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INTRODUCTION: Breast MRI (bMRI) has become a standard of care (SOC) modality for both screening and diagnostic work-up of breast disease (1-2). Despite availability of larger bores, claustrophobia remains the most common reason for patients declining MRI (3). Anesthesia service can offer sedation during MRI improving patients’ acceptance. However, unlike routine MRI, bMRI is performed with patient positioned prone. Our anesthesiologists observed patients’ expectation of receiving general anesthesia, without understanding the risks associated with sedation/anesthesia in this particular setting and no prior trials of oral anxiolysis. OBJECTIVE: This project retrospectively reviewed bMRI exams with sedation for image quality and potential complication to identify areas for intervention such as provider education on anesthesiology risks in the bMRI environment and the implementation of an institution-approved oral anxiolysis program. METHODS: Patients receiving bMRI exams with sedation/anesthesia at a large academic cancer center were identified from the existing institutionally approved Report Imaging Quality Issue database after receiving institutional approval for this quality improvement project with waiver for consent obtained from Institution Review Board. Patient demographics, imaging data, and clinical notes were reviewed by two board certified breast radiologists with over 15 years of experience in MRI interpretation. Safety reports were reviewed in consensus between two radiologists and lead anesthesiologist for MRI department. RESULTS: Of 4844 bMRI exams, 33 were performed with sedation/anesthesia. Mean age was 60 years (range 37-77), with mean body mass index of 34 (range 21-45). Reason for anesthesia included claustrophobia in 13 (40%) patients, pain in 6 (18%), and 14 not clearly documented (42%). Eighteen of 33 (55%) exams were rated as poor quality, 7 (21%) as average, and 8 (24%) good or diagnostic. Most common reasons for poor quality included motion from snoring or pain and poor fat suppression due to body habitus. In 11/33 (33%), repeat imaging with still poor quality was documented in technologists’ comments. Length of exam appointment ranged from 52 – 155, average 90 minutes. Only one case documented facial bruising due to prone positioning and one case of positioning requiring up to 7 staff. DISCUSSION: Availability of on-site anesthesia has enabled some patients to receive bMRI. These patients present to MRI with expectation of sedation/anesthesia without understanding risks or prior trial of anxiolysis and most have a challenging body habitus contributing to difficulty in prone positioning and decreased image quality while under sedation/anesthesia. Development of an oral patient anxiolysis program and provider education may improve image quality and reduce utilization of anesthesia. Citation Format: H. T. Carisa Le-Petross, Shreyas Bhavsar, Marion E. Scoggins, Jia Sun, Thao Bui, Kyungmin Shin, Jason Stafford, Richard Carlson III, Beatriz Adrada. Safety of Breast MRI under General Anesthesia [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-05-04.

PURPOSE Triple-negative breast cancer (TNBC) is a heterogeneous disease with variable response to neoadjuvant therapy (NAT). Pathologic complete response (pCR) has become a prognostic marker for overall and disease-free survival. The aim of this study was to determine if dynamic contrast-enhanced (DCE)-MRI after 2 and/or 4 cycles of NAT can identify patients with a high likelihood of achieving pCR, triaging them to standard of care (SOC), or, when appropriate, to de-escalation trials. Conversely, we aimed to identify chemoresistant tumors that are unlikely to achieve pCR and may benefit from escalated targeted trials. METHOD AND MATERIALS 309 patients with stage I-III TNBC underwent DCE-MRI (temporal resolution: 9-12 sec) at baseline (BL), 2 cycles (C2), and 4 cycles (C4) of SOC doxorubicin/cyclophosphamide (AC) NAT as part of a prospective IRB-approved study (NCT02276443). Tumor volumes of the index lesion were calculated using 3 axis measurements during the early phase of the