Monitoring neo-adjuvant chemotherapy: comparison of contrast-enhanced spectral mammography (CESM) and MRI versus breast cancer characteristics

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1 Monitoring neo-adjuvant chemotherapy: comparison of contrast-enhanced spectral mammography (CESM) and MRI versus breast cancer characteristics Poster No.: B-1062 Congress: ECR 2016 Type: Scientific Paper Authors: V. Iotti, S. Ravaioli, R. Sghedoni, C. Coriani, R. Vacondio, S Caffarri, A. Nitrosi, G. Tondelli, P. Pattacini ; Reggio Emilia/IT, 2 3 Guastalla/IT, Scandiano/IT Keywords: Breast, Oncology, Mammography, MR, Treatment effects, Chemotherapy, Cancer DOI: /ecr2016/B-1062 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 25

2 Purpose To compare Contrast-Enhanced Spectral Mammography (CESM) and ContrastEnhanced MRI (MRI) in assessing response to Neo-Adjuvant Chemotherapy (NAC) as a function of breast cancer histological and biological characteristics. Breast Cancer is the most common cancer in women worldwide Neo-Adjuvant Chemotherapy (NAC): treatment given before surgery to shrink tumor, for (according to AIOM Guidelines): # Locally Advanced Breast Cancer (largest diameter > 25 mm, involving breast skin and nodes) # Inflammatory Carcinoma # Operable carcinoma with indication of mastectomy, to allow more conservative surgery # HER2+ Carcinoma The ability to distinguish between responsive and non-responsive patients is of critical importance for making treatment choices. The accuracy of breast imaging techniques to assess clinical response depended on breast cancer subtypes. Lesion size changes and type of vascularization are used to evaluate NAC response for breast cancer: # Contrast-Enhanced Magnetic Resonance Imaging (MRI): the most sensitive method for assessing the response to NAC # Contrast-Enhanced Spectral Mammography (CESM): emerging diagnostic tools Methods and materials 54 consenting women (age range y/o; mean age 54 y/o) with breast cancer and indication of NAC were enrolled into this prospective study between October 2012 and December Page 2 of 25

3 #47 patients completed NAC and underwent surgery; #7 excluded because of premature NAC interruption. Inclusion criteria: Diagnosis of breast cancer at stage II or III with indication of NAC; Over 18 years old; Agreement to participate. Exclusion criteria: Known BRCA mutation; General MRI contraindications (e.g. PM); Contraindications to the administration of iodine or gadolinium contrast agent; Pregnancy. Histological and biological characteristics were as listed in Fig. 1 on page 3. Patients underwent CE-MRI and CESM before, after the first cycle and after the end of NAC. Response to therapy was evaluated using the variation of the largest dimension of malignancies measured on CE-MRI and CESM image sets, according to RECIST 1.1 criteria. CESM and CE-MRI size measurements were compared to post-operative histopathology through correlation (Pearson's "r") and agreement (Paired t-test p-value). Images for this section: Page 3 of 25

4 Fig. 1: Cancer Histological and Biological characteristics Page 4 of 25

5 Results We evaluated CESM and MRI separately according to the neoplastic: histological characteristics (Fig. 2 on page 5): Ductal Infiltrating Caricinoma (Fig. 3 on page 7, Fig. 4 on page 9, Fig. 5 on page 11), Lobular Infiltrating Carcinoma (Fig. 6 on page 13) and Metaplasic Carcinoma (Fig. 7 on page 15) biological characteristics (Fig. 8 on page 6): Luminal A (Fig. 9 on page 17), Luminal B (Fig. 10 on page 18, Fig. 11 on page 18), Luminal B HER2+ (Fig. 12 on page 19), Triple Negative (Fig. 13 on page 20) and HER2+ (Fig. 14 on page 21). Overall correlation coefficients for CE-MRI and CESM versus pathology at end of NAC were r=0.728 and r=0.866, with mean underestimations in size of 7.5mm (p=0.003) and 4.1mm (p=0.023), respectively. As reported in Fig. 15 on page 22, main variances in correlation were seen in ILC (r= for CE-MRI and r=0.628 for CESM) and Luminal B (r= for CE-MRI and r=0.750 for CESM). Main limitations in assessing tumor response according to the evaluation of dimension and vascularization: changes in tumor micro-vessel functionality after NAC the overall loss of cellularity is not always reflected by a decrease in tumor size, because the fibrous stroma remains when the residual cancer cells present as small foci or scattered cells spread throughout the tumor bed, receive nutrients via diffusion and not from vascular perfusion. Different contrast media (iodinated vs gadolinium-based), acquisition timing and resolving power, may partially support the different results observed with CESM and MRI. Images for this section: Page 5 of 25

