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Monitoring Breast Cancer Response to Neoadjuvant Systemic Chemotherapy Using Parametric Contrast-Enhanced MRI A Pilot Study

Posted Apr 30, 2007 Updated Apr 7, 2023
By Chen-Pin Chou MD , Ming-Ting Wu MD , Hong-Tai Chang MD , Yu-Shin Lo MD , Huay-Ben Pan MD , Hadassa Degani PhD , Edna Furman-Haran PhD
14 min read

Rationale and Objectives

Neoadjuvant systemic therapy (NST) is the standard treatment for locally advanced breast cancer and a common option for primary operable disease. It is important to develop standardized imaging techniques that can monitor and quantify response to NST enabling treatment tailored to each individual patient, and facilitating surgical planning. Here we present a high spatial resolution, parametric method based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), which evaluates breast cancer response to NST.

Materials and Methods

DCE-MRI examinations were performed twice on 17 breast cancer patients, before and after treatment. Seven sets of axial breast images were sequentially recorded at 1.5 Tesla applying a three-dimensional, gradient echo at a spatial resolution ∼2 × 1.2 × 0.6 mm 3 and temporal resolution ∼2 minutes, using gadopentate dimeglumine (0.1 mmol/kg wt). Image analysis was based on a color-coded scheme related to physiologic perfusion parameters.

Results

A high Pearson correlation coefficient of 0.96 ( P < .0001) was found between the histopathologic estimation of viable neoplastic tissue volume and the segmented volume of all the pixels demonstrating fast and steady state washout after NST (colored in light red and green). Segmentation of these pixels before and after NST indicated response in terms of reduced tumor volume and a parallel decrease in enhancement rate which reflects diminished transcapillary transfer of the contrast agent.

Conclusions

The use of a parametric MRI technique provided a means to standardize segmentation and quantify changes in the perfusion of breast neoplastic tissue in response to NST. Whether this technique can serve to predict breast cancer recurrence and survival rates requires further clinical testing.

Neoadjuvant systemic therapy (NST) is the standard treatment for locally advanced breast cancer and a common option for primary operable disease. It is mainly designed to reduce tumor size, thereby improving surgical outcomes; to evaluate response to systemic therapy; and to obtain long-term, disease-free survival ( ). To achieve these goals, it is necessary to develop standardized imaging techniques that can noninvasively monitor the response of breast tumors to NST and quantify changes in their size and spread, as well as track specific biologic and physiologic markers of malignancy. Such imaging techniques could be useful in the early stages of treatment, to help predict response to chemotherapy, to enable treatment tailored to each individual patient, and to facilitate surgical planning at later treatment stages.

Magnetic resonance imaging (MRI), an important adjuvant tool for the detection and characterization of breast cancer ( ) has also been used to monitor the effects of NST ( ). Specifically, contrast-enhanced MRI provides a means to delineate the architectural and dynamic features of breast tumors and determine their size ( ). In recent years, several groups have examined whether contrast-enhanced MRI is accurate enough to evaluate residual tumor size after NST, and compared their results with final histopathologic assessment of mastectomy specimens ( ) and with data from other imaging methods such as mammography and sonography.

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Materials and methods

Patients, Treatment, and Timing of MRI

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Histologic Evaluation

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MRI

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Image Analysis

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Figure 1, Color-coded calibration map of the “three time point” (3TP) parametric images. (a) A color-coding scheme of the various enhancement patterns using selected imaging sets at three time points. The washout pattern is coded by color hue: red signifies a decline in signal intensity from the first to the second postcontrast time points; green, no change in signal intensity in the first and second postcontrast time points, within an average noise level; and blue, an increase in signal intensity from the first to the second postcontrast time points. The washin rate is denoted by color intensity (in arbitrary units ranging from 0 to 256) and normalized to the maximum intensity in the calibration map. (b) A calibration map calculated using the experimental conditions of this study. (c) Simulated enhancement curves of the white dots in (b) for ( k trans , v e ) = (0.9, 0.6) in red and ( k trans , v e ) = (0.2, 0.4) in blue. The broken black lines in (c) demonstrate the deviation of the estimated initial rates determined by the 3TP software, from the initial rates simulated on the basis of the Tofts model ( 31 ).

