ALND vs ART in Positive Sentinel Node After Neoadjuvant Therapy in Breast Cancer

Study Overview
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Brief Summary
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In the case of primary surgery, in patients with sentinel node involvement, it has already been shown that omitting axillary lymph node dissection (ALND), often combining axillary radiotherapy (RT), does not worsen the prognosis and does significantly reduce the appearance of lymphedema. However, patients who have received neoadjuvant systemic treatment cannot benefit from this option, even though in the majority of those who have responded well to treatment, a residual disease in the armpit is low, but there are no studies yet published that supports the possibility of not performing lymphadenectomy. The primary endpoint is to evaluate wether axillary radiotherapy (ART) presents a lower risk of lymphedema with respect to lymphadenectomy (ALND) in patients with breast cancer who, after neoadjuvant systemic treatment (NST), present the sentinel node affected. Likewise, we will evaluate recurrences and overall survival in both groups. Finally, we will analyze the quality of life of these patients.

Detailed Description
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A prospective, randomized, open-label, parallel-assigned, multicenter study. The estimated sample size is 1660 patients, over 5 years. Patients will be stratified and analyzed independently according to the neoadjuvant treatment regimen, whether chemotherapy (CT) +/- hormonal therapy (HT). A pilot phase of the study was carried out with the first 200 patients. An interim analysis will also be performed with the first 820 patients recruited.

Official Title
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Axillary Lymph Node Dissection Versus Axillary Radiotherapy in Breast Cancer Patients With Positive Sentinel Node After Neoadjuvant Therapy: A Multicenter Randomized Study

Conditions
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Chemotherapy, Breast Cancer, Sentinel Lymph Node, Axillary Lymph Nodes Dissection, Radiotherapy Side Effect

Intervention / Treatment
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* Radiation: Axillary Radiotherapy
* Procedure: Lymphadenectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T1-T4 N0/ T0-T4 N1 at diagnosis and subsidiary of neoadjuvant treatment Post-CT SLN with ≤2 macrometastasis/micrometastasis or ITCs Post-CT axillary response by ultrasound or MRI Complete at least 3 months of neoadjuvant chemotherapy and 6 months of endocrine treatment. Exclusion Criteria: cN2 ypN0 History of breast surgery for ipsilateral cancer in the last 10 years History of other cancer in the last 5 years, except squamous carcinoma of the skin.

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective, randomized, multicenter study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axillary radiotherapy without lymphadenectomy<br>Axillary radiotherapy (level I and II) + level III and supraclavicular +/- internal mammary chain without lymphadenectomy | Radiation: Axillary Radiotherapy<br>* Axillary radiotherapy without lymphadenectomy (level I and II) + level III and supraclavicular +/- internal mammary chain<br>|
| Active Comparator: Axillary lymph node dissection<br>Axillary lymph node dissection + radiotherapy level III and supraclavicular +/- internal mammary chain | Procedure: Lymphadenectomy<br>* Axillary Lymph node dissection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | To assess whether the irradiation of the axilla concerning axillary lymph node dissection is not inferior in disease-free survival, in patients with positive sentinel lymph node (SN) after neoadjuvant systemic treatment. | From date of diagnosis until the date of first documented recurrence or death, wichever came first,assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | To assess whether the irradiation of the axilla concerning axillary lymph node dissection is not inferior in overall survival, in patients with positive sentinel lymph node (SN) after neoadjuvant systemic treatment. | From date of diagnosis until the date of death from any cause, assessed up to 5 years | 
| Lymphedema Incidence | Volume difference between both arms (cm^3) above 10% | From date of surgery until the date of first lynphedema apparition, assessed up to 3 years |