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Recurrent or new primary breast cancer with an indication for comprehensive regional nodal irradiation (RNI) in the setting of prior radiotherapy (RT) to the supraclavicular area (SCV) and upper axilla presents a unique treatment challenge due to cumulative brachial plexus (BP) dose tolerance. Brachial plexopathy is a debilitating potential consequence of RT, and BP dose monitoring is needed for comprehensive reirradiation (reRT). We hypothesize that pencil beam scanning proton therapy (PBS-PT) and photon volumetric-modulated arc therapy (VMAT) are conformal techniques that allow BP relative dose-sparing, while maintaining target volume (TV) dose. A comparative evaluation was performed to assess each approach. In this IRB-approved retrospective study, all patients with ipsilateral recurrent or new primary breast cancer previously treated with photon RT, then receiving PBS-PT reRT to TV with at least partial BP overlap, were identified. VMAT plans were developed by photon breast dosimetrists using matched individualized BP dose constraints (BP maximum 17.1-53.9 Gy) used in the PBS-PT course. BP and TV DVH parameters were assessed. Patient and tumor characteristics, treatment parameters, clinical outcomes, and toxicities were collected. The median follow-up from the start of reRT was 10.5 months. Ten consecutive patients were identified. Median patient age was 58 years (41-82), with median time between RT courses of 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (42.6-60.0), 50.4 Gy(RBE) (45.0-64.4), and 102.4 Gy(RBE) (95.0-120.0), respectively. PBS-PT and VMAT plans matched BP doses, with the median maximum and mean BP cumulative doses 86.6 Gy (RBE) and 60.7 Gy (RBE) for PBS-PT and 87.5 Gy and 60.2 Gy for VMAT, respectively. TV coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were generally lower for VMAT vs. IMPT plans: axilla level II were 84.8%, 91.8%, and 75.7% vs. 90.9% (p=0.17), 88.3% (p=0.04), and 84.5% (p<0.01); axilla level III were 89.8%, 75.1%, and 64.0% vs. 95.4% (p=0.39), 91.8% (p=0.12), and 86.5% (p=0.32); and SCV were 83.0%, 74.3%, and 67.2% vs. 90.9% (p=0.41), 82.1% (p=0.13), and 68.2% (p=0.76), respectively. One patient developed symptoms of brachial plexopathy with neuropathy in the ulnar nerve distribution without pain or weakness. This patient had the highest maximum cumulative BP dose of the entire cohort (106.1 Gy(RBE)). VMAT and PBS-PT provide conformal RT plans that can provide BP dose sparing but some surrounding compromise of the adjacent TV at risk. In this cohort, PBS-PT improved BP sparing and TV coverage versus VMAT. Further study with uniform TV and prescription parameters will be useful for direct comparison of the two modalities as the approach to this clinical situation continues to be refined. Longer follow-up will be needed to characterize the implication of cumulative BP dose on risk of developing clinically-significant brachial plexopathy. [ABSTRACT FROM AUTHOR]

Intravascular tumor emboli in axillary soft tissue (ITE) is a rare pathologic finding in breast cancer and is associated with higher axillary nodal disease burden. The independent prognostic and predictive value of this biomarker is unknown, as is the role of radiotherapy for ITE. We analyzed breast cancer patients treated at our institution from 1992-2020, excluding those over 90 years of age at diagnosis, primary tumors >5cm in size, receipt of neoadjuvant chemotherapy, or those with synchronous bilateral breast cancers. A 1:3 propensity score match was performed between patients with ITE and those without. Matching was based on age, pathologic T stage, number of positive nodes removed, receipt of radiotherapy or chemotherapy, and biologic subtype. Disease free survival (DFS) was evaluated using a Cox regression analysis. Locoregional recurrence (LRR) and distant recurrence were evaluated using competing risks methods. These endpoints were compared between patients with versus without ITE. Among those with ITE, we evaluated whether radiotherapy (RT) improved outcomes using the same methods with a six-month landmark. We identified 127 patients with ITE, of whom, 103 (81%) were propensity score matched to 309 without ITE. Median follow up from surgery was 6.9 years (IQR 2.5, 10). 5-year DFS for those with ITE was 68% (95% CI 57%-82%) versus 78% (95% CI 73%-84%) for those without ITE (HR 1.37, 95% CI 0.82-2.30, p = 0.2). ITE was associated with increased likelihood of distant recurrence (p=0.02; 5-year cumulative incidence 26%, 95% CI 16%-38% and 14%, 95% CI 10%, 19%, respectively), but was not associated with LRR (p=0.97; 5-year cumulative incidence 5.4%, 95% CI 1.3%-14% and 8.7%, 95% CI 5.6%-12%, respectively). Among those with ITE, 5-year DFS was 74% (95% CI 63%-87%) for those receiving RT versus 32% (95% CI 10%-98%) among those not receiving RT (HR 0.33, 95% CI 0.12-0.91, p=0.03). Patients with intravascular tumor emboli in axillary soft tissue exhibited higher rates of distant recurrence compared to a propensity score matched control group. Among patients with ITE, those who received RT demonstrated improved DFS. [ABSTRACT FROM AUTHOR]