The Differential Impact of Proton Beam Irradiation Versus Conventional Radiation on Organs-at-risk in Stage II-III Breast Cancer Patients

Study Overview
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Brief Summary
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The objective of the study is to serve as a correlative study for patients enrolled on the RadCOMP trial (NCT02603341), a randomized phase III study of stage II and III breast cancer patients treated with either conventional photon radiation or proton beam radiation

Official Title
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The Differential Impact of Proton Beam Irradiation Versus Conventional Radiation on Organs-at-risk in Stage II-III Breast Cancer Patients

Conditions
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Breast Cancer Stage II, Breast Cancer Stage III

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for and scheduled to receive radiation therapy on Radiation Therapy Oncology Group (RTOG) Trial 3510 (Pragmatic Phase III 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) Ability to understand and the willingness to sign a study-specific written informed consent document Exclusion Criteria: There are no exclusion criteria.

Ages Eligible for Study
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Minimum Age: 21 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 |
| --- | --- |
| Photon Therapy<br>The patients being treated on the Radiotherapy Comparative Effectiveness (RADCOMP) Consortium Trial (NCT02603341) at Massachusetts General Hospital that were randomized to receive photon therapy. | |
| Proton Therapy<br>The patients being treated on the Radiotherapy Comparative Effectiveness (RADCOMP) Consortium Trial (NCT02603341) at Massachusetts General Hospital that were randomized to receive proton therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Global Longitudinal Strain (GLS) | Comparison of the change in GLS between conventional radiation and proton beam radiation groups. Participants who decrease their GLS by at least 2% 6-8 months following radiation therapy will be considered to demonstrate a significant decrement in GLS. | Baseline, 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular Ejection Fraction (LVEF) Using Echocardiography | Comparison of the change in LVEF between conventional radiation and proton beam radiation groups. Reduced cardiac function is defined as an ejection fraction <50%. | Baseline, end of treatment (approximately 10 weeks), then 6, 12, 24, 36, and 60 months post treatment | 
| Radiation-induced Lung Parenchymal Changes Using CT Imaging | Radiation-induced lung parenchymal changes will be assess with non-contrast enhanced computerized tomography (CT) scans and incidence will be estimated in each radiation group by the cumulative incidence function and compared using Gray's test. Among patients who do not have any changes detected, death and disease progression will be considered as competing risks. | Baseline, 3,6,12, months post treatment | 
| Incidence of Thyroid Dysfunction | Incidence of thyroid insufficiency will be estimated in each radiation group by the cumulative incidence function and compared using Gray's test. In the absence of thyroid dysfunction, death and disease progression will be considered as competing risks. | Baseline, end of treatment (approximately 10 weeks), then 12, 24, 36, and 60 months post treatment | 
| Incidence of Ipsilateral Arm Lymphedema | Incidence of ipsilateral arm lymphedema will be estimated in each radiation group by the cumulative incidence function and compared using Gray's test. | Baseline, end of treatment (approximately 10 weeks), then 6, 12, 24, 36, and 60 months post treatment | 
| Severity of Ipsilateral Arm Lymphedema | Serial arm measurements may be analyzed using mixed effects model to compare the severity of ipsilateral arm lymphedema over time between the radiation groups. | Baseline, end of treatment (approximately 10 weeks), then 6, 12, 24, 36, and 60 months post treatment | 
| Ipsilateral Breast/Chest Wall Cosmesis | Breast cosmesis will be assessed with characteristics graded on a four-point scale. Assessments will be performed by a trained nurse/nurse practitioner using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System for Breast Cancer. Incidence of adverse cosmesis (2=fair or 3=poor score) will be estimated in each radiation group by the cumulative incidence function and compared using Gray's test. Among patients without adverse breast cosmesis, death and disease progression will be considered as competing risks. | Baseline, end of treatment (approximately 10 weeks), then 6, 12, 24, 36, and 60 months post treatment |