DCE-MRI (60s). Percent tumor volume reduction (TVR) between BL, C2, and C4 was calculated. Patients were randomly assigned to a training or a validation cohort in a 1:1 ratio. pCR was assessed at surgery after completion of SOC NAT. Correlation between pCR and TVR was evaluated using ROC analysis. RESULTS Of 309 TNBC patients, 136 (44%) achieved pCR. Following 2 cycles of NAT, TVR >80% was predictive of pCR (chemosensitivity), while TVR ≤ 55% was predictive of non-pCR (chemoresistance) with PPV 80%, NPV 89%, AUC 0.811 (0.73~0.893, p< 0.0001) in the training cohort, and PPV 82%, NPV 85%, AUC 0.815 (CI:0.736~0.894, p< 0.0001) in the validation cohort. Following 4 cycles of NAT, TVR >90% was predictive of pCR, while TVR ≤80% was predictive of non-pCR with PPV 80%, NPV 84%, AUC 0.827 (0.756~0.898, p< 0.0001) in the training cohort and with PPV 73%, NPV 82%, AUC 0.785 (CI:0.709~0.862, p< 0.001) in the validation cohort. Using this model, the pCR status was correctly classified in 50% of TNBC patients using C2 DCE-MRI in the training cohort, and 54% in the validation cohort. Only 8% were misclassified in the training cohort, and 10% in the validation cohort. Using C4 DCE-MRI, the pCR status of 61% and 57% of TNBC was correctly classified in the validation and the testing cohorts, respectively. 12% were misclassified in the validation cohort, and 21% in the testing cohort. CONCLUSION DCE-MRI after 2 and 4 cycles of AC-based NAT correctly predicted the pCR status of 54% and 57% of TNBC patients, respectively, as either excellent responders or nonresponders with high AUC 0.811 and 0.827. This may allow patients to be triaged to SOC NAT with option of de-escalation or early targeted therapies for non-responders. Citation Format: Mary S. Guirguis, Beatriz Adrada, Miral Patel, Frances Perez, Rosalind Candelaria, Wei Yang, Jia Sun, Rania M. Mohamed, Medine Boge, H. T. Carisa Le-Petross, Jessica Leung, Gary J. Whitman, Deanna L. Lane, Marion E. Scoggins, Tanya Moseley, Benjamin Musall, Jason White, Sanaz Pashapoor, Peng Wei, Jong Bum Son, Ken-Pin Hwang, Bikash Panthi, Mark Pagel, Lei Huo, Kelly K. Hunt, Elizabeth Ravenberg, Alastair M. Thompson, Jennifer K. Litton, Vicente Valero, Debu Tripathy, Stacy Moulder, Clinton Yam, Jingfei Ma, Gaiane Rauch. DCE-MRI for early prediction of excellent response versus chemoresistance in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-15.

Background: Inflammatory breast cancer (IBC) is associated with a poor prognosis. While many stage III IBC patients (pts) experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to permit subsequent surgical therapy, the prognostic significance of requiring additional NAC to enable resectability is unknown. We sought to describe the pathologic complete response (pCR) rates, breast cancer-free survival (BCFS) and overall survival (OS) among pts requiring 1 vs >1 lines of NAC prior to surgery. Methods: Upon IRB approval, pts with stage III IBC from 2 academic institutions (Dana-Farber Cancer Institute and MD Anderson Cancer Center) who received 1L or 2-3 lines (2-3L) of NAC prior to surgery were identified. Standard NAC regimens containing different drugs, such as AC-T or TCHP, were considered as 1L. Pts with locoregional progression or metastatic disease prior to surgery were excluded. Hormone receptor (HR), HER2 status, grade, and pCR, defined as no residual invasive cancer in the breast and the axilla, were evaluated. BCFS, defined as time from surgery to locoregional and/or distant recurrence, and OS, defined as time from surgery to death, were evaluated by the Kaplan-Meier method. Multivariable Cox models stratified by institution and containing the covariates pCR and tumor subtype were utilized to estimate the HR of 2-3L vs. 1L of therapy. Results: 808 eligible pts diagnosed between 1997 and 2020 were identified. 733 (91%) had 1L and 75 (9%) had 2-3L of NAC, and the median age was 50 years. 