Role of PEM in Breast Cancer Management. Judy Kalinyak, MD, PhD Chief Medical Officer Naviscan, Inc (San Diego, CA)

Transcription

1 Role of PEM in Breast Cancer Management Judy Kalinyak, MD, PhD Chief Medical Officer Naviscan, Inc (San Diego, CA)

2 Role of PEM in Breast Cancer Management Introduction to Positron Emission Mammography PEM Clinical Imaging Pre-surgical planning Response to neo-adjuvant chemotherapy Recurrence monitoring PEM-Guided Biopsy Axillary Node Imaging Reduced Radiation Dose: data and images New (Non-Breast) Applications

3 Naviscan PET Scanner High (1.6 mm) intrinsic resolution Short 4-10 minute scan time Compact, portable, easy to use High Value 3-D tomographic PET images Gentle Immobilization vs. Compression FDA cleared and CE Mark approved scanner with breast biopsy guidance 3

4 PEM Images Acquired Like Mammograms Homogeneous FDG uptake in glandular tissue Pectoralis muscle Mammogram PEM Narayanan D, Madsen KS, Kalinyak JE, Berg WA. AJR Am J Roentgenol Apr;196(4):971-81

5 PEM is Tomographic Rmlo Medial Lateral Grade III IDC, multifocal Courtesy Mary Beth Lobrano, East Jefferson General Hospital, Metairie, LA

6 How Does PEM Help in Patient Management? Right Breast Cancer not seen with Mammography Ultrasound or MRI Left Breast Mammogram (X-ray Anatomic Imaging) 40 y/o female with area of increased density in the left inferior breast. Ultrasound biopsy found IDC and MRI confirmed single index cancer in left breast However, PEM found bilateral cancer: Left index cancer plus 2 small satellite cancers Right cancer - hidden in the upper outer quadrant Additional cancer lesions 6 PEM (Molecular Imaging)

7 How does PEM differ from Whole Body PET? Both Provide functional imaging and use FDG (fluorodeoxyglucose) PEM Optimized for small body parts Gentle immobilization Designed for patient comfort PET Whole Body Imaging 1-2 mm resolution 5-6mm resolution 7 Siemens Biograph 16 High Res PET/CT

8 Peer Reviewed Publications on PEM AJR: August 2011 Correlating PEM with Prognostic Indicators Predicting Survival Breast: August 2011 Imaging Sensitivity of PEM Superior to Whole-Body PET/CT AJR: January 2012 PEM Shows Strong Contralateral Lesion Visibility EJNM: November 2010 PEM in Breast Cancer Pre-surgical Planning: Comparisons with MRI AJR: April 2011 Interpretation of PEM by Experienced Breast Imaging Radiologists vs. MRI AJR: April 2011 Interpretation of PEM: Feature Analysis and Rates of Malignancy Breast: February 2011 PET-Guided Biopsy Radiology: December 2010 Comparative Effectiveness of PEM and MRI for Presurgical Planning of the Ipsilateral Breast in Women with Breast Cancer 8

9 NIH-Sponsored PEM-MRI Comparison Study Methods NIH funded*, multi-center, prospective clinical trial of 388 women with recent biopsy-confirmed in situ or invasive breast cancer Positive truth was histopathology or diagnosis of malignancy within one year of imaging Results 404 index tumors in 388 breasts, median size 1.5 cm Index Lesions MRI PEM MRI vs. PEM p-value Sensitivity 89.1% 344/ % 357/ * NIH Grant 5R44CA Berg W., et al.. Radiology 1:258 (2011) 9

10 NIH-Sponsored PEM-MRI Comparison Study Medial ipsilateral tumor size, 0.7 cm PPV of PEM-prompted biopsies (66%) versus MRI (53%), p= % women had unnecessary mastectomy: MRI prompted 5 unnecessary mastectomies PEM prompted 1 unnecessary mastectomy 8.5% (33) of women required wider excision: MRI identified 24 & PEM identified 22 Breast with Ipsilateral Cancer MRI (95% CI) PEM (95% CI) PEM vs MRI p-value PEM + MRI (95% CI) PEM+MRI vs MRI alone p-value Sensitivity 60.0% ( ) 51.0% ( ) % ( ) <0.001 Specificity 86.3% ( ) 91.2% ( ) % ( ) Accuracy 80.7% ( ) 82.7% ( ) % ( ) 0.56 * NIH Grant 5R44CA Berg 10 W., et al. Radiology 1:258 (2011)

