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IMAGING TO ASSESS
RESPONSE TO
NEOADJUVANT THERAPY
Lisa A. Mullen, MD
Assistant Professor
Breast Imaging Division
The Russell H. Morgan Department of
Radiology and Radiological Science Johns Hopkins Medicine
DISCLOSURES
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• Research support from IBM
OBJECTIVES
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• Review options for imaging at diagnosis
• Review options for imaging after NAC
• Review ACR Appropriateness Criteria
• Discuss performance of imaging options
• Discuss future directions
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INITIAL EVALUATION
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• Clinical examination
• Mammography, including DBT
• Breast Ultrasound
• MRI
• PET/CT
• MBI
ACR Appropriateness Criteria Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer
Expert Panel on Bteast Imaging:, Priscilla J. Slanetz. MD, MPH@ B .Unda Mov, MD, Paul Baron, MD, Roberta
M. dtFiorio, MD, MS, Edward 0. Green, MO, Samantha L. Heller, MD, PhD, Anna I. Holbrook, MD,Su..Ju Lee, MO.Alana A. Lewin, MD, Ana P. Lourenco. MD. Bethany Niell, MD, PhD. Ashley R. Stuckey, MD, Sunita
Trikha, MD, Nina S. Vincoff , MD, SyS!!n P, Weinstein , MD, Monica M. Y MD, S. Newell, MD
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MRI bte
contr
2
1
o D Ity occutt. Thi
mammography!
1 h primary beneftl of this procedure Is evaluat ng systemic dasease..
RRL
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EVALUATION OF RESPONSE
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• Clinical examination
• Mammography, including DBT
• Ultrasound
• MRI
• PET/CT
• MBI
L
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Com ents RRL
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, PET and PElleT should ilolft..:ll .r.-i rVt modal ttes.
used
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CLINICAL EXAMINATION
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• Overall accuracy 57%
• PPV 91%
• NPV 31%
• Limited for masses < 2 cm, dense tissue, fibrosis
• Unreliable after NAC for small early stage BC
Croshaw R, et al. Ann Surg Oncol 2011; 18:3160–3163 Keune JD, et al. Am J Surg 2010; 199:477–484
MAMMOGRAPHY
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• Variable accuracy
• Look for decreased size and density of mass
• Limited due to tumor necrosis, fibrosis, and fragmentation
• Tumor size only moderately correlated with residual
pathologic tumor size
• Calcifications can be misleading
• DBT useful
Chapgar AB et al. Ann Surg 2006;243;257-264
Andrada BE. Ann Surg Oncol 2015;22:1111-1117
ULTRASOUND
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• More accurate than mammography
• Still relies on size and morphology
• Not better at predicting pCR
• If both US and mammography negative, liklihood of
pCR 80%
Keune JD, et al. Am J Surg 2010; 199:477–484 Rauch GM et al. AJR 2017 Feb;208(2):290-299
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FUNCTIONAL IMAGING
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• Evaluate vascular, metabolic, biochemical and /or
molecular changes
• Occur earlier than morphologic changes
• Allow earlier assessment of response to NAC
• MRI, PET, MBI
MRI
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• Dynamic, contrast enhanced study
• Detects tumor angiogenesis, changes in
microcirculation, increased permeability of new
vessels
• Earlier and more accurate assessment of tumor
response
• Sensitivity 86-92%, specificity 60-89%, accuracy
76-90% for residual disease
Rauch,GM, et al. Multimodality Imaging for Evaluating Response to Neoadjuvant Chemotherapy in Breast Cancer. AJR 2017 Feb;208(2):
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MRI
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• Accuracy for estimating residual disease varies by
subtype
• Best in triple negative, HER2+, and high grade
tumors
• Highest sensitivity after 2 cycles of NAC
Fatayer H, et al. Eur J Surg Oncol 2016;42:965-972
MRI AFTER CHEMOTHERAPY- WHAT ARE WE LOOKING FOR?
