1. Assessing neoadjuvant chemotherapy (NAC) response in patients with breast cancer using PEM and DCE-MRI: Pilot data
Kirti Kulkarni MD, Daniel Appelbaum MD, Charlene Sennett MD, Yonglin Pu MD, Bill O’Brien Penney PhD and Gillian Newstead MD, FACR
University of Chicago Medicine, Department of Radiology
Section of Breast and Nuclear Medicine
Chicago, IL, USA
Contact:

2. Purpose
PEM is a promising functional based tool to predict “true” functional/metabolic response of breast cancer to NAC
This helps us ascertain the final tumor burden which is a pivotal prognostic factor in breast cancer patients
To introduce the concept of using PEM as an additional dimension to our standard of care imaging modalities for breast cancer
Can PEM be an early precursor to NAC response in comparison with MRI?

3. Concept: PEM vs. MRI
Fig 1: Molecular imaging has the advantage of not being dependent on capillary angiogenesis
FDG can diffuse into the interstitial space and be taken up by the abnormal cancer cells. FDG is ideal because of the increase uptake in cancer, and the fact it remains trapped in the cancer cell while normal cells release and the kidneys clear excess, reducing background tissue levels.
Metabolically trapped
PEM MRI Mammography

4. Materials IRB approved prospective study n=2 (mean age 55 yrs)
Inclusion criteria: Diagnosis of breast cancer (2 Infiltrating ductal carcinoma, grade 3, triple negative with axillary lymph node metastasis) on NAC
Mean cancer size = 2 cm
All patients underwent mammography, breast and axillary ultrasound, breast MRI (1.5 T Phillips scanner) and PEM (Naviscan inc. ); 1 prechemotherapy and 2 post chemotherapy scans performed
Final tumor burden status was determined pathologically at the time of breast surgery and graded as: (1) UNDERESTIMATION of residual tumor size: (<70% of the size on pathology)
(2) EQUAL to: (longest diameter is upto 30% of the size at pathology
(3) OVERESTIMATION of residual tumor size: (>130% of the size on pathology)

5. Methods Patient fasting for 4-6 hours before the examination
Fasting blood glucose level (< 150 mg/dL)
Injection of 10 mCi of 18-FDG in the foot or contralateral arm
PEM scan mins after the injection
Baseline 90 second scan of injection site / arm (for quality control)
10 min each for bilateral CC and MLO views
Additional bilateral axillary views, 10 min each
Fig. 2: -Principles of PET imaging -High density crystals in a parallel array with close
proximity to the breast -Reiterative reconstructions to eliminate
background noise –Fast timing collimation -High count rate

6. DCE-MRI and PEM <14 days apart
Methods
DCE-MRI and PEM <14 days apart
Order of DCE-MRI or PEM is randomized
Diagnosis of Breast Cancer
Candidate for NAC
Imaging 0 (baseline)
Baseline DCE-MRI + PEM
1 to 2 weeks
Imaging 1
DCE-MRI + PEM
Positive response
+ MRI MRI
+ PEM PEM
Breast Conservation Therapy
1 to 2 weeks
Mastectomy
- MRI MRI
- PEM PEM
Imaging 2 (Pre-op)
DCE-MRI + PEM
Negative response OR
Change in NAC
Quantification of POSITIVE RESPONSE to NAC on DCE-MRI/ PEM:
1. Percentage Reduction in maximum diameter of tumor
GOLD STANDARD IS PATHOLOGY

7. Results
PEM and MRI studies interpreted by consensus of 2 radiologists --Subjective analysis based on intensity of uptake categorized as: none, minimal or significant --Quantitative analysis: PEM: size and maximum PUV uptake value MRI: size of tumor and kinetic response
Reduction in size of tumor and ALN
Pathology
tumor burden
PEM
96%
95%
MRI
91%
Table 3: PEM and MRI results compared to the gold standard

8. Left lower inner quadrant
Fig 4: 50 year old with palpable mass in left breast. Mammogram shows a 3 cm
irregular mass in left lower inner quadrant which was biopsy proven IDC with
metastatic axillary LN.
Abnormal enlarged
left axillary LN
Palpable
Mass
Left lower inner quadrant
L MLO
L CC

9. Fig 5: Pre chemotherapy vs. Post chemotherapy MRI and PEM demonstrating
almost complete response on MRI and PEM study.
PRE
PRE
MRI pre chemo: angiomap
Area of increased uptake in left breast and axilla
POST
POST
No uptake in left breast and minimal uptake in axilla
MRI post 1 cycle chemo: angiomap

10. Fig. 6: PEM scan Left CC, MLO views, with PUV quantitative analysis

11. Pre and Post chemotherapy day 0, 1 week and 2 weeks post NAC
PEM CC
PEM Findings:
PEM shows significant reduction in lesion size two weeks following start of therapy indicating partial response to therapy.
PEM
MLO 11

12. Conclusion
Preliminary PEM data shoes promising results in more accurate assessment of final tumor burden after NAC.
Plays a pivotal role in assessing axillary lymph node staging
PEM has the potential as an additional tool in the overall breast multimodality CAD system.
PEM can perhaps be an early precursor to NAC response in comparison to DCE-MRI

13. References
Lovrics PJ, Chen V, Coates G, et al. A prospective evaluation of positron emission tomography scanning, sentinel lymph node biopsy, and standard axillary dissectionfor axillary staging in patients with early stage breast cancer. Ann Surg Oncol2004;11: Berg WA, Weinberg IN, Narayanan D, Lobrano MB, Ross E, Amodei L, et al. High Resolution FDG Positron Emission Tomography with Compression ("Positron Emission Mammography") is Highly Accurate in Depicting Primary Breast Cancer. Breast J 2006;12(4):309-23