MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens

Abstract We developed a practical framework to construct digital twins for predicting and optimizing triple-negative breast cancer (TNBC) response to neoadjuvant chemotherapy (NAC). This study employed 105 TNBC patients from the ARTEMIS trial (NCT02276443, registered on 10/21/2014) who received Adri...

Full description

Saved in:
Bibliographic Details
Main Authors: Chengyue Wu, Ernesto A. B. F. Lima, Casey E. Stowers, Zhan Xu, Clinton Yam, Jong Bum Son, Jingfei Ma, Gaiane M. Rauch, Thomas E. Yankeelov
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:npj Digital Medicine
Online Access:https://doi.org/10.1038/s41746-025-01579-1
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850145364446806016
author Chengyue Wu
Ernesto A. B. F. Lima
Casey E. Stowers
Zhan Xu
Clinton Yam
Jong Bum Son
Jingfei Ma
Gaiane M. Rauch
Thomas E. Yankeelov
author_facet Chengyue Wu
Ernesto A. B. F. Lima
Casey E. Stowers
Zhan Xu
Clinton Yam
Jong Bum Son
Jingfei Ma
Gaiane M. Rauch
Thomas E. Yankeelov
author_sort Chengyue Wu
collection DOAJ
description Abstract We developed a practical framework to construct digital twins for predicting and optimizing triple-negative breast cancer (TNBC) response to neoadjuvant chemotherapy (NAC). This study employed 105 TNBC patients from the ARTEMIS trial (NCT02276443, registered on 10/21/2014) who received Adriamycin/Cytoxan (A/C)-Taxol (T). Digital twins were established by calibrating a biology-based mathematical model to patient-specific MRI data, which accurately predicted pathological complete response (pCR) with an AUC of 0.82. We then used each patient’s twin to theoretically optimize outcome by identifying their optimal A/C-T schedule from 128 options. The patient-specifically optimized treatment yielded a significant improvement in pCR rate of 20.95–24.76%. Retrospective validation was conducted by virtually treating the twins with AC-T schedules from historical trials and obtaining identical observations on outcomes: bi-weekly A/C-T outperforms tri-weekly A/C-T, and weekly/bi-weekly T outperforms tri-weekly T. This proof-of-principle study demonstrates that our digital twin framework provides a practical methodology to identify patient-specific TNBC treatment schedules.
format Article
id doaj-art-7ab5eeb4990f42929d7faf65df8c8c1c
institution OA Journals
issn 2398-6352
language English
publishDate 2025-04-01
publisher Nature Portfolio
record_format Article
series npj Digital Medicine
spelling doaj-art-7ab5eeb4990f42929d7faf65df8c8c1c2025-08-20T02:28:07ZengNature Portfolionpj Digital Medicine2398-63522025-04-018111310.1038/s41746-025-01579-1MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimensChengyue Wu0Ernesto A. B. F. Lima1Casey E. Stowers2Zhan Xu3Clinton Yam4Jong Bum Son5Jingfei Ma6Gaiane M. Rauch7Thomas E. Yankeelov8 Department of Imaging Physics, The University of Texas MD Anderson Cancer CenterOden Institute for Computational Engineering and Sciences, The University of Texas at AustinOden Institute for Computational Engineering and Sciences, The University of Texas at Austin Department of Imaging Physics, The University of Texas MD Anderson Cancer CenterDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center Department of Imaging Physics, The University of Texas MD Anderson Cancer Center Department of Imaging Physics, The University of Texas MD Anderson Cancer CenterDepartment of Breast Imaging, The University of Texas MD Anderson Cancer Center Department of Imaging Physics, The University of Texas MD Anderson Cancer CenterAbstract We developed a practical framework to construct digital twins for predicting and optimizing triple-negative breast cancer (TNBC) response to neoadjuvant chemotherapy (NAC). This study employed 105 TNBC patients from the ARTEMIS trial (NCT02276443, registered on 10/21/2014) who received Adriamycin/Cytoxan (A/C)-Taxol (T). Digital twins were established by calibrating a biology-based mathematical model to patient-specific MRI data, which accurately predicted pathological complete response (pCR) with an AUC of 0.82. We then used each patient’s twin to theoretically optimize outcome by identifying their optimal A/C-T schedule from 128 options. The patient-specifically optimized treatment yielded a significant improvement in pCR rate of 20.95–24.76%. Retrospective validation was conducted by virtually treating the twins with AC-T schedules from historical trials and obtaining identical observations on outcomes: bi-weekly A/C-T outperforms tri-weekly A/C-T, and weekly/bi-weekly T outperforms tri-weekly T. This proof-of-principle study demonstrates that our digital twin framework provides a practical methodology to identify patient-specific TNBC treatment schedules.https://doi.org/10.1038/s41746-025-01579-1
spellingShingle Chengyue Wu
Ernesto A. B. F. Lima
Casey E. Stowers
Zhan Xu
Clinton Yam
Jong Bum Son
Jingfei Ma
Gaiane M. Rauch
Thomas E. Yankeelov
MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens
npj Digital Medicine
title MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens
title_full MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens
title_fullStr MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens
title_full_unstemmed MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens
title_short MRI-based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens
title_sort mri based digital twins to improve treatment response of breast cancer by optimizing neoadjuvant chemotherapy regimens
url https://doi.org/10.1038/s41746-025-01579-1
work_keys_str_mv AT chengyuewu mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens
AT ernestoabflima mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens
AT caseyestowers mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens
AT zhanxu mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens
AT clintonyam mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens
AT jongbumson mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens
AT jingfeima mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens
AT gaianemrauch mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens
AT thomaseyankeelov mribaseddigitaltwinstoimprovetreatmentresponseofbreastcancerbyoptimizingneoadjuvantchemotherapyregimens