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Purpose: Lymphedema after regional nodal irradiation is a severe complication that could be minimized without significantly compromising nodal coverage if the anatomic region(s) associated with lymphedema were better defined. This study sought to correlate dose-volume relationships within subregions of the axilla with lymphedema outcomes to generate treatment planning guidelines for reducing lymphedema risk.Methods and Materials: Women with stage II-III breast cancer who underwent breast surgery with axillary assessment and regional nodal irradiation were identified. Nodal targets were prospectively contoured per Radiation Therapy Oncology Group guidelines for field design. The axilla was divided into 8 distinct subregions that were retrospectively contoured. Lymphedema outcomes were assessed by arm circumferences. Multivariate Cox proportional hazards regression assessed patient, surgical, and dosimetric predictors of lymphedema outcomes.Results: Treatment planning computed tomography scans for 265 women treated between 2013 and 2017 were identified. Median post-radiation therapy follow-up was 3 years (interquartile range [IQR], 1.9-3.6). Dose to the axillary-lateral thoracic vessel juncture (ALTJ; superior to level I) was most associated with lymphedema risk (maximally selected rank statistic = 6.3, P < .001). The optimal metric was ALTJ minimum dose (Dmin) <38.6 Gy (3-year lymphedema rate 5.7% vs 37.4%, P <.001), although multiple parameters relating to sparing of the ALTJ were highly correlated. Multivariate analysis confirmed ALTJ Dmin <38.6 Gy (hazard ratio [HR], 0.13; P < .001), body mass index (HR, 1.06/unit; P = .002), and number of lymph nodes removed (HR, 1.08/node; P < .001) as significant predictors. Women with ALTJ Dmin <38.6 Gy maintained median V45Gy of 99% in the supraclavicular (IQR, 94-100%), 100% in level III (IQR, 97%-100%), 98% in level II (IQR, 86%-100%), and 91% in level I (IQR, 75%-98%) nodal basins.Conclusions: Anatomic studies suggest the ALTJ region is typically traversed by arm lymphatics and appears to be an organ at risk in breast radiation therapy. Ideally, avoidance of the ALTJ may be feasible while simultaneously encompassing breast-draining nodal basins. Confirmation of this finding in future prospective studies is needed. [ABSTRACT FROM AUTHOR]

Purpose: Regional nodal irradiation for women with breast cancer is known to be an important risk factor for the development of upper extremity lymphedema, but tools to accurately predict lymphedema risks for individual patients are lacking. This study sought to develop and validate a nomogram to predict lymphedema risk after axillary surgery and radiation therapy in women with breast cancer.Methods and Materials: Data from 1832 women accrued on the MA.20 trial between March 2000 and February 2007 were used to create a prognostic model with National Cancer Institute Common Toxicity Criteria Version 2.0 grade 2 or higher lymphedema as the primary endpoint. Multivariable logistic regression estimated model performance. External validation was performed on data from a single large academic cancer center (N = 785).Results: In the MA.20 trial cohort, 3 risk factors were predictive of lymphedema risk: body mass index (adjusted odds ratio, 1.05 per unit body mass index; 95% confidence interval [CI], 1.03-1.08, P < .001), extent of axillary surgery (adjusted odds radio for 8-11 lymph nodes removed, 3.28 [95% CI, 1.53-7.89] P = .004; 12-15 lymph nodes, 4.04 [95% CI, 1.76-10.26] P = .002; ≥16 nodes, 5.08 [95% CI, 2.26-12.70] P < .001), and extent of nodal irradiation (adjusted odds radio for limited, 1.66 [95% CI, 1.08-2.56] P = .02; for extensive, 2.31 [95% CI, 1.28-4.10] P = .004). A nomogram was created from these data that predicted lymphedema risk with reasonable accuracy confirmed by both internal (concordance index, 0.69; 95% CI, 0.64-0.74) and external validation (concordance index, 0.71; 95% CI, 0.66-0.76).Conclusions: The nomogram created from the MA.20 randomized trial data using clinical information may be useful for lymphedema screening and risk stratification for therapeutic intervention trials. [ABSTRACT FROM AUTHOR]