Multicenter Randomized Pivotal Stage Clinical Investigation Assessing the Communication of an Individualized AI-based Risk Prediction of Arm Lymphedema to Breast Cancer Patients With an Indication for Regional Lymph Node Irradiation and Their Physician as Part of Treatment Shared-decision
Trial ID: NCT07187726
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: NA
Start date: 2025-10-07
Completion date: 2029-01-31
Sponsor: UNICANCER
Conditions: Unilateral Breast Neoplasms
Interventions: XAINET AI tool
Locations: Centre Marie Curie; Centre Pierre Curie; Clinique Tivoli Ducos; ROC 37; CHI Créteil; Centre Georges François Leclerc; Centre Guillaume Le Conquérant; Centre Antoine Lacassagne; Institut Godinot; ICO Nantes Saint Herblain; Institut de Cancérologie Strasbourg Europe; Gustave Roussy
Countries: France; France; France; France; France; France; France; France; France; France; France; France
Enrollment: 724
Age range: 18 Years - None
Sex: FEMALE

Summary:
Radiotherapy after breast cancer surgery can lead to side effects like arm lymphedema (arm swelling). Lymphedema can cause long-term discomfort and affect quality of life.

The goal of this clinical investigation is to determine whether using an artificial intelligence (AI) tool to predict the risk of developing arm lymphedema after breast cancer radiotherapy can help patients and physicians make better treatment decisions.

This AI tool has been developed to determine each patient's personalized risk of developing lymphedema. The risk is shown using a web app that explains the factors involved and offers suggestions like using a compression sleeve to reduce the risk.

Women (≥18 years) with breast cancer (cT1-4, cN0-N3, M0) requiring regional lymph node irradiation post-mastectomy or breast-conserving surgery are eligible, regardless of hormone receptor status, tumor grade, or HER2 status.

Patients will be randomly divided into two groups:

* Experimental group: Patients and physicians will see the AI-predicted risk and use it to guide treatment choices.
* Control group: The risk is not shown.

The radiotherapy treatment will be exactly the same as the treatment that you would have received if you had not taken part in this clinical investigation. The only intervention will be whether or not the risk you are informed of the risk of developing lymphedema.

All patients will be followed for two years to monitor:

* How risk communication influences radiotherapy treatment choices
* The occurrence of side effects
* The predictive performance of the AI tool
* Patients' quality of life
* Compliance with compression sleeve use
* Loco-regional recurrence-free survival, distant disease-free survival, and overall survival

Eligibility criteria:
Inclusion Criteria:

1. Patient must have signed a written informed consent form prior to inclusion visit and to any study specific procedures
2. Women ≥ 18 years
3. Patients with unilateral invasive breast cancer, cT1-4, cN0-N3, M0 who had undergone radical surgery defined as mastectomy or breast conservation surgery with negative margins +/- (neo)-adjuvant systemic treatment. The patient can be included no matter the status of estrogen and progesterone receptors, malignancy grade, and HER2 status
4. Axillary lymph node staging (by axillary dissection or sentinel lymph node biopsy and/or marked lymph node biopsy \[Marking Axillary lymph nodes with Radioactive Iodine seeds (MARI) procedure/ (Targeted Axillary Dissection (TAD) procedure\] in case of neo-adjuvant systemic treatment) defining the indication for regional nodal irradiation to levels I+/- II+/- III+/- IV+/- interpectoral nodes (Rotter) +/- the IMC(Internal Mammary Chain)
5. ECOG performance status 0-2
6. Patient must be randomized within the recommended time period from last surgery or the last series of chemotherapy whichever comes last as per national or institutional guidelines in order not to delay radiotherapy treatment start
7. Women of childbearing potential must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of radiotherapy
8. Patient is willing and able to comply with the protocol for the duration of the clinical investigation including undergoing treatment and scheduled visits, and examinations including follow-up
9. Patient affiliated to or a beneficiary of the local social security system, health service or other local regulatory requirements

Exclusion Criteria:

1. Previous breast cancer or Ductal Carcinoma in Situ (DCIS) of the ipsilateral breast
2. Bilateral breast cancer
3. Patient with previous non-breast malignancy, with the exception of cancer in complete remission for over 5 years and low risk of recurrence. Patients with the following diseases can be accepted despite less than 5 years disease free interval: carcinoma in situ of the cervix, melanoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin
4. Patient who has an indication for boost to one or more regional nodes
5. Previous radiation therapy to the chest region
6. Patients having arm swelling requiring arm sleeve prescription at baseline
7. Any condition that prevents the patient from wearing a compression sleeve for 8h/day from the first day of radiation therapy until 3 months after the initiation of adjuvant radiotherapy
8. Pregnant or breastfeeding women
9. Patient already included in another therapeutic study involving radiotherapy dose/regimen/technique and/or arm lymphedema risk
10. Person deprived of their liberty or under protective custody or guardianship
11. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Outcomes:
Arm lymphedema