20 cc (At least 20 cc of the heart should receive a dose of 40 gray [Gy] or higher) Able to follow-up at all specified standard of care time-points Patients can receive treatment as part of the standard of care or in a different study Receiving radiation treatment to an area close to the heart, for example gastroesophageal junction cancer, hilar lung cancer, or mainstem bronchus lung cancer Any type of systemic therapy or surgery before during or after radiation is acceptable Prior radiation to other areas is acceptable Planned radiation doses equal or higher than 40 Gy Exclusion Criteria: Metastatic disease Recurrent disease Patient receiving radiation prescription doses lower than 40 Gy No prior radiation that included any part of the heart is acceptable No thoracic re-irradiation

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (cardiac monitoring)<br>Patients receive cardiac monitor implants then undergo standard of care RT or CRT at the discretion of the treating physician. Patients also undergo blood sample collection at baseline, 4 weeks, 3, 9, and 12 months. | Procedure: Biospecimen Collection<br>* Undergo biospecimen collection<br>* Other names: Specimen Collection;Device: Cardiac Event Monitor<br>* Receive cardiac monitor<br>Other: Chemoradiotherapy<br>* Undergo CRT<br>* Other names: RT-CT;Radiation: Radiation Therapy<br>* Undergo RT<br>* Other names: Therapy, Radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac event rate at 12 months | The proportion of failures (cardiac event) will be estimated by the number of cardiac events divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner (1987). | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute adverse events (AE) | Descriptive statistics of frequency (percentage) will be used to summarize AE incidence and severity as measured by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0. 95% confidence intervals will be constructed around point estimates. | Within the first 6 months from the date of enrollment | 
| Incidence of late adverse events | Descriptive statistics of frequency (percentage) will be used to summarize AE incidence and severity as measured by the CTCAE 5.0. 95% confidence intervals will be constructed around point estimates. | After the first 6 months from the date of enrollment | 
| Loco-regional recurrence | Analyses will be descriptive in nature. Statistical tests on endpoints (t-test for continuous data; Wilcoxon rank-sum test, Fisher's exact test, or Chi-square test for ordinal data) will be utilized to determine differences at any particular time point. Graphical displays will be produced, such as mean profile plots or bar charts. | Up to 12 months | 
| Distant recurrence | Analyses will be descriptive in nature. Statistical tests on endpoints (t-test for continuous data; Wilcoxon rank-sum test, Fisher's exact test, or Chi-square test for ordinal data) will be utilized to determine differences at any particular time point. Graphical displays will be produced, such as mean profile plots or bar charts. | Up to 12 months | 
| Disease-free survival | Analyses will be descriptive in nature. Statistical tests on endpoints (t-test for continuous data; Wilcoxon rank-sum test, Fisher's exact test, or Chi-square test for ordinal data) will be utilized to determine differences at any particular time point. Graphical displays will be produced, such as mean profile plots or bar charts. | From study registration any local, regional, distant failure, or death, assessed up to 12 months | 
| Cause specific survival | Analyses will be descriptive in nature. Statistical tests on endpoints (t-test for continuous data; Wilcoxon rank-sum test, Fisher's exact test, or Chi-square test for ordinal data) will be utilized to determine differences at any particular time point. Graphical displays will be produced, such as mean profile plots or bar charts. | From registration to death due to cancer, assessed up to 12 months | 
| Cardiac event free survival | Analyses will be descriptive in nature. Statistical tests on endpoints (t-test for continuous data; Wilcoxon rank-sum test, Fisher's exact test, or Chi-square test for ordinal data) will be utilized to determine differences at any particular time point. Graphical displays will be produced, such as mean profile plots or bar charts. | From registration to cardiac event or death, assessed up to 12 months | 
| Cardiac death | Cardiac death would include documented congestive heart failure, myocardial infarction, arrhythmia, heart block, or any other cardiac cause documented in the medical records, death certificate, or autopsy as one of the major contributing causes of death. Analyses will be descriptive in nature. Statistical tests on endpoints (t-test for continuous data; Wilcoxon rank-sum test, Fisher's exact test, or Chi-square test for ordinal data) will be utilized to determine differences at any particular time point. Graphical displays will be produced, such as mean profile plots or bar charts. | From registration to death due to cardiac reasons, assessed up to 12 months | 
| Overall survival | Analyses will be descriptive in nature. Statistical tests on endpoints (t-test for continuous data; Wilcoxon rank-sum test, Fisher's exact test, or Chi-square test for ordinal data) will be utilized to determine differences at any particular time point. Graphical displays will be produced, such as mean profile plots or bar charts. | From registration to death due to any cause, assessed up to 12 months |