Boost to Unresectable Nodal Disease in Locally Advanced Breast Cancer: Outcomes and Toxicity

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<h3>Purpose/Objective(s)</h3> The supraclavicular (SCV), medial axillary and internal mammary nodes (IMNs) are not typically resected in breast cancer patients (pts). The optimal local therapy of pts with nodal disease in these regions is not well-studied. We aim to evaluate outcomes of breast cancer patients with unresected nodal disease. <h3>Materials/Methods</h3> We identified 79 pts at our institution from 2016- 2021 with unresected nodal disease in the axilla, SCV and/or IMNs defined as grossly enlarged nodes on CT, MRI or PET scan +/- biopsy confirmation. Pts were treated with breast/chest wall and regional nodal irradiation with an additional boost to the unresected nodal region. Distant failure (DF) and local-regional failure (LRF) were assessed. Kaplan-Meier was used to calculate disease-free survival (DFS), overall survival (OS) and local recurrence-free survival (LRFS). Logistic regression was used to identify variables associated with worse DFS. Acute and late toxicity of RT were evaluated. <h3>Results</h3> 33% of pts were treated with breast-conserving surgery, 65% with mastectomy and all had axillary surgery (81% ALND, 19% SLNB). 47% of pts received IMN boost (IMN), 40% axillary/SCV boost (axSCV) and 15% both IMN and axSCV boost (IMN/axSCV). Most had cT2-3 (72%), hormone receptor positive (75%), and HER-2 negative disease (84%). 57% of axSCV had cN3A disease; 84% of IMN and 83% of IMN/axSCV had cN3b disease. 7% of axSCV and 17% of IMN/axSCV had cN3c disease. Most pts received chemotherapy (97%). Median nodal boost dose was 10 Gy (range 10-20 Gy), with 17% axSCV, 22% IMN, and 17% IMN/axSCV receiving 14-20 Gy. Rates of acute and late grade 3 toxicity did not differ by boost location (acute: IMN: 20%, axSCV: 11% and IMN/axSCV 20%, <i>P</i> = 0.559; late: IMN: 40%, axSCV: 25%, IMN/axSCV: 40%, <i>P</i> = 0.630) nor by boost dose (10 Gy vs 14-20 Gy). There were no grade 4+ toxicities. With a median follow up of 30 months, the 3-year LRR, DFS, and OS was 94.5%, 86.3% and 93.8% respectively. Crude rates of failure for the entire group were 13.9% (10.1% DF; 3.8% DF+LRF). Rates of failure by boost group were axSCV: 13.3% (10% DF; 3.3% DF+LRF), IMN: 5.4% (2.7% DF, 2.7% DF+LRF), IMN/axSCV 41.7% (33.3% DF, 8.3% DF+LRF). There were no LRFs without DFs. Median time to failure was 23 months (IQR 18-34). On univariate analysis clinical tumor size (cT) and IMN/axSCV vs. IMN or axSCV alone was associated with worse DFS (HR: 9.78 95% CI 2.07-46.2, <i>P</i> = 0.004 and HR: 9.49 95% CI 2.67-33.7, <i>P</i> = 0.001). On multivariate analysis, cT approached significance (HR 6.15; 95% CI 0.95-39.8, <i>P</i> = 0.05). IMN/axSCV vs. IMN or axSCV alone retained significance (HR 4.80; 95% CI 1.27-18.13, <i>P</i> = 0.02). The difference between the axSCV vs. IMN group was not significant. <h3>Conclusion</h3> In this population of pts with unresected nodal disease, boost RT to radiographically positive LN regions can be safely delivered with low rates of grade 3+ toxicity. The majority of failures were distant with no isolated LRFs. Failures were highest in the IMN/axSCV group (∼40%). Further treatment escalation is necessary for these pts.