295 (37%) had HER2+, 282 (35%) HR+HER2-, 211 (26%) had HR-HER2- disease and for 20 (2%) pts, the receptor status was unknown. The median time from diagnosis to surgery was 6 months. Grade III disease, triple-negative and HER2-positive disease were more prevalent in pts receiving 2-3L of therapy (table). pCR was achieved in 178 (24%) pts receiving 1L of NAC, and in 14 (19%) pts receiving 2-3L of NAC. At 68 months of median follow-up, 417 (52%) pts experienced a recurrence with 376 in the 1L group and 41 in the 2-3L group. The 5-year BCFS was shorter for the 2-3L group compared to the 1L group (33% v 46%, HR=1.37; 95% CI:0.99-1.91). However, in 192 pts with a pCR, BCFS was similar, regardless of the number of NAC lines. There were 38 recurrences among 178 1L pts, and 3 recurrences among 14 2-3L pts, resulting in BCFS of 76% and 83% in 1L and 2-3L pts, respectively. Overall, there were 308 deaths, 276 deaths among 1L pts and 32 among 2-3L pts. The 5-yr OS estimate in 1L versus 2-3L pts was 60% versus 53% (HR=1.32, 95% CI: 0.91-1.93). Conclusion: Among pts with stage III IBC, pCR was observed among 24% who had 1L and 19% of pts who required 2-3L of NAC. BCFS and OS were comparable among pts with pCR after 1L and 2-3L. Our results suggest the need to continue to optimize current treatment strategies in IBC to improve pCR rates across all disease subtypes regardless of the number of lines of NAC required. Citation Format: Faina Nakhlis, Samuel Niman, Naoto T. Ueno, Elizabeth Troll, Sean Ryan, Eren Yeh, Laura Warren, Jennifer Bellon, Beth Harrison, Toshiaki Iwase, H. T. Carisa Le-Petross, Sadia Saleem, Mediget Teshome, Gary J. Whitman, Wendy Woodward, Beth Overmoyer, Sara Tolaney, Meredith Regan, Filipa Lynce, Rachel M. Layman. Long-term Outcomes After 1 or 2-3 Lines of Neoadjuvant Therapy in Stage III Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-14.

Background: The pathologic complete response (pCR) rate in inflammatory breast cancer (IBC) patients is worse than in non-IBC patients; new drug combinations are warranted to improve pCR rates across all IBC molecular subtypes. Based on our preclinical data, we added neratinib to standard neoadjuvant chemotherapy in both HER2+ (synergy) and HER2-/hormone receptor (HR)+ (high frequency of ERBB2 mut) untreated IBC, as a single-center, non-randomized phase I/II trial. Patients and Method: This study enrolled three cohorts: Cohort I phase Ib (C1P1B), Cohort I Phase II (C1P2) and Cohort II (C2). In C1P1B to determine the recommended phase 2 dose (RP2D), we enrolled patients with HER2+ metastatic or locally advanced breast cancer. Patients received paclitaxel/trastuzumab/pertuzumab (THP) + neratinib x 4 cycles (up to 8 cycles per physician’s discretion). For C1P2 and C2, we enrolled Stage III – IV primary IBC patients. In C1P2, patients with HER2+ IBC received neratinib (RP2D) combined with THP x 4 cycles followed by doxorubicin/cyclophosphamide (AC) x 4 cycles. Per stage I design, 11 patients were enrolled with plan to enroll 20 more patients in Stage II if at least 6 had a pCR. In C2, patients with HER2-/HR+ IBC received neratinib 200 mg/day combined with paclitaxel x 4 cycles followed by AC x 4 cycles. Stage I design planned for enrollment of 16 patients with enrollment of 15 more patients on stage II, if at least 2 Stage I patients had pCR. In all three cohorts, patients initiated prophylactic anti-diarrheal medication (loperamide & budesonide) with the first dose of neratinib. Results: From 2018 to 2022, thirty-four patients were enrolled and treated (n=4 C1P1B, n=14 C1P2, n=16 C2). In C1P1B, observed DLTs (dose limiting toxicities) were Grade (Gr) 2 Diarrhea, n=2 (50%); Gr3 diarrhea, n=2 (50%); 2 patients had a serious adverse event (SAE); 3 patients (55%) had Gr2 nausea. The RP2D was established at 80 mg/day (dose level 0). For patients in C1P2, the most frequently occurring adverse events (AEs) included Gr2 Alopecia, n=14 (100%); Gr2&3 Diarrhea, n=14 (100%); Gr2/3 Nausea, n=12 (86%); Gr2/3 Anemia, n=7 (50%); Gr2/3 Fatigue, n=8 (57%); Gr2/3 Hypokalemia, n=6 (57%); and Gr2/3 Neutrophil count decreased, n= 7 (50%). 