Abstract PO3-28-10: MRI Radiomic phenotypes derived from the ECOG-ACRIN E4112 Trial to assess high-risk ductal carcinoma in situ
Authors: Slavkova Kalina , Kang Ruya , Belenky Vivian , Kazerouni Anum , Biswas Debosmita , Horng Hannah , Chitalia Rhea , Hirano Michael , Xiao Jennifer , Corsetti Ralph , Javid Sarah , Spell Derrick , Wolff Antonio , Sparano Joseph , Khan Seema , Comstock Christopher , Romanoff Justin , Steingrimsson Jon , Gatsonis Constantine , Lehman Constance , Partridge Savannah , Kontos Despina , Rahbar Habib 
Published: May 2024

Abstract
INTRODUCTION Ductal carcinoma in situ (DCIS) is a non-lethal pre-invasive breast cancer that can co-exist with invasive disease. Dynamic contrast-enhanced (DCE) MRI is sensitive for the detection of high-grade DCIS and invasive cancer while Oncotype DCIS Score is a 12-gene assay that can assess recurrence risk. In practice, it is difficult to distinguish low- from high-risk DCIS, which leads to overtreatment for up to half of women diagnosed with DCIS. We hypothesize that radiomic phenotypes of DCIS derived from DCE-MRI data may serve as prognostic markers to improve risk stratification by capturing disease heterogeneity. Here we evaluate the ability of these phenotypes to predict DCIS Score and upstaging of DCIS to invasive disease on wide local excision in a multicenter trial. METHODS Data: DCE-MRI data from the ECOG-ACRIN E4112 trial were retrospectively analyzed. Primary analysis focused on participants with data on disease upstaging (N=295), with secondary analysis in a subset (N=174) of participants with DCIS Scores (dichotomized as &gt;55 and 55) and pure DCIS. Clinical information included patient demographics, lesion morphology on MRI, background parenchymal enhancement, DCIS grade, central necrosis, and hormone receptor status. Data analysis: Radiologist-drawn lesion segmentations and publicly available software, CaPTk, were used to compute 64 radiomic features from first post-contrast images for each participant. Radiomic phenotypes were identified using hierarchical clustering on the extracted features. A Chi-square test was used to evaluate the association between radiomic phenotypes and each outcome. The likelihood ratio test was used to compare two logistic regression models: 1)clinical model using only clinical information as predictors and 2) clinical+phenotypes model using clinical information and phenotype assignment as predictors. Each model was used for the prediction of upstaging to invasive disease and DCIS score. Model performance was evaluated as the 10-fold cross-validated area under the receiver operator characteristic curve (AUC). A p&lt; 0.05 was considered significant. RESULTS A total of 45 (15%) cases upstaged to invasive disease. Two radiomic phenotypes were identified: Phenotype 1 indicated greater lesion signal heterogeneity, while Phenotype 2 indicated lower heterogeneity. Radiomic phenotype was strongly associated with disease upstaging (p=0.0034) – with a higher rate of upstaging for Phenotype 1 – but not with DCIS score (p=0.1174, Table 1). For predicting disease upstaging, the clinical+phenotypes model yielded a higher AUC=0.72 and a significantly better fit to the data (p=0.0022) compared to the clinical model parameterized by clinical information alone (AUC=0.69). For predicting DCIS Score, the clinical+phenotypes model (AUC=0.77) showed similar performance compared to the clinical model (AUC=0.76) and no significant improvement in fit to the data (p=0.2920). CONCLUSION Radiomic phenotypes capturing disease heterogeneity show promise as prognostic predictors for predicting disease upstaging in DCIS compared to clinical information alone and may enable more efficient disease management. We observed that phenotypes did not have independent predictive outcome for DCIS score, suggesting that MRI and DCIS Score offer independent information and could be combined in future models to better predict disease recurrence or progression. Clinical applications of radiomic phenotypes may improve risk stratification and potentially result in decreased overtreatment of women diagnosed with DCIS.
Table 1: Association between radiomic phenotypes and DCIS outcomes using a Chi square test.
Citation Format: Kalina Slavkova, Ruya Kang, Vivian Belenky, Anum Kazerouni, Debosmita Biswas, Hannah Horng, Rhea Chitalia, Michael Hirano, Jennifer Xiao, Ralph Corsetti, Sarah Javid, Derrick Spell, Antonio Wolff, Joseph Sparano, Seema Khan, Christopher Comstock, Justin Romanoff, Jon Steingrimsson, Constantine Gatsonis, Constance Lehman, Savannah Partridge, Despina Kontos, Habib Rahbar. MRI Radiomic phenotypes derived from the ECOG-ACRIN E4112 Trial to assess high-risk ductal carcinoma in situ [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-10.