Precision Regional Node Irradiation for Sentinel Node-positive Breast Cancer

A Prospective Study of Individualized Regional Node Irradiation for Sentinel Node-positive Breast Cancer Without Axillary Dissection Based on Clinical and Genomic Risk Assessment

Axillary lymph node dissection has long been regarded as standard if treatment of the axilla is indicated for patients with a positive sentinel node. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. Since the publication of IBCSG23-01, ACOSOG Z0011 and AMAROS study, these studies indicated that there was no significant difference in recurrence and overall survival rates between the ALNB and SLNB+ALND followed by adjuvant radiotherapy. Therefore, an adaptation of the strategy to omit axillary lymph node dissection in patients with low-risk axillary involvement who are treated with curative surgery and systematic therapy. However, they also pose new challenges for adjuvant radiotherapy decisions. In the Z0011 study, patients were required to receive breast tangent field radiotherapy. In the AMAROS study, axillary radiotherapy included level I-III axillary lymph node drainage areas and the supraclavicular area, but the study results showed a local recurrence rate of only 1.19% at 5 years in the axillary radiotherapy group. Consequently, there is considerable controversy among clinical experts about whether a combined regional lymphatic drainage area radiotherapy strategy is necessary for low-burden sentinel lymph node metastasis breast cancer patients. In contrast, results from the EORTC-22922 and MA-20 studies, which included patients undergoing axillary lymph node dissection, showed that adjuvant radiotherapy to the entire lymphatic drainage area, including the internal mammary region, reduced the risk of disease-free survival and breast cancer-specific mortality. Therefore, the adjuvant radiotherapy strategy for early breast cancer patients with low-burden sentinel lymph node metastasis remains controversial, with a lack of high-level evidence to support it.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer Invasive
• Intervention / Treatment: Radiation: SLND(clinical low risk); Radiation: Sentinel Lymph Node Dissection(SLND) + axillary lymph node dissection(ALND); Radiation: SLND(clinical high risk, genomic low risk); Radiation: SLND alone ,clinical high risk and genomic high risk group

• Study Type: Interventional
• Enrollment (Estimated): 205
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200025
    • Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Histologically confirmed invasive breast cancer; 2. Age between 18 and 80 years; 3. cN0 breast cancer underwent radical surgery combined with Sentinel Lymph Node Dissection (SLND) alone with SLND positive or SLND and axillary lymph node dissection (ALND) with positive lymph node metastasis; 4. for SLND alone cohort, the regional lymph node irradiation area was determined according to the clinical risk model and genomic risk model assessment; 5. Ability to understand and willingness to participate the research and sign the consent form

Exclusion Criteria:

• • Pathologically positive ipsilateral supraclavicular lymph node

  • Pathologically or radiologically confirmed involvement of ipsilateral internal mammary lymph nodes;
  • Pregnant or lactating women;
  • Insulin dependent diabetes;
  • History of non-breast malignancy within 5 years with the exception of lobular carcinoma in situ, basal cell carcinoma of the skin, carcinoma in situ of skin and carcinoma in situ of the cervix;
  • patients have simultaneous contralateral breast cancer;
  • clinical diagnosis of distant metastatic disease;
  • Previous radiotherapy to the neck, chest and/or ipsilateral axillary region

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sentinel Lymph Node Dissection alone , clinical low risk group; patients treated with surgery and Sentinel Lymph Node Dissection alone with positive lymph node metastasis.	Radiation: SLND(clinical low risk); treated with whole breast irradiation(WBI)alone 50Gy/25Fx + 10Gy/5Fx or 40Gy/15Fx + 10Gy/4Fx or no PMRT
Experimental: Sentinel Lymph Node Dissection alone , clinical high risk but genomic low risk group; patients treated with surgery and Sentinel Lymph Node Dissection alone with positive lymph node metastasis.	Radiation: SLND(clinical high risk, genomic low risk); treated with whole breast irradiation(WBI)/Post-Mastectomy Adjuvant Radiotherapy(PMRT) + regional node irradiation (Axillary +supraclavicular radiotherapy),the radiation dose could be conventional radiation or hypo-fraction irradiation:50Gy/25Fx + 10Gy/5Fx or 40Gy/15Fx + 10Gy/4Fx
Experimental: Sentinel Lymph Node Dissection alone ,clinical high risk and genomic high risk group; patients treated with surgery and Sentinel Lymph Node Dissection alone with positive lymph node metastasis.	Radiation: SLND alone ,clinical high risk and genomic high risk group; treated with whole breast irradiation(WBI)/Post-Mastectomy Adjuvant Radiotherapy(PMRT) + regional node irradiation (Internal Mammary Node Irradiation+ axillary +supraclavicular radiotherapy),the radiation dose could be conventional radiation or hypo-fraction irradiation:50Gy/25Fx + 10Gy/5Fx or 40Gy/15Fx + 10Gy/4Fx
Active Comparator: with Sentinel Lymph Node Dissection(SLND) + axillary lymph node dissection(ALND); patients treated with surgery and Sentinel Lymph Node Dissection and ALND with positive lymph node metastasis.	Radiation: Sentinel Lymph Node Dissection(SLND) + axillary lymph node dissection(ALND); treated with whole breast irradiation(WBI)/Post-Mastectomy Adjuvant Radiotherapy(PMRT) + regional node irradiation (Internal Mammary Node +supraclavicular radiotherapy),the radiation dose could be conventional radiation or hypo-fraction irradiation:50Gy/25Fx + 10Gy/5Fx or 40Gy/15Fx + 10Gy/4Fx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with arm lymphedema	Incidence of ipsilateral arm lymphedema 1 year after the completion of adjuvant radiotherapy	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	Number of patients with an oncological event (local, regional and distant recurrence free survival)	5 years
Overall survival	Number of patient alive after 5 years of follow up	5-year

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: September 1, 2024
• First Submitted That Met QC Criteria: September 1, 2024
• First Posted (Actual): September 4, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2024（50）

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No