6 patients had an SAE. Of the first 11 patients, 5 (46%) had pCR, 1 (9%) RCB-1, 1 (9%) RCB-II and 1 (9%) RCB-III. Three patients stopped study treatment for toxicity (27%), were non-evaluable and replaced. Of these, one had RCB-III (33.3%), one progression of disease (PD) (33.3%), and one came off study for toxicity (33.3%). Rather than replacing additional non-evaluable patients, the study was closed to new patient accrual. In C2, the most frequently occurring AEs were Gr2 diarrhea, n=7(44%); Gr3 diarrhea, n=8 (50%); Gr2 alopecia, n=14 (88%); Gr2/3 Anemia, n=10 (63%); Gr2/3 Nausea, n=7 (44%); Gr2/3 Neutropenia, n= 7 (44%). 3 patients had an SAE. Of 16 patients in this cohort, 1 had pCR (6%), 5 RCB-II (31%), 4 RCB-III (25%), 3 came off study for toxicity (19%) and 3 had PD (19%). C2 also closed to new patient accrual given the high toxicity profile. Conclusion: The addition of neratinib did not improve the pCR rate in HER2+ or HER2-/HR+ subtypes of IBC, and increased toxicities were observed. The trial closed to new patient entry March 2022. However, some patients achieved significant response. Biomarker analysis is ongoing. Evaluable participants will continue long-term follow-up per protocol. Acknowledgments: This study is supported by PUMA Biotechnology. Citation Format: Angela N. Marx, Megumi Kai, Min Fu, Hope E. Murphy, Jie S. Willey, Huiming Sun, Angela Alexander, Roland L. Bassett, Gary J. Whitman, H. T. Carisa Le-Petross, Miral Patel, Banu K. Arun, Sausan Abouharb, Parijatham S. Thomas, Carlos H. Barcenas, Nuhad K. Ibrahim, Vicente Valero, Naoto T. Ueno, Rachel M. Layman, Bora Lim, Wendy Woodward, Anthony Lucci. A phase 1b study of neratinib with THP in metastatic and locally advanced breast cancer, and phase II study of THP followed by AC in HER2 + primary inflammatory breast cancer (IBC), and neratinib with taxol followed by AC in HR+/HER2- IBC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-09.

PURPOSE Triple negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer. Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) predicts better survival. Early prediction of the treatment response can potentially triage non-responding patients to alternative protocol treatments, spare them of the unneeded toxicity, and improve pCR. We evaluated the ability of radiomic textural analysis of intratumoral and peritumoral regions on the dynamic contrast enhanced (DCE) and diffusion-weighted imaging (DWI) MRI images obtained early during NAST to predict pCR. MATERIALS AND METHODS This IRB-approved prospective study (NCT02276443) included 182 patients with biopsy proven stage I-III TNBC who had multiparametric MRIs at baseline (BL), post 2 cycles (C2), and post 4 cycles (C4) of NAST before surgery. Tumors and peritumoral regions of 5 mm and 10 mm in thickness were segmented on the 2.5 minutes DCE subtraction images and on the b=800 DWI images. Ten histogram-based first order texture features including mean, minimum, maximum, standard deviation, kurtosis, skewness, 1st, 5th, 95th, and 99th percentile, and 300 radiomic Grey Level Co-occurrence matrix (GLCM) features along with their absolute and relative differences between the 3 imaging time points were extracted from the tumors and from the peritumoral regions with an in-house Matlab toolbox. Treatment response at surgery (pCR vs non-pCR) was documented. The samples were divided into training and testing datasets by a 2:1 ratio. Area under the receiver operating characteristics curve (AUC ROC) was calculated for univariate analysis in predicting pCR. Logistic regression with elastic net regularization was performed for texture feature selection. Parameter optimization was performed by using 5-fold cross-validation based on mean cross-validated AUC in the training set. RESULTS Of 182 TNBC patients, 88 (48%) had pCR and 94 (52%) did not achieve pCR. Eight multivariate models combining radiomic features from both DCE and DWI tumoral and peritumoral regions had AUC > 0.8 (0.807-0.831) with p-value < 0.001 in both training and testing sets. The highest AUC=0.831 was obtained from a model consisting of 15 radiomic features: tumor DWI (5 GLCM features) at C2, peritumoral region on DCE (skewness) at C2, tumor DCE (1st, 5th percentile) at C4, tumor DWI (3 GLCM features) at C4, peritumoral region DWI (1 GLCM feature) at C4, and the relative difference between C4/C2 on DCE (5th, 95th percentile and mean). CONCLUSION Multi-parametric