Abstract

Determining the Organ at Risk for Lymphedema After Regional Nodal Irradiation in Breast Cancer

Jeffrey P. Gross, MD, MS,* Connor M. Lynch, BA,*Anne Marie Flores, MSPT, CLT, PhD,y,z Sumanas W. Jordan, MD, PhD,x Irene B. Helenowski, PhD,k Mahesh Gopalakrishnan, MS,* Dan Cutright, PhD,{ Eric D. Donnelly, MD,*,# and Jonathan B. Strauss, MD, MBA*,#/. Int J Radiation Oncol Biol Phys, Vol. 105, No. 3, pp. 649e658, 2019

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 posteradiation 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 Z 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; PZ .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 breastdraining nodal basins. Confirmation of this finding in future prospective studies is needed.

Main findings

• In the setting of limited axillary surgery and low-volume macroscopic nodal disease (1-3 nodes positive), adjuvant RNI with full coverage of the regional nodal targets including axillary level I is associated with low rates of both axillary recurrences and lymphedema. This is likely the case even when a portion of the ALTJ ( axillary lateral thoracic vessel juncture) region is irradiated.
• In addition to other well-known risk factors for lymphedema after breast cancer treatment, dose-volume metrics relating to superior-lateral axillary dose (eg, the ALTJ Dmin) are significantly and independently associated with lymphedema risk. Ideally, avoidance of the ALTJ may be feasible while simultaneously covering the nodal basins that drain the breast. The approach of ALTJ avoidance may be oncologically safest in women with low-volume nodal disease after a thorough dissection.