Multiparametric monitoring of chemotherapy treatment response in locally advanced breast cancer using quantitative ultrasound and diffuse optical spectroscopy
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William T. Tran1,4, Charmaine Childs4, Lee Chin1, Elzbieta Slodkowska6, Lakshmanan Sannachi1,3, Hadi Tadayyon1,3, Elyse Watkins1, Sharon Lemon Wong7, Belinda Curpen5, Ahmed El Kaffas1, Azza Al-Mahrouki1, Ali Sadeghi-Naini1, Gregory J. Czarnota2,3
1Department of Radiation Oncology, Sunnybrook Hospital, Toronto, Canada
2Department of Radiation Oncology, University of Toronto, Toronto, Canada
3Department of Medical Biophysics, University of Toronto, Toronto, Canada
4Centre for Health and Social Care Research, Sheffield Hallam University, Sheffield, UK
5Division of Radiology, Sunnybrook Hospital, Toronto, Canada
6Division of Anatomic Pathology, Sunnybrook Hospital, Toronto, Canada
7Department of Nursing, Sunnybrook Hospital, Toronto, Canada
Gregory J. Czarnota, e-mail: [email protected]
Keywords: diffuse optical spectroscopy, quantitative ultrasound, locally advanced breast cancer, treatment monitoring, neoadjuvant chemotherapy
Received: September 01, 2015 Accepted: February 05, 2016 Published: March 02, 2016
Purpose: This study evaluated pathological response to neoadjuvant chemotherapy using quantitative ultrasound (QUS) and diffuse optical spectroscopy imaging (DOSI) biomarkers in locally advanced breast cancer (LABC).
Materials and Methods: The institution’s ethics review board approved this study. Subjects (n = 22) gave written informed consent prior to participating. US and DOSI data were acquired, relative to the start of neoadjuvant chemotherapy, at weeks 0, 1, 4, 8 and preoperatively. QUS parameters including the mid-band fit (MBF), 0-MHz intercept (SI), and the spectral slope (SS) were determined from tumor ultrasound data using spectral analysis. In the same patients, DOSI was used to measure parameters relating to tumor hemoglobin and composition. Discriminant analysis and receiver-operating characteristic (ROC) analysis was used to classify clinical and pathological response during treatment and to estimate the area under the curve (AUC). Additionally, multivariate analysis was carried out for pairwise QUS/DOSI parameter combinations using a logistic regression model.
Results: Individual QUS and DOSI parameters, including the (SI), oxy-hemoglobin (HbO2), and total hemoglobin (HbT) were significant markers for response after one week of treatment (p < 0.01). Multivariate (pairwise) combinations increased the sensitivity, specificity and AUC at this time; the SI + HbO2 showed a sensitivity/specificity of 100%, and an AUC of 1.0.
Conclusions: QUS and DOSI demonstrated potential as coincident markers for treatment response and may potentially facilitate response-guided therapies. Multivariate QUS and DOSI parameters increased the sensitivity and specificity of classifying LABC patients as early as one week after treatment.
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