day 1 - thursday - 0830 am - rick avila
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Controlling Variability in Lung Cancer Response AssessmentRicardo S. AvilaMay 13, 2010
Therapy AssessmentCharacteristics Late stage Thick Slice CT
Assessment Tumor response ID new lesions ?
Tumor Size
4 cm lesion
t ? TimeStart Therapy Assess Response
RECIST8mm D, 13 pixels 73% Volume
Target Lesion Measurement RECIST: Sum of LD
Progressive Disease
D = +20%Unaided Interpretation
Stable Diseaseweeks
4cm lesion
D = -30%
Partial Response
TimeBaseline & Treat
Complete Response
Erasmus et. al., JCO 2003 Intra-observer error PD: 9.5% of tumors PR:3% of tumors Inter-observer error PD: 30% of tumors PR: 14% of tumors
Assess Response
We Can Do BetterTarget Lesion Measurement RECIST: Sum of LDProgressive Disease
Improve Accurac y Precisio n To Improve Interval (Dt) Study NAided 3D Interpretation
t TimeEarly Detection & Nodule Sizing
Complete Response
Partial Response
Stable Disease
4cm lesion
Detecting a 50 Micron Displacement
Patton and Byron Nature Reviews Drug Discovery 2007
Computed TomographySiemens Emotion 16 16 Slice Scanner 1.00mm Slice Thickness
B30s Kernel
B60s Kernel
GE LightSpeed Ultra 8 Slice Scanner 1.25mm Slice Thickness
Very Low Dose
Low Dose
Measurement Challenges
Patient/Lesion Presentation Size Complexity Changes over time (necrosis)
Scanners Hardware (collimation) Software (releases)
Protocols ScanRx Contrast Patient position
Observer Seed points/ROI Data Interpretation5mm 2.5mm
Volumetric Algorithm ChallengesBoundary Identification ChallengesNo/Small I
Vascular network (Ev) Bronchial network (Eb) Pleura (Ep) Sub-voxel edge (Es)
Errors at 2 time points
Ev
Volumetric error strongly depends on lesion size and slice thickness
Ep EsPl e ur a
Technical Focus Areas Open Image Archives LCAs Give-A-Scan Project OSAs Interactive Science Publishing RSNAs Ad Hoc Committee on Open Image Archives
Understanding Measurement Performance Benchmarks: NIST Biochange and Volcano QIBA: Phantom Data Studies QIBA: Measurement Performance on Clinical Data Kitware Pocket Phantom
Open Source Algorithms and Models Lesion Sizing Toolkit COPD Modeling and Quantification
Establishing Standards for Clinical Trials QIBA: Volumetric CT Profiles
Quantitative Identification of Patient Sub-Populations
Analysis of imaging and clinical data can potentially identify patient populations that respond more favorably to lung cancer therapy
Drug Efficacy Lung Damage Assessment COPD impacts aerosolized drug delivery Lung Cancer Risk
Safety Cardiovascular damage
Lung Cancer Alliances Give-A-Scan Project
A Lung Cancer Alliance Project Pilot project started in 2008 Process and procedures were created for accepting and anonymizing datasets ~30 individuals expressed interest in participating 17 scans received, but 2 were not readable Over 6 GB of image and meta data was collected 9 patient scans have been prepared for public dissemination on a LCA website.
Give-A-Scan WebsiteDataset includes: Age Gender Cancer Type Cancer Stage Family History
4 of the 9 subjects are never smo
Legal DocumentsA large amount of effort spent on developing the legal framework Informed Consent End User License
An open set of legal resources for open image archives would benefit many projects
New CT Pocket Phantom
New CT Pocket Phantom
Goal: To characterize the fundamental imaging characteristics of CT acquisitions performed in the Roche ABIGAIL study 3D Resolution & Sampling Rate Noise Characteristics X-ray Attenuation Performance
Acrylic
Delrin
Teflon
Urethane
New CT Pocket Phantom Manufactured 21 phantoms and deployed them into the Abigail phase II clinical trial
Fully Automated Phantom Analysis
Several Studies UnderwayResolution vs. Distance to IsocenterIn-Plane PSF = 0.53 mm D = 112 mm = 0.45 mm = 0.47 mm = 0.54 mm D = 49 mm D = 62 mm D = 118 mm
= 0.53 mm = 0.45 mm = 0.44 mm = 0.51 mm D = 114 mm D = 43 mm D = 32 mm D = 104 mm
Standard Kernel Bone Kernel Lung Kernel
Comparison of the New Pocket Phantom with a Catphan Phantom
Calibration Study Siemens Sensation 64 CT Scanner 6 pocket phantoms placed in/near an anthropomorphic chest phantom Catphan phantom also scanned Varied slice thickness, mA, kVp, and pitch
Pearsons Correlation Coefficients CT Density = 0.999 (P < 0.001) Noise = 0.940 (P < 0.001) Resolution = 0.929 (P < 0.001)
Open Source Lesion Sizing Toolkit
The Lesion Sizing Toolkit
http://public.kitware.com/LesionSizingKit/
The Lesion Sizing Toolkit (LST) is a free and open source software architecture designed to accelerate the development and evaluation of quantitative lesion sizing algorithms.
