Intensity Modulated Radiation Therapy or 3-Dimensional Conformal Radiation Therapy in Treating Patients With Lymph-Node Positive Breast Cancer

Study Overview
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Brief Summary
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This phase II trial studies the shoulder morbidity in patients with lymph-node positive breast cancer receiving intensity modulated radiation therapy or 3-dimensional conformal radiation therapy. Intensity modulated radiation therapy may cause less shoulder/arm morbidity in patients with lymph-node positive breast cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if intensity modulated radiation therapy (IMRT) reduces average 1-year patient-reported shoulder/arm morbidity in women receiving regional nodal irradiation (RNI) for lymph-node positive breast cancer as compared to historical data. SECONDARY OBJECTIVES: I. To measure patient-reported shoulder/arm morbidity in women receiving RNI with 3-dimensional conformal radiation therapy (3DCRT) for lymph-node positive breast cancer. II. To measure change in shoulder range of motion in women receiving RNI. III. To measures rates of ipsilateral upper extremity lymphedema in women receiving RNI. IV. To explore the dose volume parameters to the shoulder/neck/trunk musculature associated with worsening patient-reported shoulder/arm morbidity. V. To assess disease outcomes in patients treated with IMRT. VI. To measure long-term patient-reported shoulder/arm morbidity in women receiving RNI with IMRT or 3DCRT. OUTLINE: Patients are assigned to 1 of 2 arms. ARM A: Patients undergo IMRT over 5 weeks. ARM B: Patients undergo 3DCRT over 5 weeks. After completion study treatment, patients are followed up at 1, 6, and 12 months, and then annually for up to 5 years.

Official Title
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Prospective Evaluation of Shoulder Morbidity in Patients With Lymph-Node Positive Breast Cancer Receiving Regional Nodal Irradiation

Conditions
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Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Lymph Node Involvement, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8

Intervention / Treatment
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* Radiation: 3-Dimensional Conformal Radiation Therapy
* Radiation: Intensity-Modulated Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven diagnosis of breast cancer Patients that receive neoadjuvant systemic therapy (chemotherapy, anti-HER2 therapy, or endocrine therapy) are eligible History/physical examination within 60 days prior to study entry Patients who have undergone either a lumpectomy or mastectomy are eligible Patients that have undergone any type of breast reconstruction are eligible The interval between the date of last surgery or chemotherapy and registration must be =< 84 days Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of start of radiation therapy Women of childbearing potential must be non-pregnant and non-lactating and willing to use medically acceptable form of contraception during radiation therapy Patients must provide study specific informed consent prior to study entry Exclusion Criteria: Clinical or radiologic evidence of distant metastases Patients with known unresected disease in the axillary apex or supraclavicular fossa Prior invasive or in-situ carcinoma of the breast (prior lobular breast carcinoma in situ [LCIS] is eligible) Prior surgery to the ipsilateral shoulder for any condition Baseline impaired mobility of the ipsilateral shoulder from a condition not related to the breast cancer surgery as determined by the treating physician Non-epithelial breast malignancies such as sarcoma/lymphoma Prior radiotherapy to the breast or prior radiation to the region of the ipsilateral breast that would result in overlap of radiation fields Medical, psychiatric, or other conditions that would prevent the patient from receiving the protocol therapy or providing informed consent Pregnancy or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception Active systemic lupus, erythematosus, or any history of scleroderma, dermatomyositis with active rash

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (IMRT)<br>Patients undergo Intensity-Modulated Radiation Therapy over 5 weeks. | Radiation: Intensity-Modulated Radiation Therapy<br>* Undergo IMRT<br>* Other names: Intensity-Modulated Radiotherapy;|
| Experimental: Arm B (3DCRT)<br>Patients undergo 3-Dimensional Conformal Radiation Therapy over 5 weeks. | Radiation: 3-Dimensional Conformal Radiation Therapy<br>* Undergo 3DCRT<br>* Other names: Radiation Conformal Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shoulder/arm morbidity assessed by Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire in patients treated with intensity modulated radiation therapy (IMRT) | DASH questionnaire in patients treated with IMRT to assess shoulder/arm morbidity. Patients that have a DASH score of ≥15 at 1 year post-treatment will be considered as having persistent shoulder morbidity. The full scale range is 0-100. | At 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shoulder/arm morbidity assessed by DASH questionnaire in patients treated with 3-dimensional conformal radiation therapy (3DCRT) | DASH questionnaire in patients treated with 3DCRT to assess shoulder/arm morbidity. Patients that have a DASH score of ≥15 at 1 year post-treatment will be considered as having persistent shoulder morbidity. | At 1 year | 
| Changes in shoulder range of motion for flexion, abduction, internal and external rotation using a goniometer as defined by the American Academy of Orthopedic Surgeons | Using a goniometer as defined by the American Academy of Orthopedic Surgeons to measure changes in shoulder range of motion for flexion, abduction, internal and external rotation | At baseline, 1 month, 6 months and 12 months post-radiation | 
| Measure rates of upper extremity lymphedema using arm circumference with a tape measure | Measure rates of upper extremity lymphedema using arm circumference using a tape measure | At baseline, 1 month, 6 months and 12 months post-radiation | 
| Measure rates of upper extremity lymphedema using a perometer | Measure rates of upper extremity lymphedema using arm circumference using a perometer | At baseline, 1 month, 6 months and 12 months post-radiation | 
| Dosimetric parameters associated with worse arm/shoulder morbidity as measured by the DASH | Dosimetric parameters (the volume of shoulder receiving 5-50 Gy) associated with worse arm/shoulder morbidity as measured by the DASH | Up to 5 years | 
| Rates of loco-regional control in patients treated with IMRT | Rates of loco-regional control, distant metastases, and overall survival in patients treated with IMRT | At 5 years | 
| Distant metastases in patients treated with IMRT | The cumulative incidence of distant metastases at 5 years in patients treated with IMRT control, distant metastases | At 5 years | 
| Overall survival in patients treated with IMRT | Kaplan-Meier method will be used to estimate the 5-year overall survival in patients treated with IMRT | Up to 5 years | 
| Shoulder/arm morbidity using the DASH questionnaire in patients treated with IMRT | DASH questionnaire in patients treated with IMRT to assess shoulder/arm morbidity using full scale range 0-100 | Up to 5 years | 
| Shoulder/arm morbidity using the DASH questionnaire in patients treated with 3DCRT | DASH questionnaire in patients treated with 3DCRT to assess shoulder/arm morbidity | Up to 5 years |