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Ex Vivo MRI Evaluation of Breast Tumors: A Novel Tool for Verifying Resection of Nonpalpable Only MRI Detected Lesions
relationship between shear-wave elastographic findings and histologic prognostic factors. Radiology. 2012; 263:673-677.
study of 939 masses. Radiology. 2012;262:435-449. 2. Evans A, Whelehan P, Thomson K, et al. Differentiating benign from malignant solid breast masses: value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BIRADS classification. Br J Cancer. 2012;107:224-229. 3. Evans A, Whelehan P, Thomson K, et al. Invasive breast cancer:
Ex Vivo MRI Evaluation of Breast Tumors: A Novel Tool for Verifying Resection of Nonpalpable Only MRI Detected Lesions Agresti R, Trecate G, Ferraris C, et al (Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; et al) Breast J 19:659-663, 2013
A fundamental question in surgery of only magnetic resonance imaging (MRI)-detected breast lesions is to ensure their removal when they are not palpable by clinical examination and surgical exploration. This is especially relevant in the case of small tumors, carcinoma in situ or lobular carcinoma. Thirty-nine patients were enrolled in the study, 21 patients with breast lesions detected by both conventional imaging and breast MRI (bMRI) and 18 patients with bMRI findings only. Preoperative bMRI allowed staging the disease and localizing the lesion. In the operating theater, contrast medium was injected 1 minute before skin incision. After removal, surgical specimens were submitted to ex vivo MRI, performed using a dedicated surface coil and
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4. Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414-4422. 5. Hayashi M, Yamamoto Y, Ibusuki M, et al. Evaluation of tumor stiffness by elastography is predictive for
Spair inversion recovery sequences for suppression of fat signal intensity. All MRI enhancing lesions were completely included within the surgical specimen and visualized by ex vivo MRI. In the first 21 patients, bMRI was able to visualize branching margins or satellite nodules around the core lesion, and allowed for better staging of the surrounding in situ carcinoma; in the last 18 patients, eight of whom were breast cancer type 1 susceptibility protein (BRCA) mutation carriers, bMRI identified 12 malignant tumors, otherwise undetectable, that were all visualized by ex vivo MRI. This is the first description of a procedure that re-enhances breast lesions within a surgical specimen, demonstrating the surgical removal of nonpalpable breast lesions diagnosed only with bMRI. This new strategy reproduces the morphology and the entire extension of the primary lesion on the specimen, with potentially better local surgical control, reducing additional unplanned surgery. In this prospective study, Agresti and colleagues from Milan, Italy, aimed to assess the use of ex vivo MRI of nonpalpable breast lesions detected only on MRI, using intravenous
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 2 2014
pathologic complete response to neoadjuvant chemotherapy in patients with breast cancer. Ann Surg Oncol. 2012;19:3042-3049. 6. Falou O, Sadeghi-Naini A, Prematilake S, et al. Evaluation of neoadjuvant chemotherapy response in women with locally advanced breast cancer using ultrasound elastography. Transl Oncol. 2013;6: 17-24.
