Download Michael F. McNitt-Gray, PhD: CT imaging as a biomarker: the role of

Michael F. McNitt-Gray, PhD: CT imaging as a
biomarker: the role of CT in evaluating lung
cancer treatment efficacy
May 15, 2008- 8:40 AM
CT Imaging as a Biomarker:
The Role of CT in Evaluating Lung Cancer
Treatment Efficacy
The Role of CT in Lung Cancer
„
Screening/ Early Detection
„
Characterization/Diagnosis
– low dose CT to detect early stage disease
Michael F. McNitt-Gray, PhD
Professor
Department of Radiological Sciences
Director
Biomedical Physics Graduate Program
David Geffen School of Medicine at UCLA
Characterization Task
„
IDEAL Goal of Characterization
– Distinguish cancers (Malignancies) from
non--cancers (Benign)
non
– Further Distinctions Possible? Different
Types of Lung Cancers?
– Characterize detected lung nodules as benign or
malignant (false positives)
„
– Is patient responding to treatment? How can you
tell? Look for change on CT
– Especially important for evaluating new
therapeutic agents (e.g. clinical trials)
Characterization Task - Approaches
1. Change Over Time (Multiple Exams)
„
Currently, for Nodule characterization,
dynamic CT imaging with contrast
enhancement is used
„
Measure Average Attenuation within ROI
„
Then measure Enhancement
Enhancement::
–
–
Determine Boundary of the Nodule
Measure Volume or Some Density Measure
–
–
–
–
–
Density
Size
Shape
Texture
Contrast Enhancement, etc.
2. Single Exam to Evaluate Image
Characteristics such as:
– Adenocarcinoma from bronchiolaveolar carcinoma?
– Aggressive from indolent tumors?
Background
Treatment Response
Lung Nodule Enhancement
Injection of Contrast
at t=0 s
Enhancement =
[ROI mean (Max post contrast)] – [ROI mean(0
mean(0)]
Stanford Radiology 10th Annual Multidetector
CT Symposium
t<0 s
t=45s
t=90s
t=180s
t=300s
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Michael F. McNitt-Gray, PhD: CT imaging as a
biomarker: the role of CT in evaluating lung
cancer treatment efficacy
May 15, 2008- 8:40 AM
Treatment of Lung Cancer
Lung Nodule Enhancement
„
Number of Ndules at Each
Enhancement Level
„
Almost all cancers
show enhancement
(increased blood
supply)
l )
Many benign
processes show
enhancement as
well
„
„
Nodule Enhancement in HU for Benign and Malignant
Nodules
35
– Are they responding to treatment?
– How can we know this?
If Enhancement <20, then B
If Enhancement > 20, then ?
30
25
20
Benign
15
Malignant
For Patients with known lung cancer or
disease that is metastatic to the lung
Key question is
10
5
6
14
8
16
0
17
2
13
88
10
0
11
2
12
4
40
76
52
64
-8
28
4
16
-2
0
0
Enhancement in HU
Evaluation Criteria using CT
„
„
Assess response by looking for **CHANGE
**CHANGE**:
**:
Currently
– Assess changes in Morphological Measures - Size
– Unidimensional diameter measurement
„
RECIST-- next slide
RECIST
– Bidirectional diameter measurements
„
Future
RECIST
„
– Longest Diameter of lesion
„
„
„
– Assess change in size using tumor volumes
– What about change in other measures/characteristics
„
„
„
„
Unidimensional measurement
Up to 5 lesions
E
Easy
to iimplement
l
May be unreliable estimate of change
–
–
–
–
Mass
Density
Shape
Function?
difficulty in estimating irregular lesions
discrepancies in scan planes between scans
patient positioning differences between scans
intraintra- and interinter-observer variability
Determining Response
„
Tumor is clearly getting smaller
– Will a single diameter reflect this?
– How can me measure this:
„
„
„
Stanford Radiology 10th Annual Multidetector
CT Symposium
Accurately (do we know the “truth”?)
Precisely (how reproducible?)
Can we determine whether this tumor
is responding at some point earlier
than 52 weeks?
2
Michael F. McNitt-Gray, PhD: CT imaging as a
biomarker: the role of CT in evaluating lung
cancer treatment efficacy
May 15, 2008- 8:40 AM
Determining Response
„
„
„
How do we know the change we are
seeing is real change and not just
measurement variability?
What is the minimum amount of
change we can detect?
How long would it normally take to
see this minimum detectable change?
Baseline
Max Diameter = 36.2 mm;
Baseline + 20 weeks,
Max Diameter = 32.6 mm
(10% decrease)
Would be characterized as
stable/no change
(30% decrease is required
to classify as regression);
– A few weeks? Months?
Response
„
„
Baseline
Max diameter = 36.2 mm;
Baseline + 20 weeks,
Max diameter = 32.6 mm;
Tumor volume= 6.10 cm3
tumor volume= 9.48 cm3,
a 55% increase
Current/Future Research Areas
„
„
Moving from anatomic description
(size, shape, location) to function
Fusion with other imaging modalities
(PET--CT)
(PET
Patient Response is not so clear here
RECIST (single diameter of lesion) is
not full information here
CT Imaging of Contrast Agent
„
Obtain images through nodule
– Prior to injection of contrast agent (T=0)
– Obtain images at 4 points after contrast
injection
„
„
Stanford Radiology 10th Annual Multidetector
CT Symposium
T=45, 90, 180 and 300 sec
4D map of contrast enhancement
3
Michael F. McNitt-Gray, PhD: CT imaging as a
biomarker: the role of CT in evaluating lung
cancer treatment efficacy
T=45
T
45
T=180
T=90
T
90
T=300
Dynamic Imaging Protocol
„
„
Instead of 4 time points post contrast
More rapid imaging
Quantitative measurement
Tumor TimeTime-Attenuation Curve (TAC)
ƒPlot average
intensity of 2D
ROI vs time
60
45, 53.16070773
Net Enhancementt(HU)
T=0
T
0
May 15, 2008- 8:40 AM
– Up to 2020-25 time points
40, 48.13276675
35, 47.46169323
50, 45.96992082
40
94, 36.94143436
142, 36.37639939
172, 32.76206526
25, 32.10861385
24,30.663381
31.06844726
22,
05
21, 28.22116968
201, 28.14162955
18, 26.25342774
23, 26.08477023
20, 25.46742241
19, 23.14017812
17, 22.06122712
261, 22.60579333
20
16, 17.60569944
15, 9.944659313
0
0, 0
0
PET/CT fused images
50
100
150
Time(s)
200
250
Summary
„
CT is being used in several ways in
regards to Lung Cancer
– Screening (early detection)
– Characterization (distinguish between
benign and malignant)
– Treatment response
Stanford Radiology 10th Annual Multidetector
CT Symposium
4
Michael F. McNitt-Gray, PhD: CT imaging as a
biomarker: the role of CT in evaluating lung
cancer treatment efficacy
May 15, 2008- 8:40 AM
Future Investigations
„
Can CT be used as a biomarker
– Can it tell if image data indicates a
response
p
to therapy?
py
Does volume change? Does density change?
Some other change that can be measured
reliably, such as function (contrast uptake)?
„ Fusion with other modalities (PET
(PET--CT)
„ What will it take to determine if change is
significant?
„
„
Stanford Radiology 10th Annual Multidetector
CT Symposium
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