Axillary Reverse Mapping in Preventing Lymphedema in Patients With Breast Cancer Undergoing Axillary Lymph Node Dissection

Study Overview
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Brief Summary
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This phase III trial studies how well axillary reverse mapping works in preventing lymphedema in patients with breast cancer undergoing axillary lymph node dissection. Axillary reverse mapping may help to preserve the lymph node drainage system around the breast so as to prevent lymphedema after surgery.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the occurrence of post-surgery lymphedema by conical geometric measures in clinical T1-3, N0-3, M0 breast cancer patients undergoing axillary surgery and randomized to Group 1 (no axillary reverse mapping [ARM]) versus Group II (ARM). SECONDARY OBJECTIVES: I. To compare between the study groups the lymphedema symptom intensity and distress as measured by the Lymphedema Symptom Intensity and Distress Survey-Arm (LSIDS-A). II. To evaluate the technical success of performance of ARM procedure: Identification of ARM lymphatics, and the ability to spare or reapproximate ARM lymphatics. III. To compare the rate of regional recurrence between patients randomized to receive ARM versus no ARM. EXPLORATORY OBJECTIVES: I. To assess the occurrence of lymphedema as a function of radiotherapy use and targets. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive isosulfan blue subcutaneously (SC) and undergo axillary lymph node dissection (ALND). GROUP II: Patients undergo ARM. Patients then receive isosulfan blue and undergo ALND as in Group I. After completion of study, patients are followed up for 3 years.

Official Title
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ARM: Axillary Reverse Mapping - A Prospective Trial to Study Rates of Lymphedema and Regional Recurrence After Sentinel Lymph Node Biopsy and Sentinel Lymph Node Biopsy Followed by Axillary Lymph Node Dissection With and Without Axillary Reverse Mapping

Conditions
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Breast Cancer Stage I, Breast Cancer Stage II, Breast Cancer Stage III

Intervention / Treatment
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* Drug: Isosulfan Blue
* Procedure: Axillary Lymph Node Dissection
* Procedure: Mapping
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documentation of Disease: cT1-3 patients undergoing axillary surgery who additionally meet one of the following conditions: Clinically node negative patients undergoing mastectomy and sentinel lymph node biopsy (SLNB) with possible axillary lymph node dissection (ALND) if SLNB is positive. If ALND is performed during a separate operation, ARM procedure must be repeated. Clinically node negative is defined by i) negative clinical exam and/or ii) negative axillary US and/or iii) negative needle biopsy of sonographically suspicious axillary nodes as applicable to each case. Clinically node positive patients as determined by needle biopsy and planned for ALND regardless of type of breast surgery. Patients will be staged according to the TNM staging system. Prior Treatment: No prior axillary surgery except needle biopsy or concurrent SLNB. o Prior neoadjuvant chemotherapy is allowed but must be completed at least 2 weeks before registration. No prior history of ipsilateral breast cancer (invasive or ductal breast carcinoma in situ [DCIS]). Lobular breast carcinoma in situ (LCIS) and benign disease are allowed. (May have neoadjuvant chemotherapy which must be completed 2 weeks before registration). No bilateral invasive breast cancer. No matted nodes. No history of lymphedema of either arm. No known allergies blue dyes, including make-up containing blue dye. In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English. Female : Men are excluded from this study because the number of men with breast cancer is insufficient to provide a statistical basis for assessment of effects in this subpopulation of people with breast cancer. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. Creatinine: =< 1.5 x upper limit of normal (ULN).

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group I (ALND)<br>Patients receive isosulfan blue SC and undergo ALND. | Drug: Isosulfan Blue<br>* Given SC<br>Procedure: Axillary Lymph Node Dissection<br>* Undergo ALND<br>* Other names: axillary dissection;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Group II (ARM, ALND)<br>Patients undergo ARM. Patients then receive isosulfan blue and undergo ALND as in Group I. | Drug: Isosulfan Blue<br>* Given SC<br>Procedure: Axillary Lymph Node Dissection<br>* Undergo ALND<br>* Other names: axillary dissection;Procedure: Mapping<br>* Undergo ARM<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of upper extremity (UE) lymphedema | Will be assessed by the Lymphedema Symptom Intensity and Distress Survey-Arm (LSIDS-A). The LSIDS-A questionnaire contains two different scales for intensity and distress measured from 1 (slight) to 5 (severe). The LSIDS-A questionnaire scores for swelling in the arm, decreased physical activity, pain in the arm, and loss of confidence in one's body will be evaluated for the change of baseline to 36 months using a two-sample, two-sided t-test. | Up to 36 months post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in health-related quality of life: LSIDS-A questionnaire scores | Will be assessed by the Lymphedema Symptom Intensity and Distress Survey-Arm (LSIDS-A). The LSIDS-A questionnaire scores at each time point, as well as the change from baseline will be compared between groups by a two-sample, two-sided t-test. If there is evidence of non-normality (via Shapiro-Wilk testing), will use a non-parametric procedure such as Wilcoxon rank sum test. Further analysis will include linear mixed model using data from all time points to compare the LSIDS-A questionnaire scores between the two treatment groups over time adjusting for other baseline characteristics. Will evaluate the pattern of missing data. If the drop-out rate is higher than expected, methods proposed by Hogan and Laird will be used to assess whether the presence of drop-outs affects inferences obtained from the repeated measures analyses. Appropriate methods will be used to address missingness. | Baseline to 36 months | 
| Incidence of regional recurrence | The technical success will be summarized using a binomial point estimate and 95% confidence interval (CI) and will be compared using a two-sample test of proportions. | Up to 3 years | 
| Technical success of performance of axillary reverse mapping (ARM) procedure (defined as identification of ARM lymphatics, and the ability to spare or reapproximate ARM lymphatics) | The cumulative incidence of regional recurrence will be summarized using the cumulative incidence function treating death without regional recurrence as the competing risk. Similar analysis methods described for the primary endpoint will be used to compare the cumulative incidence of regional recurrence between group I and II. | Up to 3 years |