gadolinium injected 1 minute prior to surgical excision. The study used a preoperative protocol to localize suspicious lesions under MRI, including positioning a lipidic vitamin E tablet as an external marker and then marking the skin with a pen to identify the surgical site. The authors found that in 18 patients with suspicious lesions detected via MRI only, there were 12 malignant tumors, and all 12 were visualized by ex vivo MRI. In this study, ex vivo MRI accurately depicted the morphology and extent of the primary lesions. This approach has the potential to improve local surgical control and intraoperative margin assessment. One area of interest in which ex vivo MRI lesion verification may be highly beneficial is ductal carcinoma in situ (DCIS). In the past decade, MRI has been shown to have the highest sensitivity for the detection of DCIS (compared with mammography and ultrasonography). A study by Kuhl and colleagues1 demonstrated that the sensitivity of MRI for DCIS was 92%, compared with 56% for mammography. The MRI sensitivity was higher in highgrade DCIS than in intermediate- and low-grade DCIS. Ex vivo MRI
evaluation of surgical specimens may be able to provide an accurate depiction of the extent of disease in patients with DCIS. Specimen radiography is another method used to evaluate surgical specimens and to verify the removal of lesions detected via MRI only. In a study by Erguvan-Dogan and colleagues, sliced specimen radiography revealed an abnormality similar to that seen on dynamic contrastenhanced bMRI in 9 (82%) of 11 cases. Although mammographically occult, all 5 of the malignant lesions (3 invasive ductal carcinomas and 2 cases of DCIS) were correctly identified on specimen radiography, potentially owing to the overlapping breast parenchyma having been removed prior to specimen radiography.2 The technique described by Agresti and colleagues may be useful for lesions without associated marker clips that are difficult to access for
needle localization or biopsy, such as those near an implant or those close to the chest wall. Abe and colleagues3 compared postoperative specimen radiography to postoperative specimen MRI on a 9.4-Tesla MRI unit. They showed that susceptibility artifacts from marker placement had significant effects on image quality. In 3 of 9 invasive cancers, a part of the border of the invasive malignancy was not well seen because of clip artifacts. The study by Agresti and colleagues outlined the proper timing of intravenous gadolinium administration prior to surgical excision and noted that the optimal time to visualize the lesions ex vivo with MRI was 15 minutes after surgical removal. While this protocol may be helpful in verifying the removal of lesions detected only on MRI, this approach presents several logistical challenges, especially with regard to organizing resources and equipment and follow-
ing the proper MRI timing sequences for specimen evaluation.
Clinically Meaningful Tumor Reduction Rates Vary by Prechemotherapy MRI Phenotype and Tumor Subtype in the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657)
associated with clinically meaningful tumor reduction, and (3) whether MRI phenotype impacts concordance between pathologic and MRI size. Methods.dWe analyzed data from the I-SPY TRIAL, a multicenter, prospective NAC trial. Reduction in tumor size from >4 to #4 cm was considered clinically meaningful, as crossing this threshold was considered a reasonable cutoff for potential breast conservation therapy (BCT). MRI phenotypes were scored between one (well-defined) and five (diffuse) on pre-NAC MRIs. Results.dOf 174 patients with tumors >4 cm, 141 (81 %) had clinically meaningful tumor reduction. Response to therapy varied by MRI
phenotype (p ¼ 0.003), with welldefined phenotypes more likely than diffuse phenotypes to have clinically meaningful tumor shrinkage (91 vs. 72 %, p ¼ 0.037). Her2+ and triplenegative (Tneg) tumors had the highest rate of clinically meaningful tumor reduction (p ¼ 0.005). The concordance between tumor diameter on MRI and surgical pathology was highest for Her2+ and Tneg tumors, especially among tumors with solid imaging phenotypes (p ¼ 0.004). Discussion.dNAC allows most patients with large breast tumors to have clinically meaningful tumor reduction, meaning response that would impact ability to undergo BCT. However, response varies by imaging
Mukhtar RA, Yau C, Rosen M, et al (Univ of California, San Francisco; Univ of Pennsylvania, Philadelphia) Ann Surg Oncol 20:3823-3830, 2013
Purpose.dThis study was designed to determine (1) rates of clinically meaningful tumor reduction in breast tumor size following neoadjuvant chemotherapy (NAC), (2) which receptor subtypes and MRI phenotypes are
J. G. Schopp, MD G. J. Whitman, MD
References 1. Kuhl CK, Schrading S, Bieling HB, et al. MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet. 2007; 370:485-492. 2. Erguvan-Dogan B, Whitman GJ, Nguyen VA, et al. Specimen radiography in confirmation of MRIguided needle localization and surgical excision of breast lesions. AJR Am J Roentgenol. 2006;187: 339-344. 3. Abe H, Shimauchi A, Fan X, et al. Comparing post-operative human breast specimen radiograph and MRI in lesion margin and volume assessment. J Appl Clin Med Phys. 2012;13:3802.
