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

Breast cancer-related lymphedema (BCRL) is a disabling late complication after postmastectomy radiotherapy (PMRT), particularly in patients who undergo axillary lymph node dissection (ALND). The axillary–lateral thoracic vessel junction (ALTJ), an anatomically defined lymphatic–functional substructure, may represent a relevant residual lymphatic drainage site after surgery. We aimed to evaluate whether the radiation dose to the ALTJ can predict BCRL and to develop predictive models for individualized risk estimation. A total of 271 patients treated with PMRT from 2019 to 2022 comprised 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 feature selections followed by multivariable logistic regression, and a Cox regression–based nomogram was constructed using multimethod consensus feature selection. Both models were evaluated and validated without refitting in the temporal cohort. The 2-year cumulative BCRL incidence was 25.1% in the development cohort and 22.2% in the validation cohort. Multivariate analysis revealed that the number of dissected lymph nodes (LNDno) and ALTJ V30 were 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 preliminary risk stratification system was developed using thresholds of LNDno > 13 and ALTJ V30 > 51.75%, categorizing patients into 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 the ALTJ V25, V30, V35, and Dmean, achieved C-indices of 0.948 and 0.894 in the development and validation cohorts, respectively. This study reveals that the ALTJ V30 and surgical extent are important predictors of BCRL in postmastectomy patients receiving radiotherapy. These findings support the consideration of the ALTJ as a quantifiable lymphatic-functional substructure relevant to BCRL risk and suggest that an ALTJ V30 < 51.75% is an exploratory planning threshold that requires external validation. The NTCP model and nomogram may assist individualized risk estimation and risk-adapted surveillance.