A Randomized Comparison of Radiation Therapy Techniques in the Management of Node Positive Breast Cancer

Phase 1

Completed

Conditions: Breast Cancer

Interventions: Radiation: 3D
Radiation: IMRT

Registration Number: NCT00581256

Lead Sponsor: University of Michigan Rogel Cancer Center

Brief Summary: Radiotherapy has been shown to reduce breast-cancer specific mortality in patients at high risk for distant dissemination. It has also been shown to increase rates of non-breast cancer deaths and morbidity due to cardiovascular and pulmonary toxicity. Although treatment planning has improved significantly through the years, recent reports still demonstrate treatment-related morbidity even with 3-dimensional planned techniques. Thus, while 3D planning represents the state of the art treatment for loco-regional radiotherapy for breast cancer, further improvement is needed to continue to decrease heart and lung exposure. The ultimate goal of the proposed research is to determine whether treatment planning using intensity-modulated radiotherapy (IMRT), the "next generation" of radiation treatment delivery systems, results in less radiation exposure to the heart and lungs than the best current RT technique in women with node positive breast cancer. This proposal will test the potential clinical value of IMRT compared to the best standard 3D plan (partially wide tangent fields, PWTF) in the treatment of breast cancer. These two treatment techniques will be studied in a Phase II randomized trial using quantitative indicators of potential cardiac and lung toxicity. The preliminary data generated from this trial will be used to ultimately justify a multi-institutional comparison of the two treatment techniques with long-term clinical cardiac and pulmonary toxicity as endpoints.

Detailed Description: 1. Primary Objective 1.1 To compare the extent of new myocardial perfusion defects following breast cancer radiotherapy using the best standard 3-D radiotherapy technique, partially wide tangent fields, versus the best optimized technique.

2. Secondary Objectives 2.1 To compare changes in ejection fraction and alterations in cardiac wall motion with treatment by technique 2.2 To compare changes in lung perfusion defects and pulmonary function tests (DLCO, FEV1, and FVC) by technique 2.3 To compare rates of pericarditis and pneumonitis by technique

Cardiac Endpoints: Myocardial SPECT-CT perfusion defects, ejection fraction, alterations in cardiac wall motion, per SPECT-CT (adenosine stress and rest (if necessary)) scan.

Pulmonary Endpoints: Lung SPECT-CT perfusion defects per SPECT-CT scan, and changes in pulmonary function tests: DLCO, FEV1, FVC Clinical Endpoints: pericarditis and pneumonitis.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

Inclusion Criteria

Eligibility Criteria

Breast cancer diagnosis: Patients must have histologically confirmed adenocarcinoma of the breast requiring comprehensive loco-regional irradiation that includes treatment to the intact breast/chest wall, supraclavicular (SCV), infraclavicular nodes (ICV), and internal mammary nodes (IMN).
Patients must have pathologic T 1, 2, 3 or 4, N 1, 2, or 3 Stage II or III disease as defined by the AJCC Staging System, 6th edition. Patients who do not undergo axillary staging but are at risk for nodal involvement may also be treated.
All patients must have left-sided breast cancer.
Both men and women are eligible.
Patients must be adults (18 years of age or older)
For women of child-bearing age, effective contraception must be used. A written statement must be obtained that the patient is not pregnant. If there is any question of pregnancy at time of therapeutic RT or at time of each SPECT-CT scan, a pregnancy test will be done to confirm the patient is not pregnant.
Performance status should be 0-2 by ECOG criteria.
Patients that have received prior RT may be enrolled on the present study if the new breast lesion can be treated with no overlap of RT fields.
Patients must be aware of the neoplastic nature of her/his disease.
Patients must be informed of the investigational nature of this study and must sign an informed consent in accordance with the Institutional Review Board (IRB) of the University of Michigan and federal guidelines.
Patients' blood tests should indicate they are able to tolerate radiotherapy. Tests must be done within 28 days of registration:

CBC with differential and platelet count (Hemoglobin > 8.0 g/dl; wbc > 2000/mm3; absolute neutrophil count > 1000/mm3; platelet count > 75,000/mm3.

Exclusion Criteria

Patients who are pregnant or are nursing are excluded.
Pathologically node negative breast cancer unless treated with neo-adjuvant chemotherapy.
Performance status > 2 by ECOG criteria
Patients who are unable to lie on their back and raise their arm above their head in the treatment planning position for radiotherapy
Patients with a clinically unstable medical condition
Patients with a life-threatening disease state
History or suspicion of serious life-threatening allergic reaction to Tc-99m imaging agents.
Patients that have had breast-conservation surgery with positive margins or any patient with negative margins with a tumor positive for an extensive intraductal component.
Patients that are not able to use the ABC device.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	3D	Best 3-dimensional standard PWTF technique
1	IMRT	Best Delivery-optimized radiotherapy technique (IMRT)

Primary Outcome Measures

Name	Time	Method
The Number of Participants With a Significant Increase in Perfusion Defects (PD)	1 Year	To compare the extent of new myocardial perfusion defects following breast cancer radiotherapy using the best standard 3-D radiotherapy technique, partially wide tangent fields, versus the best optimized technique. Perfusion defects (PD) were assessed by comparing normalized perfusion distributions against our institution's normal polar map databases for the left anterior descending artery (LAD) using thresholds of 2.5-SD (standard deviation) and 1.5-SD below the normal mean. On the basis of interest variability, a PD increase greater than 5% or 10% was considered significant for 2.5- and 1.5-SD thresholds, respectively.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With New Lung Perfusion Defects	baseline to approx 1 year	To compare changes in lung perfusion defects by treatment arm. Perfusion defects (PD) were assessed by comparing normalized perfusion distributions against our institution's normal polar map databases for the left anterior descending artery (LAD).
Mean Percent Change in Ejection Fraction (LVEF)	baseline to approx 1 year	To compare change in ejection fraction between treatment arms.
The Number of Participants That Experience Pericarditis and Pneumonitis	approx 1 year	To compare rates of pericarditis and pneumonitis by treatment arm. Pericarditis (inflammation of the pericardium): Grade1: Asymptomatic, ECG or physical exam; changes consistent with pericarditis Grade 2: Symptomatic pericarditis Grade 3: Pericarditis with physiologic consequences Grade 4: Life-threatening Pneumonitis (inflammation of the walls of the alveoli in the lungs) Grade 1: Asymptomatic, radiographic findings only Grade 2: Symptomatic, not interfering with ADL (activities of daily living) Grade 3: Symptomatic, interfering with ADL Grade 4: Life-threatening