It has been proposed that magnetic resonance imaging (MRI) be used to guide breast cancer surgery by differentiating residual tumor from pathologic complete response (pCR) after neoadjuvant chemotherapy. This meta-analysis examines MRI accuracy in detecting residual tumor, investigates variables potentially affecting MRI performance, and compares MRI with other tests. A systematic literature search was undertaken. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate (relative) diagnostic odds ratios ([R]DORs). Summary sensitivity (correct identification of residual tumor), specificity (correct identification of pCR), and areas under the SROC curves (AUCs) were derived. All statistical tests were two-sided. Forty-four studies (2050 patients) were included. The overall AUC of MRI was 0.88. Accuracy was lower for “standard” pCR definitions (referent category) than “less clearly described” (RDOR = 2.41, 95% confidence interval [CI] = 1.11 to 5.23) or “near-pCR” definitions (RDOR = 2.60, 95% CI = 0.73 to 9.24; P = .03.) Corresponding AUCs were 0.83, 0.90, and 0.91. Specificity was higher when negative MRI was defined as contrast enhancement less than or equal to normal tissue (0.83, 95% CI = 0.64 to 0.93) vs no enhancement (0.54, 95% CI = 0.39 to 0.69; P = .02), with comparable sensitivity (0.83, 95% CI = 0.69 to 0.91; vs 0.87, 95% CI = 0.80 to 0.92; P = .45). MRI had higher accuracy than mammography (P = .02); there was only weak evidence that MRI had higher accuracy than clinical examination (P = .10). No difference in MRI and ultrasound accuracy was found (P = .15). MRI accurately detects residual tumor after neoadjuvant chemotherapy. Accuracy was lower when pCR was more rigorously defined, and specificity was lower when test negativity thresholds were more stringent; these definitions require standardization. MRI is more accurate than mammography; however, studies comparing MRI and ultrasound are required.
Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast
Magnetic resonance imaging (MRI) has been proposed to have a role in predicting final pathologic response when undertaken early during neoadjuvant chemotherapy (NAC) in breast cancer. This paper examines the evidence for MRI's accuracy in early response prediction. A systematic literature search (to February 2011) was performed to identify studies reporting the accuracy of MRI during NAC in predicting pathologic response, including searches of MEDLINE, PREMEDLINE, EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects, range 16-188). Dynamic contrast-enhanced (DCE) MRI was typically performed after 1-2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or bidimensional tumour size, three-dimensional volume, quantitative dynamic contrast measurements (volume transfer constant [Ktrans], exchange rate constant [k(ep)], early contrast uptake [ECU]), and descriptive patterns of tumour reduction. Thresholds for identifying response varied across studies. Definitions of response included pathologic complete response (pCR), near-pCR, and residual tumour with evidence of NAC effect (range of response 0-58%). Heterogeneity across MRI parameters and the outcome definition precluded statistical meta-analysis. Based on descriptive presentation of the data, sensitivity/specificity pairs for prediction of pathologic response were highest in studies measuring reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume (pCR or near-pCR), at high thresholds (typically >50%); lower sensitivity/specificity pairs were evident in studies measuring reductions in uni- or bidimensional tumour size. However, limitations in study methodology and data reporting preclude definitive conclusions. Methods proposed to address these limitations include: statistical comparison between MRI parameters, and MRI vs other tests (particularly ultrasound and clinical examination); standardising MRI thresholds and pCR definitions; and reporting changes in NAC based on test results. Further studies adopting these methods are warranted.
Magnetic resonance imaging (MRI) may guide breast cancer surgery by measuring residual tumor size post-neoadjuvant chemotherapy (NAC). Accurate measurement may avoid overly radical surgery or reduce the need for repeat surgery. This individual patient data (IPD) meta-analysis examines MRI’s agreement with pathology in measuring the longest tumor diameter and compares MRI with alternative tests. A systematic review of MEDLINE, EMBASE, PREMEDLINE, Database of Abstracts of Reviews of Effects, Heath Technology Assessment, and Cochrane databases identified eligible studies. Primary study authors supplied IPD in a template format constructed a priori. Mean differences (MDs) between tests and pathology (i.e. systematic bias) were calculated and pooled by the inverse variance method; limits of agreement (LOA) were estimated. Test measurements of 0.0 cm in the presence of pathologic residual tumor, and measurements >0.0 cm despite pathologic complete response (pCR) were described for MRI and alternative tests. Eight studies contributed IPD (N = 300). The pooled MD for MRI was 0.0 cm (LOA: +/−3.8 cm). Ultrasound underestimated pathologic size (MD: −0.3 cm) relative to MRI (MD: 0.1 cm), with comparable LOA. MDs were similar for MRI (0.1 cm) and mammography (0.0 cm), with wider LOA for mammography. Clinical examination underestimated size (MD: −0.8 cm) relative to MRI (MD: 0.0 cm), with wider LOA. Tumors “missed” by MRI typically measured 2.0 cm or less at pathology; tumors >2.0 cm were more commonly “missed” by clinical examination (9.3 %). MRI measurements >5.0 cm occurred in 5.3 % of patients with pCR, but were more frequent for mammography (46.2 %). There was no systematic bias in MRI tumor measurement, but LOA are large enough to be clinically important. MRI’s performance was generally superior to ultrasound, mammography, and clinical examination, and it may be considered the most appropriate test in this setting. Test combinations should be explored in future studies.