MRI-based radiomics models from the tumor and the peritumoral regions showed high accuracy as potential early predictors of NAST response in TNBC patients. Citation Format: Rania M. Mohamed, Bikash Panthi, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, Miral Patel, Nabil Elshafeey, Sanaz Pashapoor, Zijian Zhou, Jong Bum Son, Ken-Pin Hwang, H. T. Carisa Le-Petross, Jessica Leung, Marion E. Scoggins, Gary J. Whitman, Zhan Xu, Deanna L. Lane, Tanya Moseley, Frances Perez, Jason White, Elizabeth Ravenberg, Alyson Clayborn, Mark Pagel, Huiqin Chen, Jia Sun, Peng Wei, Alastair M. Thompson, Stacy Moulder, Anil Korkut, Lei Huo, Kelly K. Hunt, Jennifer K. Litton, Vicente Valero, Debu Tripathy, Clinton Yam, Jingfei Ma, Gaiane Rauch. Multi-Parametric MRI-Based Radiomics Models from Tumor and Peritumoral Regions as Potential Predictors of Treatment Response to Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-06.

Background and Purpose Triple negative breast cancer (TNBC) is a biologically aggressive tumor and a refractory subtype of breast cancer due to the lack of therapeutic targets, such as estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. In this study, we investigated the accuracy of radiomic models based on the dynamic contrast enhanced (DCE) MRI images obtained after the completion of NAST as discriminators of treatment response in TNBC patients. Materials and Methods This IRB-approved prospective study (ARTEMIS trial, NCT02276443) included 181 patients with biopsy proven stage I-III TNBC who Had MRIs after completion of NAST and before surgery. Patients were classified as pathologic complete response (pCR) and non-pCR at the surgery. Tumors were segmented on the 2.5 minutes DCE subtraction images. Regions with necrosis or clip artifacts were excluded from the contour. If tumors were not visible, the tumor bed was contoured. Whole-tumor histogram-based first order texture features (p=10) including mean, minimum, maximum, Standard deviation, kurtosis, skewness, 1st, 5th, 95th, and 99th percentiles, and radiomic (p=300) Grey Level Co-occurrence matrix (GLCM) features were extracted with an in-house Matlab toolbox. The samples were split into training and testing data sets by a 2:1 ratio. For univariate analysis area under the receiver operating characteristics curve (AUC ROC) was performed for pCR status prediction. For texture feature selection logistic regression with elastic net regularization was performed. Parameter optimization was performed by using 5-fold cross-validation based on mean cross-validated AUC in the training set. A P-value less than 0.05 was considered statistically significant. Results Of the total 181 patients, 88 (49%) had pCR and 93 (51%) had non-pCR. Univariate analysis identified 7 statistically significant first order imaging features (Minimum, Maximum, Mean, 1st Percentile, 5th Percentile, 95th Percentile, and 99th Percentile) with AUC >= 0.7 (p< 0.001), in both training and testing data sets. Percentile 5 showed highest AUC = 0.78 (p< 0.001). Two multivariate models were statistically significant at cross-validation with AUC>=0.7. The first model combined 2 first order data (Percentile 1 and Percentile 5) with AUC = 0.73 (p< 0.001). The second model combined 8 first order features (Percentile 1, 5, 95, 99, Mean, Minimum, Maximum, and Skewness) and 24 GLCM features with AUC = 0.7 (p=0.003). Conclusion DCE-MRI radiomic features from tumor and tumor bed regions in TNBC may be helpful imaging biomarkers for predicting treatment response after NAST. Citation Format: Rania M. Mohamed, Bikash Panthi, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, Miral Patel, Nabil Elshafeey, Sanaz Pashapoor, Zijian Zhou, Jong Bum Son, Ken-Pin Hwang, H. T. Carisa Le-Petross, Jessica Leung, Marion E. Scoggins, Gary J. Whitman, Zhan Xu, Deanna L. Lane, Tanya Moseley, Frances Perez, Jason White, Huiqin Chen, Jia Sun, Peng Wei, Jennifer K. Litton, Vicente Valero, Clinton Yam, Mark Pagel, Jingfei Ma, Gaiane Rauch. A Pre-operative Dynamic Contrast Enhanced MRI-Based Radiomics Models as Predictors of Treatment Response after Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-35.

