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Prediction of Clinicopathologic Response of Breast Cancer to Primary Chemotherapy at Contrast-enhanced MR Imaging: Initial Clinical Results¹

¹ From the Cancer Research UK Clinical Magnetic Resonance Research Group (A.R.P., C.H., J.S., M.O.L., J.E.H.) and the Breast Unit (L.A., T.P., A.M.), Institute of Cancer Research and the Royal Marsden NHS Trust, Surrey, England. Received September 2, 2002; revision requested November 4; final revision received May 19, 2005; accepted May 27; final version accepted July 18. Supported by Cancer Research Campaign grant SP1780-0103. Address correspondence to A.R.P., Paul Strickland Scanner Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK (e-mail: anwar.padhani{at}paulstrickland-scannercentre.org.uk).

View larger version (14K): [in a new window]   Figure 1a: Box plots show changes in (a) size and (b) transfer constant range values during chemotherapy correlated with pathologic response. White and gray boxes show change after one and two cycles of chemotherapy, respectively. All values are normalized to baseline. The boundaries of the box show 25th and 75th percentiles, and a line within the box marks the median value. Whiskers show 90th and 10th percentiles. Outliers () are also shown. Subgroup A1 = gross residual disease at pathologic evaluation with clinical progression or stable disease, subgroup A2 = gross residual disease at pathologic evaluation with clinical partial or complete response or minimal residual disease, group B = pathologic microscopic disease or complete response.

View larger version (17K): [in a new window]   Figure 1b: Box plots show changes in (a) size and (b) transfer constant range values during chemotherapy correlated with pathologic response. White and gray boxes show change after one and two cycles of chemotherapy, respectively. All values are normalized to baseline. The boundaries of the box show 25th and 75th percentiles, and a line within the box marks the median value. Whiskers show 90th and 10th percentiles. Outliers () are also shown. Subgroup A1 = gross residual disease at pathologic evaluation with clinical progression or stable disease, subgroup A2 = gross residual disease at pathologic evaluation with clinical partial or complete response or minimal residual disease, group B = pathologic microscopic disease or complete response.

View larger version (77K): [in a new window]   Figure 2: Images show transfer constant changes in 48-year-old postmenopausal woman with grade 2 infiltrating ductal-lobular carcinoma of the right breast responding to mitoxantrone and methotrexate chemotherapy. Columns show anatomic subtraction images (obtained by subtracting MR image acquired at 100 seconds after contrast agent administration from baseline image), corresponding transfer constant maps (color map displays range of 0–1 min–1), and histograms from pixel data. Rows show data before treatment and after one and two cycles of mitoxantrone and methotrexate chemotherapy, respectively. After one cycle of treatment (middle row), a decrease in the transfer constant median and range is seen (47% and 45%, respectively), compared with a 28% decrease in tumor size. After two treatments (bottom row), further decrease in transfer constant median and range is seen (80% and 75%, respectively) on the transfer constant histogram, compared with a 49% decrease in tumor size.

View larger version (69K): [in a new window]   Figure 3: Images show changes in transfer constant in 44-year-old perimenopausal woman with a grade 3 infiltrating ductal carcinoma of the left breast not responding to mitoxantrone and methotrexate chemotherapy. Columns show anatomic subtraction images (obtained by subtracting MR image acquired at 100 seconds after contrast agent administration from baseline image), corresponding transfer constant maps (color map displays range of 0–1 min–1), and histograms from pixel data. Rows show data before treatment and after one and two cycles of mitoxantrone and methotrexate chemotherapy, respectively. After one cycle of treatment (middle row), an increase in the transfer constant median and range is seen (57% and 34%, respectively), compared with a 10% decrease in tumor size. After two treatments (bottom row), a further increase in the transfer constant median and range is seen (186% and 181%, respectively) on the transfer constant histogram, compared with a 11% increase in tumor size.

View larger version (22K): [in a new window]   Figure 4: Scatter plot of correlation of pretreatment transfer constant values with transfer constant change after one cycle of treatment. Scatter plot and linear regression analysis demonstrate that changes in transfer constant values after one treatment are significantly related to transfer constant before treatment begins (r2 = 0.55, P = .001).

View larger version (21K): [in a new window]   Figure 5a: ROC analysis for predicting patients who would not benefit from neoadjuvant chemotherapy. (a) For size change analysis, after one cycle of treatment (area, 0.90), an increase, no change, or a decrease in size of less than 15% results in 100% sensitivity for identifying subgroup A1 patients (specificity, 85%). After two cycles of treatment (area, 0.93), this cutoff value had similar accuracy (sensitivity, 100%; specificity, 90%). (b) For transfer constant range analysis, after one cycle of treatment (area, 0.76), an increase, no change, or a decrease of less than 11% results in a 80% sensitivity for identifying subgroup A1 patients (specificity, 70%). After two cycles of treatment (area, 0.94), this cutoff value had 100% sensitivity and 75% specificity.

View larger version (21K): [in a new window]   Figure 5b: ROC analysis for predicting patients who would not benefit from neoadjuvant chemotherapy. (a) For size change analysis, after one cycle of treatment (area, 0.90), an increase, no change, or a decrease in size of less than 15% results in 100% sensitivity for identifying subgroup A1 patients (specificity, 85%). After two cycles of treatment (area, 0.93), this cutoff value had similar accuracy (sensitivity, 100%; specificity, 90%). (b) For transfer constant range analysis, after one cycle of treatment (area, 0.76), an increase, no change, or a decrease of less than 11% results in a 80% sensitivity for identifying subgroup A1 patients (specificity, 70%). After two cycles of treatment (area, 0.94), this cutoff value had 100% sensitivity and 75% specificity.