Spatial mismatch in CT-defined vs. NaF PET-defined lesions: implications for diagnostic bone biopsies

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1 Spatial mismatch in CT-defined vs. NaF PET-defined lesions: implications for diagnostic bone biopsies Stephanie Harmon, Song Chen, Peter Ferjancic, Timothy Perk, Michael Tuite, and Robert Jeraj University of Wisconsin Madison, WI, USA

2 Musculoskeletal Disease Metastatic spread to bone is common in various types of cancer, including breast and prostate Accurate diagnosis of musculoskeletal tumors is important for successful treatment, tissue sample required Rajarubendra 2010 Musculoskeletal metastases provide a clinical challenge Small volumes Deep seeded, commonly occurring in pelvis, spine and ribs Osteoblastic lesions increase bone formation (sclerotic) Osteolytic lesions break down bony matrix (lytic) Wu 2008, Puri 2006, Rimondi 2011

3 Diagnostic Sampling of Disease Gold standard for diagnostic biopsy: CT guidance Rimondi 2011 Overall diagnostic yield accuracy ~80% Altuntas 2005, Wu 2007 Accuracy dependent on disease mechanisms Lytic lesions show superior target accuracy (90%+) Sclerotic lesions often have poor yield, with decreased accuracy (~50%) and 24% false positive rate Lis 2004, Tehranzadeh 2007

4 What the IR sees

5 What the IR sees Physician CT contour

6 What the IR sees: post-biopsy Physician CT contour

7 Metastatic Prostate Cancer (mpc) Osteoblastic (sclerotic) lesions are dominant in mpc Aggressive bone formation Reactive sclerosis of surrounding bone Hwang 2011 Molecular Imaging can provide functional view of disease Increased sensitivity of disease identification when using [ 18 F]FDG PET/CT compared to CT alone Klaeser 2009

8 Metastatic Prostate Cancer (mpc) Osteoblastic (sclerotic) lesions are dominant in mpc Aggressive bone formation Reactive sclerosis of surrounding bone Molecular Imaging can provide functional view of disease Increased sensitivity of disease identification when using [ 18 F]FDG PET/CT compared to CT alone [ 18 F]NaF PET/CT has shown superior specificity and sensitivity in detecting bone lesions compared to all other modalities Morrison 2013

9 NaF PET/CT Physician CT contour

10 PET Contours Physician CT contour NaF PET

11 Post-biopsy CT Physician CT contour NaF PET

12 Study aim Hypothesis Spatial mismatch between functional tumor volume and sclerotic tumor volume leads to poor diagnostic accuracy in CT-guided musculoskeletal biopsies

13 Study aim Hypothesis Spatial mismatch between functional tumor volume and sclerotic tumor volume leads to poor diagnostic accuracy in CT-guided musculoskeletal biopsies Aim of Preliminary Study Quantify functional and anatomical differences in PET-defined vs. CT-defined bone lesions

14 Methods- Patient Imaging 9 metastatic castrate-resistant prostate cancer patients NaF PET/CT Received [ 18 F]NaF PET/CT at UWHC prior to beginning treatment

15 Methods- Lesion Segmentation 9 metastatic castrate-resistant prostate cancer patients NaF PET-defined Received [ 18 F]NaF PET/CT at UWHC prior to beginning treatment Identification of targetable lesions Locations of interest: Pelvis, Sacrum, Lumbar Spine, and Femurs PET segmentation 15 SUV threshold in skeletal regions CT segmentation Manual physician contouring CT-defined

16 Methods- analysis Dice Similarity Coefficient to assess spatial and volumetric cooccurence of PET and CT volume ROIS A - PET ROI B - CT ROI A B Investigation of imaging characteristics Across modality-defined volumes Within region of overlap In PET-only regions In CT-only regions

17 Comparison of modality-defined lesions Patient Total volume (cm 3 ) Number of Lesions PET-defined CT-defined PET-defined CT-defined All

18 Comparison of modality-defined lesions Patient Total volume (cm 3 ) Number of Lesions PET-defined CT-defined PET-defined CT-defined NaF PET-defined All CT-defined

19 Comparison of modality-defined lesions Individual lesion sizes Patient Total volume (cm 3 ) Number of Lesions PET-defined CT-defined PET-defined CT-defined All

20 Imaging Characteristics: PET vs. CT Areas of higher sclerosis are involved in both lesions Areas of high bone metabolism also in both lesions, but more pronounced in PET-defined lesions p<1e-8

21 Sclerotic Characteristics: PET vs. CT Are areas of high sclerosis where PET and CT overlap?

22 How well did lesions overlap? A B A - PET ROI B - CT ROI Dice Coefficient PET-defined (N pet ) CT-defined (N ct ) Matched Average (%) Range (%) All

23 Sclerotic Characteristics: sub-region analysis A B A - PET ROI B - CT ROI

24 Sclerotic Characteristics: sub-region analysis A B A - PET ROI B - CT ROI PET-defined only CT defined only

25 Sclerosis in PET vs CT lesions Dice Similarity Coefficient relates both spatial size and cooccurrence and heavily influenced by larger of two volumes B A B A A - PET ROI B - CT ROI

26 Sclerosis in PET vs CT lesions Dice Similarity Coefficient relates both spatial size and cooccurrence and heavily influenced by larger of two volumes Overlap Volume does not have this bias B A B A A - PET ROI B - CT ROI

27 Overlap characteristics Lesions with moderate overlap show more sclerosis High Overlap: ov>80% Moderate Overlap: 80%>ov>50% Poor Overlap: ov<50%

28 Summary 132 lesions were automatically segmented on NaF PET/CT in 9 metastatic prostate cancer patients 109 identified independently by physician on CT only 96 showed spatial co-occurrence Lowest amount of sclerosis was noted in the PET-avid portion of co-occuring volumes Could indicate new/active disease region CT-defined volumes exhibited significantly more sclerosis Potential biopsy targets should consider functionally active disease subvolumes to maximize accuracy

29 Summary Thank You! Questions?