Cardiotoxicity in Breast Cancer Patients Treated With Proton or Photon Radiotherapy: A RadComp Companion Study

Study Overview
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Brief Summary
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This is a companion study to the Pragmatic Randomized Trial of Proton vs Photon Therapy for Patients with non-Metastatic Breast Cancer Receiving Comprehensive Nodal Radiation: A Radiotherapy Comparative Effectiveness (RadComp) Consortium Trial (NCT02603341). The investigators will collect cardiovascular (CV) biomarkers and echocardiograms prior to, during, and for up to 1 year following radiation for a subset of patients enrolled on RadComp and to evaluate the impact of proton vs photon radiation therapy (RT) on CV function and structure.

Detailed Description
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The study population of the companion study will consist of newly enrolled RadComp trial participants. Patients on this ancillary will be consented prior to RadComp randomization to decrease the bias secondary to RT type and enhance internal validity. The study will define the early changes in biomarkers, imaging measures, and RT dose volume metrics and long-term (5-10 year) CV clinical outcomes using the RadComp parent study's infrastructure for clinical data collection and long-term follow-up. Blood samples, echocardiograms, and questionnaires are obtained at baseline (between end of chemotherapy and start of RT), immediately after the end of RT, and at 6 months and 12 months after the end of RT. An additional blood sample will be collected at 4 weeks after the start of RT. Clinical, demographic, and patient reported outcomes data are collected as part of the RadComp parent study. In addition to data collected by RadComp, we will collect a limited set of clinical data and two additional quality of life instruments for the companion study.

Official Title
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Cardiotoxicity in Breast Cancer Patients Treated With Proton or Photon Radiotherapy: A RadComp Companion Study

Conditions
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Breast Cancer, Cardiotoxicity

Intervention / Treatment
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* Radiation: Proton vs Photon Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consented to RadComp Willing and able to provide written consent Exclusion Criteria: Knowledge of randomization on RadComp prior to enrollment on companion study Non-diagnostic echocardiography windows as assessed on local read.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ancillary Cohort<br>No Intervention: Subjects will be followed before, during and for up to 1 year after radiation with echocardiogram, blood draw, and symptoms and activity survey. | Radiation: Proton vs Photon Radiation<br>* Assignment to proton vs photon by randomization on RadComp parent study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular ejection fraction (LVEF) | Change in echocardiography derived LVEF from baseline | 14 months | 
| Right Ventricular (RV) Fractional Area Change (FAC) | Change in echocardiography derived RV FAC from baseline | 14 months | 
| Circulating N-terminal pro B-type natriuretic peptide (NTproBNP) | Change in NTproBNP levels from baseline | 14 months | 
| Circulating Placental Growth Factor (PIGF) | Change in PIGF levels from baseline | 14 months | 
| Circulating Growth Differentiation Factor-15 (GDF-15) | Change in GDF-15 levels from baseline | 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LV systolic strain | Change in 2D echocardiography derived LV global longitudinal strain and circumferential strain from baseline | 14 months | 
| Echocardiography derived Ventricular Arterial Coupling Measurement | Change from baseline in ventricular arterial coupling as defined by end systolic elastance divided by effective arterial elastance | 14 months | 
| Diastolic function (E/e') | Change in E/e' from baseline as measured by echocardiogram | 14 months | 
| Circulating Troponin T(TnT) | Change in high-sensitivity TnT levels from baseline | 14 months | 
| Circulating high-sensitivity C-Reactive Protein (hsCRP) | Change in hsCRP levels from baseline | 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardio-Oncology, Radiation Therapy Cardiotoxicity