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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer Stage II; Breast Cancer Stage III

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients enrolled at Massachusetts General Hospital on the 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).

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Photon Therapy; 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; 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?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Rachel Jimenez, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2017
• Primary Completion (Actual): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: August 31, 2017
• First Posted (Actual): September 1, 2017

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 17-031

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No