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Rationale and Objectives To test the ability of quantitative measures from preoperative Dynamic Contrast Enhanced MRI (DCE-MRI) to predict, independently and/or with the Katz pathologic nomogram, which breast cancer patients with a positive sentinel lymph node biopsy will have ≥ 4 positive axillary lymph nodes upon completion axillary dissection. Methods and Materials A retrospective review was conducted to identify clinically node-negative invasive breast cancer patients who underwent preoperative DCE-MRI, followed by sentinel node biopsy with positive findings and complete axillary dissection (6/2005 – 1/2010). Clinical/pathologic factors, primary lesion size and quantitative DCE-MRI kinetics were collected from clinical records and prospective databases. DCE-MRI parameters with univariate significance (p < 0.05) to predict ≥ 4 positive axillary nodes were modeled with stepwise regression and compared to the Katz nomogram alone and to a combined MRI-Katz nomogram model. Results Ninety-eight patients with 99 positive sentinel biopsies met study criteria. Stepwise regression identified DCE-MRI total persistent enhancement and volume adjusted peak enhancement as significant predictors of ≥4 metastatic nodes. Receiver operating characteristic (ROC) curves demonstrated an area under the curve (AUC) of 0.78 for the Katz nomogram, 0.79 for the DCE-MRI multivariate model, and 0.87 for the combined MRI-Katz model. The combined model was significantly more predictive than the Katz nomogram alone (p = 0.003). Conclusion Integration of DCE-MRI primary lesion kinetics significantly improved the Katz pathologic nomogram accuracy to predict presence of metastases in ≥ 4 nodes. DCE-MRI may help identify sentinel node positive patients requiring further localregional therapy.

BackgroundWhile breast radiotherapy typically includes regional nodal basins, the treatment of the internal mammary nodes (IMN) has been controversial due to concern for long-term cardiac toxicity. For high risk patients where IMN treatment is warranted, there is limited data with regards to the degree of heart sparing conferred by modern techniques. In this study, we sought to analyze the specific heart sparing metrics conferred by deep inspiration breath hold (DIBH) in the setting of IMN irradiation.MethodsFrom 2012 to 2015, 168 consecutive patients were treated with adjuvant left-sided radiotherapy using DIBH. Retrospective review identified 49 patients who received nodal irradiation, either to a supraclavicular field (SCF) and IMN (16), or to the SCF alone (33). Cardiac mean dose and dose volumes were calculated from free breathing (FB) and DIBH treatment plans, and compared by Wilcoxon signed-rank and Mann–Whitney U tests.ResultsDIBH achieved significant reductions in mean heart dose (p < 0.001) in both the IMN treated group from 6.73 Gy to 2.79 Gy (− 56.4%) and the IMN untreated group from 4.77 Gy to 1.55 Gy (− 63.7%). There was a 7.3% difference in relative reduction that was not statistically significant (p = 0.216). Relative reductions in heart dose volume measures were all significantly lower for IMN-irradiated patients (p ≤ 0.012), with the greatest deficits at V5 that gradually diminish with increasing dose (V25).ConclusionsThe relative heart sparing benefits of the DIBH technique are retained even with IMN inclusion. However, the addition of IMN irradiation is associated with an intrinsically greater heart dose, which translates to an estimated 9.2% proportional increase in the risk of a subsequent major coronary event. In the setting of effective cardiac sparing techniques, clinicians should take these considerations into account to guide when IMN treatment is warranted.

Purpose: To determine if dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) peak enhancement (PE) of primary breast cancer can predict the presence of lymph node extracapsular extension (LNECE) in patients with axillary metastatic disease. Materials and Methods:In all, 167 patients treated with radiotherapy for invasive breast cancer from January 1, 2006 to November 1, 2007 were retrospectively identified. Patients with DCE-MRI and surgical axillary staging were included in this study. PE of primary tumors was compared according to axillary nodal status: negative, positive without LNECE, or positive with LNECE. A receiver operator characteristic curve (ROC) was plotted to determine accuracy of PE to predict LNECE.Results: Forty-six patients met the study criteria. Thirtytwo (70%) were node-negative, 9 (19%) were node-positive without LNECE, and 5 (11%) were node-positive with LNECE. PE was greater for patients with LNECE (mean 365%) compared to node-positive patients without LNECE (mean 183%) P ¼ 0.05 and node-negative patients (mean 144%) P ¼ 0.0012. Area under the ROC curve was 0.93.Conclusion: DCE-MRI PE may be a surrogate marker for LNECE. If validated, DCE-MRI may provide noninvasive kinetic information informing axillary nodal status for patients who receive chemotherapy prior to surgical axillary staging or forego axillary dissection after a positive sentinel node biopsy.