Background and Purpose Early prediction of neoadjuvant systemic therapy (NAST) response in triple negative breast cancer (TNBC) patients could potentially aid in the selection of alternative therapies and avoid unnecessary toxicity in patients unlikely to achieve pathologic complete response (pCR) with NAST. In this study, we investigated the radiomic features of the peritumoral and the tumoral regions from dynamic contrast enhanced (DCE) MRI acquired at different time points of NAST for early treatment response prediction in TNBC. Methods and Materials This study included 182 biopsy-confirmed stage I-III TNBC patients enrolled in an IRB approved prospective clinical trial (NCT02276433). All patients underwent DCE-MRI on a GE 3T MRI scanner at baseline (BL), after two (C2) and four (C4) cycles of doxorubicin/cyclophosphamide based chemotherapy and before surgery. The peritumoral and the tumoral regions were segmented manually by two fellowship-trained radiologists using early phase (2.5 min) DCE-MRI subtraction images. Ten first order radiomic features, 300 grey-level-co-occurrence matrix (GLCM) features along with their absolute and relative differences (C4/BL, C2/BL, C4/C2) between the 3 imaging time points were extracted from the peritumoral and the tumoral regions. Patients were randomly divided into training and testing sets in a 2:1 ratio. For univariate analysis, area under the receiver operating characteristics curve (AUC ROC) was measured to determine the features most predictive of pCR/non-pCR. Wilcoxon Rank Sum test was used to test the statistical significance of predictive performance. In multivariate analysis, radiomic models were established using logistic regression with elastic net regularization followed by 5-fold cross validation for performance assessment. Results Eighty-eight (48%) patients had pCR (59 training, 29 testing) and 94 (52%) patients had non-pCR (63 training, 31 testing). Twenty-five radiomic features (4 from peritumoral C4, 5 from tumoral C4, 4 from peritumoral C4/BL, 6 from tumoral C4/BL, 2 from peritumoral C4/C2 and 4 from tumoral C4/C2) were statistically significant with AUC ≥ 0.75 in both the training and the testing sets at the univariate analysis. The significant features at C4 had AUCs of 0.75-0.79 for the training set and 0.76-0.81 for the testing set. Changes measured between C4 and BL or C2 showed AUC of 0.76-0.84 in the training and 0.75-0.81 in the testing datasets. Eleven multivariate regression models comprised of radiomic features at BL, C2, C4 and their changes (C4/BL, C4/C2 and C2/BL) showed an AUC of 0.80-0.84 for cross validation and an AUC of 0.80-0.82 for independent testing. Conclusions Radiomic models using longitudinal DCE MRI parameters of peritumoral and tumoral regions during NAST have the potential to predict pCR in TNBC patients undergoing NAST. Citation Format: Bikash Panthi, Rania M. Mohamed, Beatriz Adrada, Rosalind Candelaria, Mary S. Guirguis, Wei Yang, Medine Boge, Miral Patel, Nabil Elshafeey, Sanaz Pashapoor, Zijian Zhou, Jong Bum Son, Ken-Pin Hwang, H. T. Carisa Le-Petross, Jessica Leung, Marion E. Scoggins, Gary J. Whitman, Zhan Xu, Deanna L. Lane, Tanya Moseley, Frances Perez, Jason White, Elizabeth Ravenberg, Alyson Clayborn, Mark Pagel, Huiqin Chen, Jia Sun, Peng Wei, Alastair M. Thompson, Stacy Moulder, Anil Korkut, Lei Huo, Kelly K. Hunt, Jennifer K. Litton, Vicente Valero, Debu Tripathy, Clinton Yam, Jingfei Ma, Gaiane Rauch. Longitudinal DCE-MRI Radiomic Models for Early Prediction of Response to Neoadjuvant Systemic Therapy (NAST) in Triple Negative Breast Cancer (TNBC) Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-34.

