Identifying the Axillary Substructure at Risk for Lymphedema in Operable Patients With Breast Cancer Receiving Regional Nodal Irradiation.

PURPOSE: Axillary substructures may contribute to the development of breast cancer-related lymphedema (BCRL). This study aimed to compare dose-volume parameters of various substructures to identify high-risk regions associated with BCRL and to evaluate the clinical applicability of these findings. METHODS AND MATERIALS: Cohort-Initial included 336 patients with pT1-3N0-1M0 breast cancer who underwent mastectomy or lumpectomy with axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) between August 2018 and February 2021. The Norman questionnaire was used to assess BCRL. Thirteen dose-volume parameters across 8 axillary substructures were assessed for association with BCRL. Cohort-Recurrence comprised 50 consecutive ALND-treated patients with regional nodal recurrence diagnosed using positron emission tomography/computed tomography, used to evaluate the recurrence risk in the candidate substructures. Cohort-Reoptimization involved 20 patients from the Cohort-Initial who received excessive radiation doses in the candidate substructure. Their treatment plans were reoptimized to assess the feasibility of dose reduction while maintaining target coverage and organ dose. RESULTS: The patient-reported cumulative incidence of BCRL was 33.9% during a median follow-up of 60 months. Significant baseline risk factors included body mass index ≥ 27.18 kg/m2, tumor size ≥ 1.9 cm, premenopausal status, and ≥ 18 lymph nodes removed (all P < .05). The most significant dosimetric parameter was axillary-lateral thoracic vessel juncture (ALTJ)-V35Gy ≥ 79.2%. A predictive nomogram incorporating these clinicopathologic factors and the ALTJ parameter was developed with reasonable accuracy, as confirmed by self-training (area under the curve value, 0.780) and internal validation (area under the curve value, 0.769). None of the 196 fluorodeoxyglucose-avid regional nodes in Cohort-Recurrence were located within the ALTJ. Reoptimization of ALTJ-V35Gy was feasible without compromising the radiation therapy plan quality. CONCLUSIONS: ALTJ-V35Gy < 79.2% may serve as a recommended dose constraint for patients undergoing RNI after ALND. Avoiding excessive radiation to the ALTJ is clinically feasible and safe, potentially mitigating BCRL risk without compromising dose coverage to high-risk nodal regions.