RNI Precision Trial Protocol: Optimization of Regional Node Irradiation for Sentinel Lymph Node-positive Breast Cancer Omitting Axillary Dissection Based on Clinical and Genomic Risk Assessment: A Prospective Clinical Trial

Background Sentinel lymph node biopsy (SLNB) has been the standard treatment procedure for clinically node-negative (cN0) breast cancer (BC). Three randomized trials (Z0011, AMAROS and SENOMAC) have shown that patients with low-burden sentinel lymph node metastasis can be safely omitted axillary lymph node dissection who receive adjuvant radiotherapy. However, these published studies have been insufficient to accurately assess the recurrence risk in this patient population, leading to variability in adjuvant radiotherapy volume across different studies. Objective This study evaluates whether an integrated axillary management strategy combining SLNB with individualized regional nodal irradiation (RNI) based on recurrence risk reduces 2-year lymphedema compared to ALND followed by comprehensive RNI. Materials and Methods This trial is a single institute, open-labeled, non-randomized cohort trial. Participants are stratified into two cohorts based on the extent of axillary surgery after enrollment. For SLNB cohort, patients are divided into three groups according to clinical and genomic risk assessment. Clinically high-risk patients are defined as having at least two factors (tumor size≥2cm, percent of positive SLNs>30%, LVI positive and SLN macro-metastases), who have a predicted risk of n-SLN involvement greater than 30%. Clinically high-risk n-SLN involvement patients are further detected by using RecurIndex test. For pathological node positive (pN+) after ALND cohort, patients are treated with WBI/chest wall irradiation combined with comprehensive RNI excluding the dissected axillary region; A total of 205 patients will be enrolled, with 68 patients in SLNB cohort and 137 patients in ALND cohort with a 1:2 ratio assignment. The RNI precision trial uses a clinical-genomic model to accurately stratify the recurrence risk and provides the individualized RNI volume for early-stage BC with low-burden sentinel lymph node metastasis, and we anticipate that our study will provide high-quality data to potentially support individualized RNI in this patient population.