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e12540 Background: Ductal carcinoma in situ (DCIS) is a common preinvasive breast cancer typically identified on screening mammography. Pure DCIS is nonlethal, but 20-25% of DCIS cases identified on core biopsy upstage to invasive cancer at surgery and about half progress to invasive disease if not treated. As a result, most DCIS patients undergo excision and radiation therapy. DCIS score is a multigene assay that can aid in radiation treatment decision-making and serve as a surrogate marker of ipsilateral breast recurrence (IBR) risk. Breast MRI can accurately depict DCIS span and has potential to assess biology and IBR risk. We sought to assess the associations of advanced quantitative MRI features with upstaging and DCIS score. Methods: In this IRB-approved single institution prospective clinical trial, patients recommended for biopsy of calcifications or those who had residual calcifications after a biopsy yielding pure DCIS consented to receive a multiparametric breast MRI (dynamic contrast-enhanced and diffusion-weighted) prior to surgery. The following quantitative MRI features were obtained: functional tumor volume (FTV), volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), background parenchymal enhancement (BPE), and apparent diffusion coefficient (ADC). Patients with biopsy-proven DCIS were followed through completion of surgery to determine upstaging. DCIS score was performed in those with sufficient excision-proven pure DCIS. Associations of MRI features with invasive upstaging and DCIS score and were evaluated by Spearman’s correlation and the Wilcoxon rank-sum test. Results: Of the 120 patients enrolled in the study, 57 (48%) were diagnosed with pure DCIS on core biopsy. Fifty-five patients underwent surgery, 13 of whom (24%) upstaged to invasive disease. Thirty-eight pure DCIS lesions had sufficient tissue to generate a DCIS Score. Several MRI features were associated with upstaging and DCIS Score: Ktrans (p < 0.01) was significantly higher in lesions that upstaged to invasive disease. Higher DCIS scores were associated with lower Ktrans (p = 0.04) and ve (p = 0.05) values. No statistically significant associations were observed between FTV, BPE, or ADC and invasive upstaging or DCIS Score. Conclusions: This trial suggests advanced quantitative MRI features may help identify DCIS lesions at risk for upstaging to invasive disease and IBR. Specifically, an imaging feature of vascular permeability (Ktrans) showed an expected positive association with upstaging. Imaging features of vascular permeability (Ktrans and ve) showed counterintuitive inverse associations with DCIS Scores. Future research in larger cohorts is needed to validate these findings, better determine the biological reasons for these associations, and determine whether MRI features can be used clinically to optimize DCIS treatment. Clinical trial information: NCT03495011 .

e12578 Background: Ductal carcinoma in situ (DCIS) is a preinvasive breast cancer typically excised and treated with adjuvant therapy. While there is consensus that this results in overtreatment, there is little agreement on who may avoid radiation or endocrine therapy. Two freely available prediction models, Van Nuys Prognostic Index (VNPI) and Memorial Sloan Kettering Nomogram (MSK-N), are commonly used to identify low-risk DCIS based on standard clinicopathological features. Oncotype DCIS is a newer commercially available tissue-based multigene assay also used to assess risk, but its use is limited due to cost and unclear value over VNPI and MSK-N. We sought to compare these tests’ agreement in determining DCIS ipsilateral breast recurrence (IBR) risk and potential to de-escalate therapy. Methods: In this subanalysis from a prospective single center clinical trial, we analyzed 38 patients with newly diagnosed pure DCIS confirmed at excision. Each risk assessment tool presents risk in a different manner. Oncotype DCIS provides multiple assessments: a raw score (0-100), a DCIS Score Category (low, intermediate, high), and a Refined Score incorporating clinical features (10-year IBR risk). The VNPI calculates a raw score (4-12) and assigns a risk category (low, intermediate, high). MSK-N calculates a 10-year IBR risk. The tests were dichotomized as low vs. not-low risk categories using these thresholds: DCIS Score Category = low, DCIS Refined Score ≤ 10% IBR risk, VNPI risk category = low, MSK-N ≤ 10% IBR risk. Agreement of the 4 models (DCIS Score Category, DCIS Refined Score, VNPI, MSK-N) were compared using Spearman’s rank correlation for continuous data; percent agreement and Cohen’s kappa (k) were used to compare categorized data. Results: There was poor agreement of continuous risk assessments across the 4 models, with only VNPI and DCIS Refined Score showing significant but moderate correlation (r = 0.53, p = 0.001; others ranged r = 0-0.27, p > 0.1). The number of cases identified as low-risk for each assay was DCIS Score Category = 14 (37%), DCIS Refined Score = 3 (8%), VNPI = 1 (3%), and MSK-N = 0. Percent agreement of low vs. not-low risk categorizations between DCIS Refined Score, VNPI, and MSK-N was 92-97%, but each assay classified 3 or fewer cases as low-risk and kappa was not significant (k = 0-0.48, p > .1). DCIS Score Category demonstrated 63-71% agreement with the other 3 assays (k = 0-0.26). Only 1 case was classified as low-risk DCIS on multiple tests. Conclusions: DCIS risk models have poor agreement for determining IBR risk. DCIS Score Category initially identified many low-risk lesions; however, inclusion of clinical features to create a Refined Score decreased this substantially, providing very few additional low-risk cases for de-escalation over VNPI or MSK-N. Additional studies are needed to determine precise IBR rates when these models are used for adjuvant therapy decision-making. Clinical trial information: NCT03495011 .