11 PEM-MRI Site Investigator Results 1. PEM had 5% points greater specificity than Breast MRI, reducing false positives 2. PEM had comparable high MRI sensitivity 3. PEM had 14% points higher PPV than MRI, potentially reducing unnecessary biopsies 4. PEM was unaffected by Breast Density, Tumor Type, Menopausal or Hormonal Status providing significantly more precise Personalized Imaging than MRI. We looked very carefully for additional cancers and were surprised that barely half of these were shown on MR. PEM significantly improved detection of additional disease over MR alone Wendie Berg, M.D., Ph.D. and Principal Investigator * NIH Grant 5R44CA Berg W., et al. Comparative Effectiveness of PEM and MRI for Presurgical Planning of the Ipsilateral Breast in Women with Breast Cancer. Radiology 1:258 (2011)

12 The Power of Specificity PEM RCC True Positive MRI & PEM False Positive MRI True Negative PEM PEM LCC PEM RMLO Hx: 44 year-old with bilateral breast implants presented with abnormal mammogram. MRI: Bilateral masses suspicious for malignancy PEM: R irregular mass suspicious for malignancy, L breast normal. Pathology: R IDC; L benign fibrocystic change PEM LMLO Images courtesy James Rogers, MD, Swedish Medical Center, Seattle, WA

13 15% of Women Cannot Tolerate a Breast MRI* Study Summary: 1,215 women offered free screening breast MRI as part of ACRIN 6666 protocol MRI sub-study Results: 15% of eligible women not enrolled in study due to inability to tolerate breast MRI * Berg W., et. al. ACRIN AJR Jan

14 MONITORING RESPONSE TO NEO-ADJUVANT CHEMOTHERAPY

15 Neoadjuvant Chemotherapy Monitoring Day 0 Day 7 Day 14 PEM CC PEM can detect whether therapies are having an effect on patients EARLY within the first cycle of treatment! PEM MLO PEM is indicated as a biomarker to gauge progression of disease. Images courtesy of Mary K. Hayes, MD, Memorial Healthcare System, Hollywood, FL 15

16 Monitoring for Cancer Recurrence

17 PEM for Recurrent Cancer New IDC Recurrent Papillary Cancer 73 y/o with history of left papillary cancer treated with lumpectomy 12 years ago. Presented with abnormal right mammogram, biopsy found IDC. Right Left PEM was obtained for pre-surgical planning of right breast as the mammogram of the left breast was without change. PEM study showed FDG uptake in the right known cancer as well as in the left breast at the site of previous lumpectomy. PEM guided biopsy found RECURRENT LEFT PAPILLARY CANCER. 17 Images courtesy of Kathy Schilling, MD, Boca Raton Regional Hospital, Boca Raton, FL

18 PEM Pre-Surgical/Biopsy Planning CC Slice cm Right breast with 10 mm round mass in lower, outer quadrant, 8 cm from nipple. Lesion PUVmax is 6.6, Bkg PUVmean is 0.3, with a LTB ratio of Assessment 5, highly suggestive of malignancy. IDC grade III. BIRADS 3 should not be used with PEM!

19 PEM After Excisional Biopsy Excisional biopsy inflammation with seroma (PUVmax = 1.38) Tumor (PUVmax = 5.48) Skin biopsy site (PUVmax = 1.5)

20 PEM-Guided Biopsy

21 PEM-Guided Biopsy Patient Benefits Patient is upright, sitting FDA-Cleared, Commercially-Available Breast PET-Guided Biopsy Pillow for patient comfort Easier than MR for patients with back problems No claustrophobia 21

22 PEM-Guided Biopsy Visualize/Target Lesion Check Alignment Confirm Sampling Confirm FDG in Specimen First FDA-Cleared & Commercially-Available Breast PET-Guided Biopsy 22

23 Lymph Node Evaluation

24 Lymph Node/Axilla Evaluation Invasive ductal carcinoma in right breast. Level I lymph node suspicious for metastatic disease. Axillary imaging shows numerous lymph nodes with FDG uptake consistent with metastatic disease. Seven of 7 nodes were positive for cancer. Images Courtesy St. Louis PET Centers, Creve Coeur, Missouri

25 Evaluation for Loco-regional Spread Index cancer Axillary Mets 25

26 PEM Assessment of Axillary Lymph Nodes Purpose: Evaluation of metabolic imaging for identification of breast cancer metastatic disease in lymph nodes. Methods: 14 newly diagnosed breast cancer patients (13 IDC, 1 DCIS) underwent PEM axillary imaging. Biopsy of PEM suspicious nodes or sentinel lymph node biopsy with pathological analysis. Results: 5/14 pathology proven cancer metastasis in nodes. PEM identified 4/5 true positive (80% sensitivity), 0/9 false positive (100% specificity), PPV 100%, NPV 90%. Conclusion: PEM pilot study shows promising results for accurate lymph node assessment in breast cancer. Kulkarni, 26 Appelbaum, Sennett, Pu, Newstead; Univ of Chicago, ECR, March 2011