6 Fig. 2: Histological Overview Page 6 of 25

7 Fig. 8: Biological Overview Page 7 of 25

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9 Fig. 3: 63-year-old woman with 35-mm Invasive DUCTAL G3 Carcinoma in left breast. Partial response to NAC, correctly diagnosed both with CESM and MRI. Page 9 of 25

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11 Fig. 4: 57-year-old woman with 43-mm Invasive DUCTAL G2 Carcinoma in right breast. Partial response to NAC, correctly diagnosed with CESM but misinterpreted as complete response according to MRI. Page 11 of 25

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13 Fig. 5: 48-year-old woman with 30-mm Invasive DUCTAL G2 Carcinoma in left breast. Partial response to NAC, misinterpreted as complete response both with CESM and MRI, maybe for the reduced vascularization linked to the therapy-related fall of Ki67 (from 38% before NAC to 2% after NAC). Page 13 of 25

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15 Fig. 6: 69-year-old woman with 43-mm Invasive LOBULAR Carcinoma in left breast. Partial response to NAC, misinterpreted as complete response both with CESM and MRI, maybe correlated to the presence of neoplastic thrombus obstructing the contrastenhancement via perfusion. Page 15 of 25

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17 Fig. 7: 45-year-old woman with 43-mm METAPLASTIC Carcinoma in right breast. Partial response to NAC, correctly diagnosed both with CESM and MRI. Fig. 9: 41-year-old woman with 80-mm IDC-G2 Luminal A in right breast. Stable disease after NAC, with a shrinkage of 20%. Page 17 of 25

18 Fig. 10: 62-year-old woman with 22-mm IDC-G3 Luminal B in right breast. Partial response to NAC, with a 4-mm residual lesion, correctly diagnosed both with CESM and MRI. Page 18 of 25

19 Fig. 11: 48-year-old woman with 97-mm ILC Luminal B in left breast. Partial response to NAC, correctly diagnosed with CESM but misinterpreted as complete response according to MRI. Page 19 of 25

20 Fig. 12: 47-year-old woman with 25-mm IDC-G2 Luminal B HER2+ in left breast. Partial response to NAC, correctly diagnosed both with CESM and MRI. Page 20 of 25

21 Fig. 13: 41-year-old woman with 27-mm IDC-G3 Triple Negative in left breast. Complete response to NAC, correctly diagnosed both with CESM and MRI. Page 21 of 25

22 Fig. 14: 46-year-old woman with 58-mm IDC-G3 HER2+ in left breast. Complete response to NAC, correctly diagnosed both with CESM and MRI. Page 22 of 25

23 Fig. 15: Correlation coefficients (r) calculated overall, and according to the different neoplastic histological and biological characteristics. Page 23 of 25

24 Conclusion #CESM and MRI lesion size measurements were highly correlated and in strong agreement. #CESM seems as reliable as MRI in assessing the response to NAC, with encouraging results. #CESM may be an alternative to MRI in the assessment of NAC response, in particular for challenging histological and biological types of breast carcinomas as ILC and Luminal B. Personal information References Dromain C et al. Contrast-enhanced digital mammography. Eur J Radiol Fallenberg EM et al. Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size. Eur Radiol Lobbes MB et al. The quality of tumor size assessment by contrastenhanced spectral mammography and the benefit of additional breast MRI. J Cancer Dromain C et al. Optimization of contrast-enhanced spectral mammography depending on clinical indication. J Med Imaging (Bellingham) Dromain C et al. Dual-energy contrast-enhanced digital mammography: initial clinical results. Eur Radiol Lobbes MB et al. The role of magnetic resonance imaging in assessing residual disease and pathologic complete response in breast cancer patients receiving neoadjuvant chemotherapy: a systematic review. Insights Imaging Page 24 of 25

25 7. Bufi E et al. Role of the Apparent Diffusion Coefficient in the Prediction of Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer. Clin Breast Cancer Michishita S et al. Prediction of pathological complete response to neoadjuvant chemotherapy by magnetic resonance imaging inbreast cancer patients. Breast Zhang Z et al. Evaluating the response of neoadjuvant chemotherapy for treatment of breast cancer: are tumor biomarkers and dynamic contrast enhanced MR images useful predictive tools? J Thorac Dis Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation, diagnostic accuracy, and transfer to clinical practice. Radiology Kuhl CK. Current status of breast MR imaging. Part 2. Clinical applications. Radiology Thompson AM. Neoadjuvant treatment of breast cancer. Ann Oncol Page 25 of 25