Contrast Enhanced Spectral Mammography (CESM) in Cancer Staging

Contrast Enhanced Spectral Mammography (CESM) in Cancer Staging Carrie Rochman,MD Assistant Professor,Breast Imaging UVA Dept of Radiology and Medical Imaging

Disclosures Research Agreement and Funding; Theraclion, Inc.

Objectives Imaging technique for CESM Appearance of breast cancer on CESM Role of CESM in cancer staging Primary detection Ipsilateral Extent of disease Detection of contralateral disease Role of CESM in cancer follow up Limitations of CESM

What is CESM? IV injection of low osmolar agents similar to those used for CT Dual energy mammogram performed after administration of IV iodinated contrast Two exposures at low and high energy Result = 2 mammographic images in each view Total imaging time 6-10 minutes

What is CESM? Low Energy (LE) image Similar to standard FFDM Provides morphologic information Recombined image Provides physiologic information about areas of increased blood flow

Normal CESM

Appearance of Breast Cancer on CESM - Mass L CC L CC L MLO L MLO Path = IDC

Cancer on CESM Non Mass Enhancement Path = DCIS

CESM vs. Digital Mammography Several studies comparing CESM to standard FFDM Improved sensitivity and specificity of CESM in the detection of breast cancer, especially in pre-menopausal women and women with dense breasts.

Objectives Imaging technique for CESM Appearance of breast cancer on CESM Role of CESM in cancer staging Primary detection Screening Recalls and Symptomatic Patients Ipsilateral Extent of disease Detection of contralateral disease Role of CESM in cancer follow up Limitations of CESM

CESM for Screening Recalls CESM (Black bar) improved sensitivity, specificity, PPV, and NPV when compared to FFDM (grey bar) CESM was especially useful in downgrading mammographic lesions based on false-positive recalls, as well as decreasing the need for 6-12 month follow up imaging for inconclusive findings (i.e., BI-RADS 3 findings) Lobbes, M. B. I., Lalji, U., Houwers, J., Nijssen, E. C., Nelemans, P. J., van Roozendaal, L., et al. (2014). Contrastenhanced spectral mammography in patients referred from the breast cancer screening programme. European Radiology, 24(7), 1668-1676.

CESM for Screening Recalls CESM increased diagnostic accuracy with improved sensitivity 96.9 % (+3.9 %), specificity 69.7 % (+33.8 %) and area under the ROC curve 0.833 (+0.188). Lalji, U. C., Houben, I. P. L., Prevos, R., Gommers, S., van Goethem, M., Vanwetswinkel, S., et al. (2016). Contrastenhanced spectral mammography in recalls from the dutch breast cancer screening program: Validation of results in a large multireader, multicase study. European Radiology, 26(12), 4371-4379.

70 y.o. Baseline Exam

Initial Imaging for Screening Recall CESM

CESM vs. FFDM for Symptomatic Patients Retrospective reader studies comparing CESM over standard mammography in symptomatic patients with suspicious palpable abnormalities ROC analysis performance of CESM over FFDM, with area under the curve of 0.93 versus 0.83 (p<0.025). Increased Sensitivity (95% versus 84%, p<0.025) Increased Specificity (81% versus 63%, p<0.025) Tumour size estimation at CESM was significantly more accurate than FFDM alone, the latter tending to undersize lesions. S.L. Tennant, J.J. James, E.J. Cornford, et al.contrast-enhanced spectral mammography improves diagnostic accuracy in the symptomatic setting Clin Radiol, 71 (11) (2016), pp. 1148-1155

Tumor Size: Comparison of CESM to FFDM and US Comparison of mean tumor size estimation on CESM, FFDM, and US vs. pathology gold standard Improved assessment of tumor size compared to FFDM and US C. Dromain, F. Thibault, S. Muller, et al.dual-energy contrast-enhanced digital mammography: initial clinical results Eur Radiol, 21 (2011), pp. 565-574 K.S. Blum, C. Rubbert, B. Mathys, et al.use of contrast-enhanced spectral mammography for intramammary cancer staging: preliminary results Acad Radiol, 21 (2014), pp. 1363-1369

