Dose to the axillary-lateral thoracic vessel junction predicts breast cancer-related lymphedema after postmastectomy radiotherapy: development and temporal validation of NTCP and Nomogram models

Background Breast cancer-related lymphedema (BCRL) is a disabling late complication after postmastectomy radiotherapy (PMRT). This study evaluated the axillary-lateral thoracic vessel junction (ALTJ) as a functional organ-at-risk (OAR), established its dose-response relationship with BCRL, and developed validated predictive models to guide individualized risk mitigation. Methods 271 patients treated with PMRT from 2019 to 2022 constituted the development cohort, and 45 independent patients treated in 2023 formed the temporal validation cohort. All patients underwent modified radical mastectomy. The ALTJ was contoured on planning CT according to Gross et al. Candidate clinical factors and ALTJ dose–volume histogram (DVH) parameters were analyzed. A normal tissue complication probability (NTCP) model was developed using LASSO-based screening followed by multivariable logistic regression, and a Cox regression–based nomogram was built using multi-method consensus feature selection. Both models were evaluated and validated without refitting in the temporal cohort. Results The 2-year cumulative BCRL incidence was 25.1% in the development and 22.2% in the validation cohort. Multivariable analysis identified the number of dissected lymph nodes (LNDno) and ALTJ V30 as the strongest predictors. The final NTCP model achieved an AUC of 0.816 in the development cohort and 0.860 in the validation cohort, with Brier scores of 0.135 and 0.111, respectively. A clinically actionable risk stratification system was derived using thresholds of LNDno > 13 and ALTJ V30 > 51.75%, identifying high-, moderate-, and low-risk groups with 2-year BCRL rates of 58.8%/54.5%, 26.4%/18.2%, and 5.3%/0% in the development and validation cohorts, respectively. A nomogram, integrating LNDno with ALTJ V25, V30, V35, and Dmean, achieved C-indices of 0.948 and 0.894 in the two cohorts, respectively. Conclusions This study identifies ALTJ V30 and surgical extent as important predictors of BCRL in postmastectomy patients receiving radiotherapy. The findings support the consideration of ALTJ as a quantifiable OAR and provide an evidence-based dose–volume constraint (V30 < 51.75%). The validated NTCP model and nomogram offer practical tools for individualized risk estimation and may inform targeted surveillance and preventive strategies.