27 FDG DOSE REDUCTION

28 Steps to Reduce FDG Dose Simulation Study 50% coincident count reduction study showed no change in sensitivity for cancer detection, suggesting 5 mci dose is adequate. (SNM 2010 Annual Meeting) Physics Study Dr. MacDonald showed that FDG dose may be reduced down to 2 mci without loss of sensitivity (AAPM 2010 Annual Meeting) Clinical Study Swedish Cancer Institute s clinical trial showed same sensitivity with 5 mci dose in patients Now testing 2.5 mci (SNM 2011 Annual Meeting) as part of a company sponsored initiative

29 Simulated FDG Dose Reduction Study Design: Images reconstructed with 100%, 75% & 50% of coincident counts 100% 75% 50% Lu et al. SNM June 2010

30 Low Dose Clinical Images LC is a 37 year-old woman who had a non-diagnostic breast MRI due to cystic breast disease. PEM scan was performed with 5.3 mci imaged 60 min post injection with 10 min scan. Note the FDG uptake in lower, outer quadrant Bx found ALH. Surgery found LCIS+ADH+DCIS Images courtesy Kathy Schilling, MD, Boca Raton Regional Hospital, Boca Raton, FL

31 Low FDG Dose Images IDC GW is a 69 year-old, received 6.2 mci; 288 lbs; imaged 60 min post injection; 10 min scan IDC IDC papilloma SR is a 78 year-old, received 4.7 mci; 174 lbs; imaged 60 min post injection; 10 min scan Images courtesy Kathy Schilling, MD, Boca Raton Regional Hospital, Boca Raton, FL

32 Two Doses Same Patient Second 8 mm DCIS only seen and biopsied using PEM Index DCIS 10 cm from the nipple 8.5 mci 18 F-FDG (FDA recommended FDG dose is 5 10 mci) Images courtesy of Kathy Schilling, MD, Boca Raton Regional Hospital, Boca Raton, FL 3.2 mci 18 F-FDG History: 76 year-old, with a diagnosis of intraductal carcinoma intermediate grade (index DCIS) with necrosis and calcifications (inferior medial right breast). Patient underwent an initial PEM scan for preoperative staging. Findings: Two areas of uptake were identified on PEM ( 8.5 mci of 18 F-FDG), the index DCIS and an 8 mm lesion located 6.5 cm from the nipple. The patient was re-imaged 4 days later prior to biopsy using 3.2 mci of 18 F-FDG followed by PEM-guided biopsy. Pathology: DCIS.

33 Investigational Radiotracers: Cu year-old with 2+ invasive DCIS right breast. 3.9 mci Cu-64-TP3805 PEM obtained, 2 hr post injection. 12 mci F-18-FDG images obtained eight days later. Zhang K, et al. Profiling VPAC1 Receptors for Imaging Breast Cancer. SNM 2011 Abstract Presentation 33

34 NEW APPLICATIONS

35 Evaluating Peripheral Metastatic Disease 56 year-old metastatic breast cancer, progressive distal femoral lesion on bone scan easily measured using Naviscan Hi-Res PET Bone Scan WBPET/CT Scan Hi-Res Naviscan PET Scan 35

36 Squamous Cell Imaged with Hi-Res PET 69 year-old man with newly-diagnosed squamous cell cancer of the tongue base Whole Body PET/CT Hi-Res Naviscan PET Images courtesy of Eric Rohren, MD, PhD - MD Anderson Cancer Center 36

37 Melanoma Imaging with Hi-Res PET 85 year-old with hx melanoma, now presents with right toe lesion and question of recurrent cancer. PEM confirms recurrent melanoma. 37

38 Extremity Evaluation Note the anatomical detail in the PEM image showing the photopenic center from the dead cancer with only mild post-radiation inflammation. Hi-Res Naviscan Scan X-ray WBPET

39 Additional Uses for the Naviscan PET Scanner Breast PEM-guided microwave ablation Dermatology Melanoma Rheumatology Rheumatoid Arthritis Osteoarthritis Pediatrics Solid tumors (neuroblastoma, sarcoma) Neurology Alzheimer s Parkinson s 39

40 PEM Offers Imaging Versatility Axillary Imaging Imaging in women with Implants Dual Time Imaging PUVmax=2.52/Bkgmean=0.49 PUVmax=3.29/Bkgmean=0.34 LTB ratio=5.09 LTB ratio=

41 Thank you! Questions?