TY - JOUR
T1 - MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
AU - Wu, Chengyue
AU - Jarrett, Angela M.
AU - Zhou, Zijian
AU - Elshafeey, Nabil
AU - Adrada, Beatriz E.
AU - Candelaria, Rosalind P.
AU - Mohamed, Rania M.M.
AU - Boge, Medine
AU - Huo, Lei
AU - White, Jason B.
AU - Tripathy, Debu
AU - Valero, Vicente
AU - Litton, Jennifer K.
AU - Yam, Clinton
AU - Son, Jong Bum
AU - Ma, Jingfei
AU - Rauch, Gaiane M.
AU - Yankeelov, Thomas E.
N1 - Publisher Copyright:
©2022 American Association for Cancer Research.
PY - 2022/9/15
Y1 - 2022/9/15
N2 - 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 ¼ 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 ¼ 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.
AB - 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 ¼ 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 ¼ 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85138448047&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-22-1329
DO - 10.1158/0008-5472.CAN-22-1329
M3 - Article
C2 - 35914239
AN - SCOPUS:85138448047
SN - 0008-5472
VL - 82
SP - 3394
EP - 3404
JO - Cancer Research
JF - Cancer Research
IS - 18
ER -