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. 2014 Dec 1;20(23):6006-15.
doi: 10.1158/1078-0432.CCR-14-1415. Epub 2014 Oct 7.

Predicting Breast Tumor Response to Neoadjuvant Chemotherapy With Diffuse Optical Spectroscopic Tomography Prior to Treatment

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Free PMC article

Predicting Breast Tumor Response to Neoadjuvant Chemotherapy With Diffuse Optical Spectroscopic Tomography Prior to Treatment

Shudong Jiang et al. Clin Cancer Res. .
Free PMC article

Abstract

Purpose: To determine whether pretreatment biomarkers obtained from diffuse optical spectroscopic tomographic (DOST) imaging predicts breast tumor response to neoadjuvant chemotherapy (NAC), which would have value to potentially eliminate delays in prescribing definitive local regional therapy that may occur from a standard complete 6- to 8-month course of NAC.

Experimental design: Nineteen patients undergoing NAC were imaged with DOST before, during, and after treatment. The DOST images of total hemoglobin concentration (HbT), tissue oxygen saturation (StO2), and water (H2O) fraction at different time points have been used for testing the abilities of differentiating patients having pathologic complete response (pCR) versus pathologic incomplete response (pIR).

Results: Significant differences (P < 0.001, AUC = 1.0) were found between pCR patients versus pIR in outcome, based on the percentage change in tumor HbT within the first cycle of treatment. In addition, pretreatment tumor HbT (pretreatment HbT) relative to the contralateral breast was statistically significant (P = 0.01, AUC = 0.92) in differentiating pCR from pIR.

Conclusions: This is the first clinical evidence that DOST HbT may differentiate the two groups with predictive significance based on data acquired before NAC even begins. The study also demonstrates the potential of accelerating the validation of optimal NAC regimens through future randomized clinical trials by reducing the number of patients required and the length of time they need to be followed by using a validated imaging surrogate as an outcome measure.

Figures

Figure 1
Figure 1
Images and graphs of a pCR case with (a) DOST images prior, during and after NAC. In (b), axial post contrast subtraction MRI before NAC shows an enhancing mass (yellow arrow) in the deep central left breast that measured 5.9 × 4.3 × 5.3 cm. In (c), (d) and (e), graphs of the tumor HbT, StO2 and H2O are shown at different time points.
Figure 1
Figure 1
Images and graphs of a pCR case with (a) DOST images prior, during and after NAC. In (b), axial post contrast subtraction MRI before NAC shows an enhancing mass (yellow arrow) in the deep central left breast that measured 5.9 × 4.3 × 5.3 cm. In (c), (d) and (e), graphs of the tumor HbT, StO2 and H2O are shown at different time points.
Figure 2
Figure 2
Images and graphs of a pIR case with (a) DOST images prior, during and after NAC. In (b), axial post contrast subtraction MRI before NAC shows the index invasive breast cancer (upper image) in the lateral right breast at 9:00 o’clock and measuring 5.4 × 3.4 × 5.2 cm, and a subpectoral lymph node metastasis (lower image) at 12:00 o’clock measuring 2.5 × 1.9 × 3.0 cm. The yellow arrows show the dominant tumors in each image. Additionally, rim enhancing skin metastases exist overlying the index tumor at 9:00 o’clock (arrowheads). In (c),(d) and (e), HbT, StO2 and H2O are graphed for different time points.
Figure 2
Figure 2
Images and graphs of a pIR case with (a) DOST images prior, during and after NAC. In (b), axial post contrast subtraction MRI before NAC shows the index invasive breast cancer (upper image) in the lateral right breast at 9:00 o’clock and measuring 5.4 × 3.4 × 5.2 cm, and a subpectoral lymph node metastasis (lower image) at 12:00 o’clock measuring 2.5 × 1.9 × 3.0 cm. The yellow arrows show the dominant tumors in each image. Additionally, rim enhancing skin metastases exist overlying the index tumor at 9:00 o’clock (arrowheads). In (c),(d) and (e), HbT, StO2 and H2O are graphed for different time points.
Figure 3
Figure 3
Box plots of (a) early % changes in tumor HbT between the Pre-Tx and the last imaging session in the first NAC cycle are shown with (b) Pre-TxHbT, (c) Pre-Tx contrast in StO2 and (d) Pre-Tx contrast in H2O.
Figure 4
Figure 4
AUC curves are shown for (a) early percentage changes of tumor HbT between the Pre-Tx and the last imaging session in the first NAC cycle, and (b) Pre-TxHbT, (c) Pre-Tx contrast in StO2, and (d) Pre-Tx contrast in H2O.

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