Abstract P3-19-08: Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk?
Authors: Healy Erin , Jhawar Sachin , Beyer Sasha , White Julia R , Bazan Jose G 
Published: March 2022

Abstract
Background: Breast-cancer related lymphedema (BCRL) is a devastating treatment complication driven by the extent of axillary surgery (axillary lymph node dissection [ALND] versus sentinel lymph node biopsy [SLNB]). Regional nodal irradiation (RNI) may increase the risk of BCRL by up to 5%. Recently, investigators identified a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) as a potential organ-at-risk (OAR) demonstrating that increasing radiation dose to the ALTJ was associated with a higher risk of BCRL. Here, we set to validate whether radiation dose to the ALTJ is associated with BCRL. Materials/Methods: We identified patients with stage II-III breast cancer treated with adjuvant RNI after M or L from 2013-2018 excluding those with BCRL pre-radiation. RNI treatment planning included delineation of clinical target volumes (CTVs): breast or chest wall and regional lymph nodes per the RTOG Breast Cancer Atlas. The CTVs were expanded by 5mm to create the planning target volume (PTV). Dose delivered was 50 Gy/25 fractions with goal of 47.5 Gy (95%) to 95% of each PTV. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb &gt;2.5 cm at any 1 visit or ≥2 cm on at least 2 visits. All patients suspected of having BCRL at routine follow-up visits were evaluated by physical therapy. The ALTJ was retrospectively contoured and the following metrics collected: maximum/minimum/mean dose; V10Gy-V50Gy. Follow-up time was defined as the time from surgery to the development of BCRL or last follow-up. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. All variables with p&lt;0.10 on univariate analysis were entered in the final multivariate model (p&lt;0.05 considered statistically significant). Results: Population includes 378 patients with median age 53 years (interquartile range [IQR], 45-61 years), median body mass index (BMI) 28.4 kg/m2 (IQR, 24.3-33.4 kg/m2), 60% HR+/HER2-, 89% chemotherapy, 53% stage III, 71% underwent M, and 82% underwent ALND with median of 18 nodes removed (IQR, 11-25) and median of 2+ nodes (IQR, 1-5). Median follow-up time was 54.5 months (IQR, 40.3-72.2 months). The ALTJ and axilla PTV overlapped in 91% of the patients. BCRL developed in 97 patients (25.7%) at a median of 18.9 months (IQR, 9.9-30.6 months). The 4-year cumulative incidence of BCRL was 23.5% (26.6% ALND vs. 8.7% SLNB, p=0.002). On univariate analysis, increasing age (HR=1.02, p=.039), increasing BMI (HR=1.04, p=0.002), increasing number of nodes removed (HR=1.04, p&lt;0.0001), and use of IMRT vs. 3DCRT (HR=1.50, p=0.041) were all significantly associated with developing BCRL while increasing size of the axilla PTV (HR=0.96, p=0.047) was associated with a lower risk. None of the ALTJ metrics were associated with developing BCRL. Increasing ALTJ V45 was marginally associated with a lower risk of BCRL (HR=0.96, p=0.091). On multivariate analysis, increasing age (HR=1.02, p=0.021), increasing BMI (HR=1.04, p=0.004), and increasing number of nodes removed (HR=1.03, p=0.001) were associated with a higher risk of developing BCRL while use of IMRT (HR=1.24, p=0.338), size of the axilla PTV (HR=0.96, p=0.110) and ALTJ V45 (HR=0.99, p=0.708) were not. There were 10 local-regional recurrence (LRR) events as a first failure, 8 of which occurred with simultaneous distant metastases (DM). Of these LRRs, 5 included an axillary nodal component (all with DM) resulting in a 2.6% 4-year LRR rate (1.4% axillary recurrence rate). Conclusion: In this analysis, ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL given the low LRR and inability to validate ALTJ as an OAR.
Citation Format: Erin Healy, Sachin Jhawar, Sasha Beyer, Julia R White, Jose G Bazan. Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-08.