Analysis of Predictive Factors for Arm Lymphedema Following Salvage Radiotherapy for Patients with Recurrent Breast Cancer

Objectives: This study aimed to identify clinical and dosimetric risk factors for subsequent arm lymphedema (SAL) in patients with locoregionally recurrent breast cancer who received salvage repeated radiotherapy (RT). Methods: We retrospectively analyzed 65 patients treated between 2003 and 2017. Regional nodal areas were divided into seven subregions per Gross et al. (2019) and contoured for dosimetric evaluation. Initial and repeated RT plans were deformed and merged to calculate cumulative dose-volume histograms. Equivalent dose in 2 Gy fractions (EQD2)-based parameters (max dose, mean dose, min dose, percentage of volume receving at least n Gy (VnGy)) were assessed. Optimal cut points for dosimetric parameters were determined by maximally selected rank statistics. Multivariable Cox regression and Akaike information criterion (AIC) were applied to identify predictors of SAL. Results: Salvage surgery was performed in 52% and taxane-based chemotherapy in 45%. Median accumulated prescription dose was 113.0 Gy EQD2. With a median follow-up of 30.4 months, 15 patients (23.1%) developed SAL after a median of 6.4 months. SAL was associated with taxane-based chemotherapy and higher doses to axillary-lateral thoracic junction (ALTJ) and adjacent regions. In multivariable analysis with clinical factors only, taxane-based chemotherapy was significant (HR 4.2, P=0.04). The final model with clinical and dosimetric parameters selected lateral to ALTJ V30Gy ≥60%(HR 5.35, P=0.001) plus taxane-based chemotherapy (HR 4.73, P=0.02). Conclusion: SAL occurred in 23% of patients after salvage repeated RT. Taxane-based chemotherapy and lateral to ALTJ V30 Gy ≥60% were risk factors. Applying this dose constraint and early rehabilitation referral may help reduce SAL risk.