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 2 2014
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study of 939 masses. Radiology. 2012;262:435-449. 2. Evans A, Whelehan P, Thomson K, et al. Differentiating benign from malignant solid breast masses: value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BIRADS classification. Br J Cancer. 2012;107:224-229. 3. Evans A, Whelehan P, Thomson K, et al. Invasive breast cancer:
Ex Vivo MRI Evaluation of Breast Tumors: A Novel Tool for Verifying Resection of Nonpalpable Only MRI Detected Lesions Agresti R, Trecate G, Ferraris C, et al (Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; et al) Breast J 19:659-663, 2013
A fundamental question in surgery of only magnetic resonance imaging (MRI)-detected breast lesions is to ensure their removal when they are not palpable by clinical examination and surgical exploration. This is especially relevant in the case of small tumors, carcinoma in situ or lobular carcinoma. Thirty-nine patients were enrolled in the study, 21 patients with breast lesions detected by both conventional imaging and breast MRI (bMRI) and 18 patients with bMRI findings only. Preoperative bMRI allowed staging the disease and localizing the lesion. In the operating theater, contrast medium was injected 1 minute before skin incision. After removal, surgical specimens were submitted to ex vivo MRI, performed using a dedicated surface coil and
134
4. Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414-4422. 5. Hayashi M, Yamamoto Y, Ibusuki M, et al. Evaluation of tumor stiffness by elastography is predictive for
Spair inversion recovery sequences for suppression of fat signal intensity. All MRI enhancing lesions were completely included within the surgical specimen and visualized by ex vivo MRI. In the first 21 patients, bMRI was able to visualize branching margins or satellite nodules around the core lesion, and allowed for better staging of the surrounding in situ carcinoma; in the last 18 patients, eight of whom were breast cancer type 1 susceptibility protein (BRCA) mutation carriers, bMRI identified 12 malignant tumors, otherwise undetectable, that were all visualized by ex vivo MRI. This is the first description of a procedure that re-enhances breast lesions within a surgical specimen, demonstrating the surgical removal of nonpalpable breast lesions diagnosed only with bMRI. This new strategy reproduces the morphology and the entire extension of the primary lesion on the specimen, with potentially better local surgical control, reducing additional unplanned surgery. In this prospective study, Agresti and colleagues from Milan, Italy, aimed to assess the use of ex vivo MRI of nonpalpable breast lesions detected only on MRI, using intravenous
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 2 2014
pathologic complete response to neoadjuvant chemotherapy in patients with breast cancer. Ann Surg Oncol. 2012;19:3042-3049. 6. Falou O, Sadeghi-Naini A, Prematilake S, et al. Evaluation of neoadjuvant chemotherapy response in women with locally advanced breast cancer using ultrasound elastography. Transl Oncol. 2013;6: 17-24.