Introduction COMET (Comparing an Operation to Monitoring, with or without Endocrine Therapy) is a phase III clinical trial randomizing patients diagnosed with low-intermediate grade DCIS to either active monitoring or surgery. The study has a planned accrual goal of 1200 patients and is enrolling until 12/31/22. The protocol requires agreement between two pathologists (who do not need to be at the same institution) that a case fulfills COMET eligibility criteria. If there is disagreement, a third pathology review is required. As per protocol, tissue blocks or unstained slides of biopsies containing DCIS from enrolled patients are sent to a designated central location. While central pathology review is not a pre-requisite of the study, a retrospective review of received materials was performed to determine adequacy for correlative molecular and spatial profiling studies. Methods Sites submit either a tissue block or twenty (20) sequentially numbered, unstained, serial five-micron tissue sections from a diagnostic biopsy of DCIS to the Alliance Foundation Trials (AFT) central biorepository, a CAP-accredited biobank. All submitted biospecimens are de-identified (coded) and investigators are blinded to arm assignment and primary study outcomes. To evaluate the adequacy of specimens for subsequent correlative science studies, one unstained slide from each submitted slide set was stained with routine hematoxylin and eosin by the biobank, scanned at 40X magnification with an Aperio scanner, and provided to one of two expert breast pathologists for adequacy review. Slides were rated as “DCIS present”, “DCIS absent”, or “possible DCIS.” To conserve tissue, submitted tissue blocks are held in abeyance pending future correlative science planning. Results As of May 2022, tissue has been submitted from 789 of 856 eligible patients enrolled in the trial, demonstrating a very high level (92%) of case submission compliance. Despite the limiting size of such lesions and general clinical center hesitancy to release blocks for clinical trial research, tissue blocks were received from 376 of 789 (48%) of cases. Among 359 cases involving slide-only submissions that have been retrospectively reviewed to date, 294 were definite DCIS (82%), 25 (7%) were classified as possible DCIS, and 40 cases (11%) were classified as no DCIS present in the section reviewed. In no case was high grade DCIS or invasive breast cancer observed. Of the cases considered possible DCIS, atypical cells were present, but the lesions were too small or incomplete to confirm DCIS. The small percentage of cases that lacked DCIS or definite DCIS could be attributed to the receipt of a different block or subsequent (deeper) section from the same block used for the initial diagnosis. These cases were previously known to the submitting institutions. Conclusion Interim analysis at 71% accrual demonstrates both the feasibility of obtaining diagnostic biopsy material of limited size and the adequacy of these samples for subsequent correlative science studies that aim to improve pathology diagnostics and patient management. Citation Format: Rachel Factor, Stuart Schnitt, Robert West, Terry Hyslop, Thomas Lynch, Deborah Collyar, Desiree Basila, Lars Grimm, Lorraine King, Jeffrey Marks, Sunil Badve, Mark Watson, Marc Ryser, Anna Weiss, Anna Rapperport, Linda McCall, H. T. Carisa Le-Petross, Ann Partridge, E Shelley Hwang, Alastair M. Thompson. Centralized adequacy assessment of ductal carcinoma in situ samples for the COMET study (AFT-25) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-13.