TY - JOUR
T1 - Early Assessment Window for Predicting Breast Cancer Neoadjuvant Therapy using Biomarkers, Ultrasound, and Diffuse Optical Tomography
AU - Zhu, Quing
AU - Ademuyiwa, Foluso O.
AU - Young, Catherine
AU - Appleton, Catherine
AU - Covington, Matthew F.
AU - Ma, Cynthia
AU - Sanati, Souzan
AU - Hagemann, Ian S.
AU - Mostafa, Atahar
AU - Uddin, K. M.Shihab
AU - Grigsby, Isabella
AU - Frith, Ashley E.
AU - Hernandez-Aya, Leonel F.
AU - Poplack, Steven S.
N1 - Funding Information:
The authors appreciate the help of Clinical Trial Office of the Oncology Department of Washington University School of Medicine for patient consenting and scheduling. Drs. Catherine Young, Catherine Appleton, Matthew F. Covington, were faculty members of Radiology Department of Washington University in St Louis from the beginning of the study to July 2019. Dr. Steven Poplack was a faculty member of Radiology Department of Washington University in St Louis from the beginning of the study to June 2020.
Funding Information:
This study was funded by National Institutes of Health (R01EB002136, R01 CA228047). SPP acknowledges funding support from the Foundation for Barnes Jewish Hospital Ronald and Hanna Evens Endowed Chair in Women’s Health.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/8
Y1 - 2021/8
N2 - Purpose: The purpose of the study was to assess the utility of tumor biomarkers, ultrasound (US) and US-guided diffuse optical tomography (DOT) in early prediction of breast cancer response to neoadjuvant therapy (NAT). Methods: This prospective HIPAA compliant study was approved by the institutional review board. Forty one patients were imaged with US and US-guided DOT prior to NAT, at completion of the first three treatment cycles, and prior to definitive surgery from February 2017 to January 2020. Miller-Payne grading was used to assess pathologic response. Receiver operating characteristic curves (ROCs) were derived from logistic regression using independent variables, including: tumor biomarkers, US maximum diameter, percentage reduction of the diameter (%US), pretreatment maximum total hemoglobin concentration (HbT) and percentage reduction in HbT (%HbT) at different treatment time points. Resulting ROCs were compared using area under the curve (AUC). Statistical significance was tested using two-sided two-sample student t-test with P < 0.05 considered statistically significant. Logistic regression was used for ROC analysis. Results: Thirty-eight patients (mean age = 47, range 24–71 years) successfully completed the study, including 15 HER2 + of which 11 were ER + ; 12 ER + or PR + /HER2−, and 11 triple negative. The combination of HER2 and ER biomarkers, %HbT at the end of cycle 1 (EOC1) and %US (EOC1) provided the best early prediction, AUC = 0.941 (95% CI 0.869–1.0). Similarly an AUC of 0.910 (95% CI 0.810–1.0) with %US (EOC1) and %HbT (EOC1) can be achieved independent of HER2 and ER status. The most accurate prediction, AUC = 0.974 (95% CI 0.933–1.0), was achieved with %US at EOC1 and %HbT (EOC3) independent of biomarker status. Conclusion: The combined use of tumor HER2 and ER status, US, and US-guided DOT may provide accurate prediction of NAT response as early as the completion of the first treatment cycle. Clinical Trial Registration number: NCT02891681. https://clinicaltrials.gov/ct2/show/NCT02891681,Registration
AB - Purpose: The purpose of the study was to assess the utility of tumor biomarkers, ultrasound (US) and US-guided diffuse optical tomography (DOT) in early prediction of breast cancer response to neoadjuvant therapy (NAT). Methods: This prospective HIPAA compliant study was approved by the institutional review board. Forty one patients were imaged with US and US-guided DOT prior to NAT, at completion of the first three treatment cycles, and prior to definitive surgery from February 2017 to January 2020. Miller-Payne grading was used to assess pathologic response. Receiver operating characteristic curves (ROCs) were derived from logistic regression using independent variables, including: tumor biomarkers, US maximum diameter, percentage reduction of the diameter (%US), pretreatment maximum total hemoglobin concentration (HbT) and percentage reduction in HbT (%HbT) at different treatment time points. Resulting ROCs were compared using area under the curve (AUC). Statistical significance was tested using two-sided two-sample student t-test with P < 0.05 considered statistically significant. Logistic regression was used for ROC analysis. Results: Thirty-eight patients (mean age = 47, range 24–71 years) successfully completed the study, including 15 HER2 + of which 11 were ER + ; 12 ER + or PR + /HER2−, and 11 triple negative. The combination of HER2 and ER biomarkers, %HbT at the end of cycle 1 (EOC1) and %US (EOC1) provided the best early prediction, AUC = 0.941 (95% CI 0.869–1.0). Similarly an AUC of 0.910 (95% CI 0.810–1.0) with %US (EOC1) and %HbT (EOC1) can be achieved independent of HER2 and ER status. The most accurate prediction, AUC = 0.974 (95% CI 0.933–1.0), was achieved with %US at EOC1 and %HbT (EOC3) independent of biomarker status. Conclusion: The combined use of tumor HER2 and ER status, US, and US-guided DOT may provide accurate prediction of NAT response as early as the completion of the first treatment cycle. Clinical Trial Registration number: NCT02891681. https://clinicaltrials.gov/ct2/show/NCT02891681,Registration
KW - Near Infrared imaging
KW - Personalized medicine
KW - Predicting neoadjuvant therapy
KW - Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=85105508435&partnerID=8YFLogxK
U2 - 10.1007/s10549-021-06239-y
DO - 10.1007/s10549-021-06239-y
M3 - Article
C2 - 33970392
AN - SCOPUS:85105508435
SN - 0167-6806
VL - 188
SP - 615
EP - 630
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -