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Motivation
Triple-Negative Breast Cancer 15% of all breast cancers; 30,000 annual diagnoses; 8000 deaths Lacks estrogen, progesterone, HER2 receptors Response to chemo is mixed
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Motivation
Triple-Negative Breast Cancer 15% of all breast cancers; 30,000 annual diagnoses; 8000 deaths Lacks estrogen, progesterone, HER2 receptors Response to chemo is mixed Critical Need A way to predict in advance whether patients will respond: Precision Medicine
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Motivation
Triple-Negative Breast Cancer 15% of all breast cancers; 30,000 annual diagnoses; 8000 deaths Lacks estrogen, progesterone, HER2 receptors Response to chemo is mixed Critical Need A way to predict in advance whether patients will respond: Precision Medicine
Known Malignancy Selection of Optimal Treatment
???
Daniel Golden (dgolden1@stanford.edu) Breast Cancer Imaging Biomarkers
Treatment A Treatment B
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Motivation
Dynamic Contrast-Enhanced MRI (DCE-MRI) Acquires multiple images before and after contrast injection Whole tumor, minimally-invasive (unlike biopsy) Reveals tumor kinetic phenotype: morphology and texture Hypothesis: Features can predict treatment response
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Motivation
Dynamic Contrast-Enhanced MRI (DCE-MRI) Acquires multiple images before and after contrast injection Whole tumor, minimally-invasive (unlike biopsy) Reveals tumor kinetic phenotype: morphology and texture Hypothesis: Features can predict treatment response
Known Malignancy Selection of Optimal Treatment
???
Daniel Golden (dgolden1@stanford.edu) Breast Cancer Imaging Biomarkers
Treatment A Treatment B
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Motivation
Dynamic Contrast-Enhanced MRI (DCE-MRI) Acquires multiple images before and after contrast injection Whole tumor, minimally-invasive (unlike biopsy) Reveals tumor kinetic phenotype: morphology and texture Hypothesis: Features can predict treatment response
Known Malignancy MRI Features Selection of Optimal Treatment
???
Daniel Golden (dgolden1@stanford.edu) Breast Cancer Imaging Biomarkers
Treatment A Treatment B
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Outline
Imaging Biomarkers
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Outline
Imaging Biomarkers
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List of Features
Semantic Imaging Breast Imaging Reporting and Data System (BI-RADS) Quantitative Imaging Lesion kinetic texture via the Gray-Level Co-Occurrence Matrix (GLCM) Both assessed prior to chemotherapy
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List of Features
Semantic Imaging Breast Imaging Reporting and Data System (BI-RADS) Quantitative Imaging Lesion kinetic texture via the Gray-Level Co-Occurrence Matrix (GLCM) Both assessed prior to chemotherapy
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Gene-expression signatures of good and poor prognosis were detected in different regions of the same tumor.
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10 mm
1000
Image 800 Intensity 600
Wash-Out Wash-In
400 0 2 4 6 8 Minutes 10 12 14
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10 mm
1000
Image 800 Intensity 600
Wash-Out Wash-In
trans
(min )
2 1.5 1
400 0 2 4 6 8 Minutes 10 12
140.5
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Pixel Amplitude
4 6 8 2
Pixel Amplitude
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Num Pixels
Pixel Amplitude
4 6 8 2
Pixel Amplitude
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Num Pixels
GLCM
2000
Pixel Amplitude
4 6 8 2
Pixel Amplitude
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Num Pixels
GLCM
2000
Outline
Imaging Biomarkers
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Residual Tumor
Residual Nodes
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Residual Tumor
Residual Nodes
Resid Tumor + Nodes 0.5 0.6 0.7 ROC AUC 0.8 0.9 1
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GLCM
Residual Tumor
Residual Nodes
GLCM BI-RADS
0.9
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Outline
Imaging Biomarkers
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Thank You
Mentor Daniel Rubin Collaborators Ja Lipson Melinda Telli Jim Ford Katie Planey Nick Hughes Funding Stanford SCIT Program (NIH T32 CA009695) NIH U01 CA142555
Daniel Golden (dgolden1@stanford.edu) Breast Cancer Imaging Biomarkers Mar 1822, 2013 15 / 14
Malignancy Sinha et al., 1997; Chen et al., 2007; Woods et al., 2007; Kale et al., 2008; Nie et al., 2008; Agner et al., 2011; Karahaliou et al., 2012 Hauth et al., 2008; Preim et al., 2011
Survival
Type
Treatment Response
Texture
Histogram
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Malignancy Sinha et al., 1997; Chen et al., 2007; Woods et al., 2007; Kale et al., 2008; Nie et al., 2008; Agner et al., 2011; Karahaliou et al., 2012 Hauth et al., 2008; Preim et al., 2011
