MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Authors

Chengyue Wu
Angela M Jarrett
Zijian Zhou
Nabil Elshafeey
Beatriz E Adrada
Rosalind P Candelaria
Rania M M Mohamed
Medine Boge
Lei Huo
Jason B White
Debu Tripathy
Vicente Valero
Jennifer K Litton
Clinton Yam
Jong Bum Son
Jingfei Ma
Gaiane M Rauch
Thomas E Yankeelov

Publication Date

9-16-2022

Journal

Cancer Research

Abstract

Triple-negative breast cancer (TNBC) is persistently refractory to therapy, and methods to improve targeting and evaluation of responses to therapy in this disease are needed. Here, we integrate quantitative MRI data with biologically based mathematical modeling to accurately predict the response of TNBC to neoadjuvant systemic therapy (NAST) on an individual basis. Specifically, 56 patients with TNBC enrolled in the ARTEMIS trial (NCT02276443) underwent standard-of-care doxorubicin/cyclophosphamide (A/C) and then paclitaxel for NAST, where dynamic contrast-enhanced MRI and diffusion-weighted MRI were acquired before treatment and after two and four cycles of A/C. A biologically based model was established to characterize tumor cell movement, proliferation, and treatment-induced cell death. Two evaluation frameworks were investigated using: (i) images acquired before and after two cycles of A/C for calibration and predicting tumor status after A/C, and (ii) images acquired before, after two cycles, and after four cycles of A/C for calibration and predicting response following NAST. For Framework 1, the concordance correlation coefficients between the predicted and measured patient-specific, post-A/C changes in tumor cellularity and volume were 0.95 and 0.94, respectively. For Framework 2, the biologically based model achieved an area under the receiver operator characteristic curve of 0.89 (sensitivity/specificity = 0.72/0.95) for differentiating pathological complete response (pCR) from non-pCR, which is statistically superior (P < 0.05) to the value of 0.78 (sensitivity/specificity = 0.72/0.79) achieved by tumor volume measured after four cycles of A/C. Overall, this model successfully captured patient-specific, spatiotemporal dynamics of TNBC response to NAST, providing highly accurate predictions of NAST response.

Significance: Integrating MRI data with biologically based mathematical modeling successfully predicts breast cancer response to chemotherapy, suggesting digital twins could facilitate a paradigm shift from simply assessing response to predicting and optimizing therapeutic efficacy.

Keywords

Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cyclophosphamide, Doxorubicin, Female, Humans, Magnetic Resonance Imaging, Neoadjuvant Therapy, Paclitaxel, Treatment Outcome, Triple Negative Breast Neoplasms

DOI

10.1158/0008-5472.CAN-22-1329

PMID

35914239

PMCID

PMC9481712

PubMedCentral® Posted Date

3-16-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes