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: kkulkarni@radiology.bsd.uchicago.edu

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?

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

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)

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 60-90 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

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

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

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

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

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

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

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

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;11:846-853. 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