gadolinium injected 1 minute prior to surgical excision. The study used a preoperative protocol to localize suspicious lesions under MRI, including positioning a lipidic vitamin E tablet as an external marker and then marking the skin with a pen to identify the surgical site. The authors found that in 18 patients with suspicious lesions detected via MRI only, there were 12 malignant tumors, and all 12 were visualized by ex vivo MRI. In this study, ex vivo MRI accurately depicted the morphology and extent of the primary lesions. This approach has the potential to improve local surgical control and intraoperative margin assessment. One area of interest in which ex vivo MRI lesion verification may be highly beneficial is ductal carcinoma in situ (DCIS). In the past decade, MRI has been shown to have the highest sensitivity for the detection of DCIS (compared with mammography and ultrasonography). A study by Kuhl and colleagues1 demonstrated that the sensitivity of MRI for DCIS was 92%, compared with 56% for mammography. The MRI sensitivity was higher in highgrade DCIS than in intermediate- and low-grade DCIS. Ex vivo MRI
evaluation of surgical specimens may be able to provide an accurate depiction of the extent of disease in patients with DCIS. Specimen radiography is another method used to evaluate surgical specimens and to verify the removal of lesions detected via MRI only. In a study by Erguvan-Dogan and colleagues, sliced specimen radiography revealed an abnormality similar to that seen on dynamic contrastenhanced bMRI in 9 (82%) of 11 cases. Although mammographically occult, all 5 of the malignant lesions (3 invasive ductal carcinomas and 2 cases of DCIS) were correctly identified on specimen radiography, potentially owing to the overlapping breast parenchyma having been removed prior to specimen radiography.2 The technique described by Agresti and colleagues may be useful for lesions without associated marker clips that are difficult to access for
needle localization or biopsy, such as those near an implant or those close to the chest wall. Abe and colleagues3 compared postoperative specimen radiography to postoperative specimen MRI on a 9.4-Tesla MRI unit. They showed that susceptibility artifacts from marker placement had significant effects on image quality. In 3 of 9 invasive cancers, a part of the border of the invasive malignancy was not well seen because of clip artifacts. The study by Agresti and colleagues outlined the proper timing of intravenous gadolinium administration prior to surgical excision and noted that the optimal time to visualize the lesions ex vivo with MRI was 15 minutes after surgical removal. While this protocol may be helpful in verifying the removal of lesions detected only on MRI, this approach presents several logistical challenges, especially with regard to organizing resources and equipment and follow-
ing the proper MRI timing sequences for specimen evaluation.
Clinically Meaningful Tumor Reduction Rates Vary by Prechemotherapy MRI Phenotype and Tumor Subtype in the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657)
associated with clinically meaningful tumor reduction, and (3) whether MRI phenotype impacts concordance between pathologic and MRI size. Methods.dWe analyzed data from the I-SPY TRIAL, a multicenter, prospective NAC trial. Reduction in tumor size from >4 to #4 cm was considered clinically meaningful, as crossing this threshold was considered a reasonable cutoff for potential breast conservation therapy (BCT). MRI phenotypes were scored between one (well-defined) and five (diffuse) on pre-NAC MRIs. Results.dOf 174 patients with tumors >4 cm, 141 (81 %) had clinically meaningful tumor reduction. Response to therapy varied by MRI
phenotype (p ¼ 0.003), with welldefined phenotypes more likely than diffuse phenotypes to have clinically meaningful tumor shrinkage (91 vs. 72 %, p ¼ 0.037). Her2+ and triplenegative (Tneg) tumors had the highest rate of clinically meaningful tumor reduction (p ¼ 0.005). The concordance between tumor diameter on MRI and surgical pathology was highest for Her2+ and Tneg tumors, especially among tumors with solid imaging phenotypes (p ¼ 0.004). Discussion.dNAC allows most patients with large breast tumors to have clinically meaningful tumor reduction, meaning response that would impact ability to undergo BCT. However, response varies by imaging
Mukhtar RA, Yau C, Rosen M, et al (Univ of California, San Francisco; Univ of Pennsylvania, Philadelphia) Ann Surg Oncol 20:3823-3830, 2013
Purpose.dThis study was designed to determine (1) rates of clinically meaningful tumor reduction in breast tumor size following neoadjuvant chemotherapy (NAC), (2) which receptor subtypes and MRI phenotypes are
J. G. Schopp, MD G. J. Whitman, MD
References 1. Kuhl CK, Schrading S, Bieling HB, et al. MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet. 2007; 370:485-492. 2. Erguvan-Dogan B, Whitman GJ, Nguyen VA, et al. Specimen radiography in confirmation of MRIguided needle localization and surgical excision of breast lesions. AJR Am J Roentgenol. 2006;187: 339-344. 3. Abe H, Shimauchi A, Fan X, et al. Comparing post-operative human breast specimen radiograph and MRI in lesion margin and volume assessment. J Appl Clin Med Phys. 2012;13:3802.
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 2 2014
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