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Statistical Evaluation

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Results

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Table 1

Data from Mastectomy Specimens, Lymph Node Status, and Follow up

Case No. Stage NST No. Cycle Final Morphologic Distribution Residual Pathologic Volume † (cm 3 ) % Viable Neoplastic Cells † % Fibrosis † % Necrosis † Response Lymph Node Involved Recurrence-free Survival, Months 1 III 3 Localized NA NA NA NA PR 0 45 2 III 3 Localized 1.2 4 95 1 PR 5 22 ‡ 3 II 4 Localized 4.6 59 25 16 PR 0 33 4 III 3 Diffused 5.5 22 75 3 PR 0 44 5 III 3 Localized 43.3 15 80 5 PR 6 39 6 III 3 Localized 5.3 47 50 3 PR 0 50 7 III 3 Localized 27.9 70 25 5 PR 3 9 ‡ 8 II 3 Localized 6.5 62 34 4 SD 0 50 9 II 2 Diffused 2.8 47 50 3 SD 0 54 10 III 3 Diffused 14.7 76 20 4 SD 5 38 11 II 3 Localized 2.5 25 62 13 SD 0 44 12 III 4 Diffused 47.6 62 33 5 SD 22 6 ‡ 13 III 2 Localized 4.4 78 20 2 SD 0 44 14 ⁎ II 2 Diffused 46.1 5 75 20 SD 0 38 15 III 3 Diffused 60.9 47 20 33 SD 0 12 ‡ 16 III 3 Diffused 3.2 94 5 1 SD 2 53 17 II 3 Diffused 155 10 50 40 SD 1 48

NST: neoadjuvant systemic therapy; NA: not available; PR: partial response; SD: stable disease (defined using Response Evaluation Criteria in Solid Tumors).

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Figure 2, Subtracted and “three time point” (3TP) parametric images of localized infiltrating ductal carcinoma before and after neoadjuvant systemic therapy (NST) (Patient 8). (a) Subtracted (2 minutes postcontrast – zero time point) and 3TP parametric images of three central tumor slices before NST. (b) Frequency histograms of the intensities of red + green pixels (upper drawing) and blue pixels (lower drawing) analyzed from 3TP parametric images of the entire breast prior to NST. (c) Subtracted (2 minutes postcontrast minus zero time point) and parametric images of three central tumor slices after NST. (d) Frequency histograms of the intensity of red + green pixels (upper drawing) and blue pixels (lower drawing) analyzed from 3TP parametric images of the entire breast after NST. Note:—Because of the applied threshold of 30% enhancement in the first postcontrast scan, and the scaling of the color intensity based on the calibration map, the color intensity range started from 104. * Indicates the position of the median value.

Figure 3, Subtracted and “three time point” (3TP) parametric images of diffused infiltrating ductal carcinoma before and after neoadjuvant systemic therapy (NST) (Patient 12). (a) Subtracted (2 minutes post contrast – zero time point) and 3TP parametric images of three central tumor slices before NST. (b) Frequency histograms of the intensities of red + green pixels (upper drawing) and blue pixels (lower drawing) analyzed from images of the entire breast before NST. (c) Subtracted (2 minutes postcontrast – zero time point) and 3TP parametric images of three central tumor slices after NST. (d) Frequency histograms of the intensities of red + green pixels (upper drawing) and blue pixels (lower drawings) analyzed from images of the entire breast after NST. Note:—Because of the applied threshold of 30% enhancement in the first postcontrast scan, and the scaling of the color intensity based on the calibration map, the color intensity range started from 104. * Indicates the position of the median value.