Tumor size: Comparison of CESM to MRI Prospective study 80 cases (61 IDC, 13 ILC, 6 pure DCIS) Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. EM Fallenberg, C Dromain, F Diekmann, et al.contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size Eur Radiol, 24 (2014), pp. 256-264

Tumor Size: Ill Defined Palpable Breast Mass Pt is on Dialysis: Unable to Have MRI

Tumor Size

Multifocal Breast Cancer R CC Low Energy Image R CC Recombined Image R MLO Low Energy Image R MLO Recombined Image

Surgical Planning L CC FFDM Image 72 y/o female with a screening detected 19 mm high density, irregular mass with indistinct margins Biopsy at an outside facility demonstrated invasive ductal carcinoma.

Case Extent 3 ( of Disease: Surgical Planning L CC Low Energy Image L CC Recombined Image CESM was peformed to better assess tumor size. Biopsy was subsequently performed, demonstrating multifocal IDC. CESM was able to better determine extent of disease and directed the location for staging biopsy. The patient was able to undergo breast conserving therapy.

Detection of Contralateral Disease Synchronous breast cancer occurs in 1-3% of newly diagnosed breast cancers Lobular cancer in the index breast, family history of breast cancer, young age at diagnosis of first cancer and BRCA mutations are important risk factors that are known to be at increased risk for BBC Padmanabhan N, Subramanyan A, Radhakrishna S. Synchronous Bilateral Breast Cancers. J Clin Diagn Res. 2015;9(9):XC05-XC08. McCaul KA. Bilateral breast cancer incidence and survival. [PhD thesis]. North Terrace, ADELAIDE SA 5005: University of Adelaide; 2006. Available from: University of Adelaide, School of Population Health and Clinical Practice, Library E-Reserve

Contralateral Malignancy R CC Low Energy Image R CC Recombined Image R MLO Low Energy Image R MLO Recombined Image

Prior Normal Left Mammogram with DBT Pathology showed ILC

Role of CESM in Cancer Follow Up Response to Neoadjuvant Therapy Morphology of tumor with LE image Physiology of contrast enhancement CESM and MRI lesion size were highly correlated CESM at least as reliable as MRI in assessing the response to NAC Iotti V1, et al. Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging. Breast Cancer Res. 2017 Sep 11;19(1):106. doi: 10.1186/s13058-017-0899-1.

Monitoring Response to Neoadjuvant Therapy R MLO Recombined CESM R MLO Low Energy CESM R MLO Recombined CESM R MLO Low Energy CESM Prior Current

Follow Up after BCT Dense or heterogeneously dense High risk patients when MRI is no longer covered by insurance Previous malignancy mammographically occult R CC CESM R CC

Limitations of CESM Contraindications for CESM No biopsy ability Allergy to intravenous iodinated contrast Acute kidney injury (increase in serum Cr by >0.3 mg/dl within 48 hours or increase of >1.5 times baseline within prior 7 days) Chronic renal failure (GFR <30), unless patient is on regular hemodialysis Breast Implants False Positives False Negatives

Limitations of CESM False Positives Benign Lesions Fibroadenomas are the most common benign lesion that demonstrate enhancement on CESM Papillomas, hamartomas, intra-mammary lymph nodes, fat necrosis, and complicated cysts can also enhance

Bilateral Breast Cancer with Incidental False Positive Fibroadenoma R MLO L MLO R MLO L MLO

False Positive Papilloma

False Negatvie CESM Screening detected calcs. On CESM no enhancement is seen in the area of the calcifications. Path = intermediate grade DCIS. The absence of enhancement does not deter biopsy of suspicious imaging findings seen on the low energy CESM images.

R CC Recombined Image R MLO Recombined Image False Negative CESM Path = Well-differentiated IDC with lobular features. R CC Low Energy Image R MLO Low Energy Image

CESM False Negative Likely due to masking effect of marked background enhancement

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