Abstract P4-05-03: Evaluation of the prognostic accuracy of SimBioSys TumorScope in early breast cancer
Authors: Howard Frederick M. , He Gong , Pfeiffer John R , Peterson Joseph R , Cole John A. , Pearson Alexander T. , Abe Hiroyuki , Nanda Rita 
Published: March 2022

Abstract
Background: Pathological complete response (pCR) is a well validated endpoint for early-stage breast cancer (EBC) patients treated with neoadjuvant chemotherapy (NAT), with a strong correlation with long term outcomes such as event free survival (EFS) and overall survival (OS). However, given the growing armamentarium of NAT regimens, pre-treatment predictors of long-term outcome are urgently needed in order to identify patients for escalation or de-escalation of therapy. SimBioSys TumorScope (TS) is a commercially available biophysical simulation platform that utilizes baseline MRI, receptor status, and planned treatment regimen to simulate response to NACT over time. TS has demonstrated accurate prediction of pCR (accuracy &gt;90%) in prior studies. Here, we evaluate TS prediction of response as a prognostic biomarker which can be assessed prior to treatment initiation. Methods: A retrospective study was performed including patients from the University of Chicago who received NACT for EBC from Jan 2010 - March 2020. Included patients must have had a pretreatment breast MRI. TS classified patients as likely pCR/low risk of recurrence when predicted residual tumor volume was &lt; 0.01 cm3 or there was a 99.9% or greater reduction in tumor volume. Model inputs included pretreatment MRI, pathologic features from initial breast biopsy, demographic features, and treatment regimen. Models were run and predictions were recorded by investigators blinded to recurrence/pCR outcomes. The log-rank test was used to assess the prognostic value of TS predictions. Results: In total, 144 tumors from 141 patients were analyzed. Average age was 52 yrs; 65% had stage II and 19% had stage III disease; 41% had TNBC, 34% were HER2+, and 25% were HR-/HER2+. TS classified 54 tumors as having low risk of recurrence/likely pCR and 90 as having high risk of recurrence/likely residual disease. With a median follow-up of 4.7 years, 4-yr EFS was 98% in low-risk patients, and 81% for high-risk patients (hazard ratio [HR] 4.30, p = 0.01). This compared favorably to pCR as a prognostic indicator (residual disease HR for EFS 4.07, p = 0.02). Out of 94 patients who had residual disease after NAT, TS identified 10 patients as low-risk and 84 patients as high-risk - no events were seen in the low-risk group (HR not evaluable due to no events, log-rank p = 0.10). Conclusions: TS accurately predicts EFS of EBC patients treated with NAT from pre-treatment MRI and clinicopathologic data, comparable to the predictive accuracy of pCR. There was also a trend towards improved EFS among patients with residual disease predicted by TS to be low-risk. TS may have utility in the escalation/de-escalation of treatment regimens, and further evaluation in the neoadjuvant and adjuvant setting is ongoing.
Citation Format: Frederick M. Howard, Gong He, John R Pfeiffer, Joseph R Peterson, John A. Cole, Alexander T. Pearson, Hiroyuki Abe, Rita Nanda. Evaluation of the prognostic accuracy of SimBioSys TumorScope in early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-03.