Survival
Type
Treatment Response You Are Here Chang et al., 2004; Padhani et al., 2009
Texture
Histogram
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good response
BIRADS NonMass BIRADS Mass Margin Spiculated BIRADS Mass Enhancement Homogeneous BIRADS Mass Shape Round 1 0.5 0 b*std
poor response
0.5
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Data Set
The Triple-Negative Breast Cancer (TNBC) Trial Clinical trial run by Melinda Telli and Jim Ford at Stanford 93 patients with triple-negative or BRCA-mutated breast cancer 69 patients available for analysis This imaging study: retrospective and proof-of-concept
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Non-Imaging Features
Clinical Age at diagnosis Tumor stage (IAIIIA) Tumor grade (II or III) T and N stage from TNM (T0T4, N0N3) ER/PR percent (for non-triple-negative) Ki67 percent Cycles of treatment received (4 or 6) Genomic BRCA 1/2 mutation status
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Kinetic Modeling
t=1.5 min
1 cm
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Kinetic Modeling
t=1.5 min
3
Fractional enhancement
2 1 0 1 0
Data Model
1 cm
Minutes
10
15
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Kinetic Modeling
t=1.5 min
3
Fractional enhancement
2 1 0 1 0
K (min1)
ep
Data Model
1 cm Ktrans (min1)
Minutes
10
ve (unitless)
15
3
2 1.5 1 0.5
2 1.5 1 0.5
0 2
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Lasso
Feature Sets
All Clinical All Clinical but Ki67 Ki67 GLCM Pre GLCM Post GLCM Pre and GLCM Post Patterns of Response BIRADS GLCM Pre and BIRADS
Lasso Model
Response
Residual Tumor Residual Lymph Nodes Residual Tumor and Nodes
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junk junk
junk junk
junk junk junk 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
AUC 95% CI
junk junk
junk
junk
Model Features
Relevant features for predicting Residual Tumor
PostChemotherapy GLCM 0.5 0.75 1 AUC
Postchemo GLCM Kep Correlation Postchemo GLCM Ktrans Correlation Postchemo GLCM ve Homogeneity Postchemo GLCM WashIn Energy Postchemo WashOut Average 1 0 b*std 1
Postchemo GLCM Kep Correlation Postchemo GLCM Ktrans Correlation Postchemo GLCM WashIn Energy Postchemo GLCM Kep Contrast Postchemo WashOut Average 1
Daniel Golden (dgolden1@stanford.edu)
0 b*std
1
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Model Features
Relevant features for predicting Residual Lymph Nodes
Clinical All 0.75 GLCM Pre and PostChemotherapy 0.5 0.75 1 AUC
0.5 AUC Tumor Stage IIIA BRCA1 Negative Treatment Cycles: 4 Age Tumor Grade II TNM: N1 Treatment Cycles: 6 BRCA1 Positive Ki67 percent TNM: N0 1
Prechemo GLCM Kep Homogeneity Postchemo Lesion Area Postchemo GLCM Ktrans Correlation Prechemo GLCM Kep Contrast 1 0 b*std
BIRADS 0.75
0 b*std
0.5 AUC BIRADS NonMass BIRADS Mass Margin Spiculated BIRADS NonMass Segmental BIRADS Mass Enhancement Homog. BIRADS Mass Margin Smooth BIRADS Mass Shape Round 1
0.5 AUC Tumor Stage IIIA BRCA1 Negative Age Treatment Cycles: 4 TNM: N1 TNM: N0 1
0 b*std
0 b*std
Prechemo GLCM Kep Energy Prechemo GLCM Contrast AUC Energy Prechemo GLCM Ve Contrast Prechemo GLCM Kep Contrast 2 0 b*std 2
BIRADS NonMass Prechemo GLCM Contrast AUC Energy Prechemo GLCM Kep Energy Prechemo GLCM Kep Homogeneity Prechemo GLCM Ktrans Homogeneity BIRADS Mass Margin Spiculated BIRADS NonMass Enhancement Homog. BIRADS NonMass Segmental BIRADS Mass Shape Round Prechemo GLCM Kep Contrast 2 0 b*std 2
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Model Features
Relevant features for predicting Residual Tumor and Lymph Nodes
Clinical All 0.75 BIRADS 0.75
0.5 AUC Tumor Stage IIIA Treatment Cycles: 4 Tumor Grade II BRCA1 Negative TNM: N1 Age Treatment Cycles: 6 TNM: N0 Ki67 percent 1
0.5 AUC BIRADS NonMass BIRADS Mass Margin Spiculated BIRADS NonMass Enhancement Homog. BIRADS NonMass Segmental BIRADS Mass Enhancement Homog. BIRADS Mass Shape Round 1
0 b*std
0 b*std
BIRADS NonMass BIRADS Mass Margin Spiculated Prechemo GLCM Contrast AUC Energy Prechemo GLCM Ktrans Homogeneity Prechemo GLCM Kep Energy Prechemo GLCM Kep Homogeneity Prechemo GLCM Ktrans Energy BIRADS NonMass Segmental BIRADS NonMass Enhancement Homog. Prechemo Contrast AUC Average BIRADS Mass Enhancement Homog. BIRADS Mass Shape Round 1 0 b*std 1
Postchemo GLCM Ktrans Correlation Postchemo Lesion Area Prechemo GLCM Kep Energy 1 0 b*std 1
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Model Features
Relevant features for predicting No Residual Tumor
GLCM Postchemotherapy 0.5 0.75 1 AUC
Ki67 0.75
GLCM Ktrans correlation postchemo GLCM wash out slope contrast postchemo avg wash out postchemo 1 0 b*std 1
0 b*std
0.5
GLCM Ktrans correlation postchemo GLCM AUC contrast prechemo GLCM kep contrast postchemo GLCM wash out slope contrast postchemo avg wash out postchemo 1 0 b*std 1
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2 3 RCB Value
5 4
5
6 5
5
4
RCB
3
2 3 2 1 4
1 1 0.5 0 0
2 1
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