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Table 2

Evaluation of the Segmentation and Intensity of the Regions Colored Red and Green in the Parametric Images Obtained Pre- and Post-NST

Case No. Volume of Red + Green Pixels, cm 3 Median Color Intensity of Red + Green Pixels Pretreatment Posttreatment Change (%) Pretreatment Posttreatment Change (%) 1 17.8 0.1 −99 140 116 −17 2 2.5 0.2 −92 160 120 −25 3 39.9 4.0 −90 213 122 −43 4 8.1 1.0 −87 186 125 −33 5 23.5 4.9 −79 110 125 +14 6 14.6 3.9 −73 210 255 +21 7 34.0 11.6 −66 235 170 −28 8 12.3 4.9 −60 239 138 −42 9 2.6 1.1 −59 194 135 −30 10 24.6 11.8 −52 216 210 −3 11 8.9 4.7 −47 126 120 −5 12 41.1 28.8 −30 192 149 −22 13 1.7 1.7 0 207 219 +6 14 3.3 3.5 +4 152 134 −12 15 20.2 31.7 +57 177 213 +20 16 2.7 4.4 +62 158 158 0 17 NA 17.9 NA NA 211 NA

NST: neoadjuvant systemic therapy; NA: not available.

Figure 4, Correlation of magnetic resonance imaging (MRI) and histopathologic analyses of viable tumor volume. (a) Pearson correlation and (b) Bland-Altman plot of the residual viable neoplastic volume determined by histologic grid morphometric analysis, as compared with the volume of the red + green pixels, determined by segmenting the “three time point” (3TP) parametric images from each patient. The graph displays a scatter diagram of the differences between the MRI and pathology derived tumor volumes plotted against the averages of these two measurements. Horizontal lines are drawn at the mean difference, and at the mean difference plus and minus the standard deviation of the differences. The error in estimating tumor volume from the 3TP – parametric images was estimated to be less than 10% of that volume and resulted from the nonautomated region of interest delineation of the whole breast which included enhanced regions outside the lesion (ie, blood vessels or normal breast parenchyma).

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Figure 5, “Three time point” parametric image of a central axial breast slice from a patient whose tumor responded to therapy (Patient 6). (a) Before neoadjuvant systemic therapy (NST). (b) After NST. Note the change in coloring (from red + green, to blue) and the presence of residual small cancerous loci (red) after NST.

Figure 6, “Three time point” parametric image of a central axial breast slice from a patient whose tumor failed to respond to therapy (Patient 15). (a) Before neoadjuvant systemic therapy (NST). (b) After NST. Note the substantial increase in tumor size and in area colored red after NST.

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Table 3

Evaluation of the Segmentation and Intensity of the Regions Colored Blue in the Parametric Images Obtained Pre- and Post-NST

Case No. Volume of Blue Pixels, cm 3 Median Color Intensity of Blue Pixels Pretreatment Posttreatment Change (%) Pretreatment Posttreatment Change (%) 1 6.4 0.3 −96 134 120 −10 2 1.6 0.3 −81 150 120 −20 3 16.0 2.4 −85 146 123 −16 4 5.1 0.9 −83 159 126 −21 5 5.9 2.8 −52 102 127 +25 6 4.0 5.0 +26 170 178 +5 7 13.4 4.2 −69 147 141 −4 8 5.2 2.2 −57 135 135 0 9 1.9 1.2 −38 155 136 −12 10 11.7 3.4 −71 154 140 −9 11 5.6 9.7 +75 134 129 −4 12 19.2 20.6 +7 147 141 −4 13 1.1 0.4 −64 162 158 −2 14 4.4 3.4 −23 141 131 −7 15 14.9 16.0 +7 159 159 0 16 2.2 1.3 −42 133 147 +11 17 NA 10.5 NA NA 158 NA

NST: neoadjuvant systemic therapy; NA: not available.

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Discussion

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Acknowledgments

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Academic Radiology, Volume 14, Issue 5
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