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• Change in size of the known cancer
– Complete response
– Partial response
– Stable disease
– Progression of disease
• Change in enhancement pattern of known cancer
– Overall enhancement may decrease
– Decreased rate of initial enhancement and flattening of the kinetic curve
• Change in the size of axillary or internal mammary lymph nodes
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CAUSES OF MRI INACCURACY
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• Treatment related necrosis or fibrosis
• Antiangiogenic therapy can impair delivery of contrast to tumor foci
• Tumor shrinkage may be patchy with intervening necrotic areas
• Small foci of tumor may be scattered over a large area
• Receptor status (best in ER-/HER2+ and TN, worst in HER2-
and receptor positive cancers)
MR FALSE NEGATIVES
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• No residual enhancement on MRI, but the pathologic specimen
contains residual cancer
• HER2- cancers
• Hormone receptor positive cancers
• Tumors that present initially as non mass enhancement on MR
• Tumors that shrink to multiple tiny foci
• WARNING: residual disease may persist in spite of negative
imaging
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MR FALSE POSITIVES
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• Residual enhancement on MR, no residual
invasive disease at pathology
• Residual DCIS or hyperplasia
• Enhancement of normal tissue
• Scar, necrosis, fibrosis, benign lesions
ADVANCED MRI
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• Volumetric tumor measurement
• DWI- looks at diffusivity of water, cellularity, cell
membrane integrity-changes can predict response
• Texture analysis-quantitative measure of tumor
heterogeneity based on statistical modeling
• MR spectroscopy
• Multiparametric MRI
Hylton NM, et al. Radiology 2012; 263:663-672 Liu et al. JMRI 2015; 42:779-787
Rauch GM et al. 2017 Feb;208(2):290-299
FDG PET
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• Metabolic functional imaging
• Can show changes early in NAC
• Change in SUV after second course of NAC higher in patients with pCR
• Sensitivity 84%, specificity 66%, PPV 50%, NPV 91%
for early detection of response
• Limited detection of subcentimeter tumors and ILC
Andrade WP, et al. Eur J Surg Oncol 2013;39:1358-1363 Wang Y, et al. Breast Cancer Res Treat 2012; 131:357-369
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FDG PET
2/17/19 Rauch GM et al. AJR 2017 37
• Change in SUV of 55-65%
• More accurate after 1-2 cycles
• Affected by subtype – IDC, high grade, and triple negative, and HER2+ have
higher baseline uptake than ILC and low grade tumors
– Change in max SUV may be most helpful in triple neg, ER+,
and HER2- cancers
– Absolute max SUV after 2 cycles best for HER2+ BC
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ournal of Clinical Oncolo TBCRC026: Phase I I Trial Correlating Standardized
Uptake Value With Pathologic Complete Response
to Pertuzumab and Trastuzumab in Breast
Cancer
Roisin M. Connolly, MD1 0 ; jeffrey P. L l l i BA1 L.llja SOIW- MD1 Chlurut:Yu Huang_ ; ;
Ph01; Ashley Carpenter, MA1; Katy Gaffney, BSN1; Vandana Abramson, MD2; Usa A. Carey,
M03; Minetta c. Llu, Mo•; Mothaffar Rlmawl, M05; Jennifer Specht, MD6; Anna Marla
Stornlolo, MD7; VIcente Valero, MDa; Chrlstos Vaklavas, M09; Jan E. Kroe,. MD. Ph010; Eric P.
Winer, MD1o; Melissa Camp, MD1; RobertS. Miller, MD1; Antonio C. Wolff, MD1; Ashley M01; MD. Ph01; M011; and Vered Stearns,
No pCR
Baseline Follow-up
Images courtesy of Dr. Roisin Connolly
pCR
Baseline Follow-up Images courtesy of Dr. Roisin Connolly
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MOLECULAR BREAST IMAGING
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• 99mTc- sestamibi
• Uptake based on vascularity and mitochondrial
activity in tumor
• Similar sensitivity(88-95%) to MRI
• Better specificity(74-90%) than MRI
Guo C et al. Nuc Med Commun 2016;37:675-688 Mitchell D et al Clin Nuc Med 2013;38:949-956
AXILLARY NODAL IMAGING
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• Axillary pCR 40-75% with NAC
• Ultrasound useful both for imaging and biopsy
• Overall sensitivity for detection of mets 82%
• Specificity 96%
• Sensitivity for detection of node-positive disease post
NAC
– US 70%, PET/CT 63%, MRI 61%
• Axillary imaging does not preclude surgical staging
FUTURE DIRECTIONS
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• Imaging early during therapy to assess response
• Diffusion weighted MRI
• MR spectroscopy
• PET/MRI
• Ultrasound- elastography, contrast
• Contrast mammography
• MBI
• AI
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CONCLUSIONS
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• MRI is the most accurate study for monitoring
response to neoadjuvant chemotherapy
• FDG PET and other modalities may have a role
• Evolving literature regarding timing of imaging and which modality will be most useful
Thank you!
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REFERENCES
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• Slanetz PJ, et al. ACR Appropriateness Criteria: Monitoring Response to Neoadjuvant Systemic Therapy
for Breast Cancer. JACR 2017;14:S462-475.
Rauch GM et al. Multimodality Imaging for Evaluating Response to Neoadjuvant Chemotherapy in Breast
Cancer. AJR 2017 Feb;208(2):290-299
Croshaw R, et al. Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in determining
post neoadjuvant pathologic tumor response in operable breast cancer patients. Ann Surg Oncol 2011;
18:3160–3163
Keune JD, et al. Accuracy of ultrasonography and mammography in predicting pathologic response after
neoadjuvant chemotherapy for breast cancer. Am J Surg 2010; 199:477–484
Chagpar AB, Middleton LP, Sahin AA, et al. Accuracy of physical examination, ultrasonography, and
mammography in predicting residual pathologic tumor size in patients treated with neoadjuvant
chemotherapy. Ann Surg 2006;243:257-264
Hahn SY, Ko EY, Han BK, et al. Role of diffusion-weighted imaging as an adjunct to contrast-enhanced
breast MRI in evaluating residual breast cancer following neoadjuvant chemotherapy. Eur J Radiol
2014;83:283-288.
Fatayer H, Sharma N, Manuel D et al. Serial MRI scans help in assessing early response to neoadjuvant
chemotherapy and tailoring breast cancer treatment. Eur J Surg Oncol 2016 Jul;42(7):965-72.
Mitchell D, Hruska CB, Boughey JC, et al. 99mTc-Sestamibi Using a Direct Conversion Molecular Breast
Imaging System to Assess Tumor Response to Neoadjuvant Chemotherapy in Women with Locally
Advanced Breast Cancer. Clin Nuc Med 2013;38:949-956.
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