Developed in 2008 Focused on Dissemination in 2009RSNA Quantitative Reading Room of the Future Showcase Open Source Medical Imaging Software Course Benchmarks Volcano 2009
OSA ISP Special Issue on Imaging for Early Lung Cancer Detection
Lung Cancer Risk
Lung Cancer Formation Significant tissue damage occurs as a result of particulate matter (PM) deposition
Hyaline Cartilage
Deposition is a function of air flow dynamics and PM characteristics Histology and CFD has shown up to a 100x greater PM deposition at: Airway bifurcations
[Broday, Aerosol Science and Tech. 2004]
Respiratory bronchioles
[Churg & Brauer, Ultrastructural Path. 2000]
Bifurcation and peripheral lung tissues likely exhibit some of the earliest preneoplastic changes in response to PM exposure
Balashazy et al., J Appl Physiol 2003.
Bifurcation Calcification in HRCT
Bifurcation Calcification Open Image Archive
1.25mm Slice Thickness w/ Bone K
Lung Cancer Risk Index (LCRI)
Features1. Bifurcation Damage Index (BDI) HRCT w/ B60f edge enhancing kernel Mean of 5 airway bifurcations(~20min)
2. FEV1/FVC Decline associated with lung cancer risk Follow ATS spirometry guidelines
BD
CD
ClassifierMethod is Independent of Age, Gender, Pack Years
Linear
BDI vs. FEV1/FVCHi gh er
Hi gh er
Regression line is for cancer cases scanned at 1mm slice thickness and FEV1/FVC > 55%
Lo w er
Lo we r
Initial Performance AnalysisDataset Conditional Logistic Regression Cochran-Mantel-Haenszel(Odds ratio for a 0.033 in LCRI with (crude estimate) 1:3 matching )
108 Cases Full Dataset
OR = 1.84 CI: 1.18-2.85 p-value = 0.0067 OR = 2.89 CI: 1.02-8.19 p-value = 0.0467
67% sensitive 72% specific
79 Cases 1mm Only
100% sensitive 74% specific
Conclusion: Individuals with higher LCRI are more likely to have lung cancer
Data on 21 Cancers and 121 ControlsCOPDPr ox im al
Di st al
Lu ng
COPD
Ca nc er
Lung Cancer Risk Findings Investigating a new quantitative imaging biomarker Airway bifurcations are calcifying in a relationship with FEV1/FVC In control cases, a significant trend observed between LCRI and age*pack years (P = 0.006) Odds Ratio for LCRI is better than FEV1/FVC LCRI = 2.73 (CI: 1.35-5.51, P = 0.005) = 0.44 (CI: 0.24-0.83, P = 0.005)
FEV1/FVC
Opportunities exist to identify new lung cancer patient sub-populations
Give-A-Scan Patient Donated Dataset Never Smoker, Cancer at 62, FEV1/FVC=84%
Right
2.5mm Scan Standard Kernel
Left
Measuring ProgressInterim Meetings
7 Workshops since 2004 1 Interim COPD Meeting Annual Workshop PCF/Cornell Database NCIA Give-A-Scan COPDGene? Large Open Image Databases
QIBA FDA NIST Standards & FDA Approval
Reproducibil ity & Comparison Early Clinical Trials BioChange & Volcano QIBA Studies
Accelerate Developme nt of Therapy Assessmen t Methods
Algorithms & Reference Methods Open Source Lesion Sizing Toolkit CT COPD Algorithms
Publications
Oncology Workshop Reports Quantitative CT Monograph ISP Oncology Special Issue
Thank You
Lung Cancer Risk Index Cancers and Age & PY Matched Controls (+/-10)
PY = Age =
5 64
15 51
20 59
28 51
30 57
40 48
45 58
59 60
60 69
63 54
66 64
68 57
72 68 74
75 62
92
Cancer Subjects Sorted by Increasing Pack Years A control case was permitted to be used for more than 1 cancer case
Lung Cancer Risk Index Cancers and Age & PY Matched Controls
1.0 mm CT Thickness Threshold
1.25 mm CT Thickness Threshold
PY = Age =
5 64
15 51
20 59
28 51
30 57
40 48
45 58
59 60
60 69
63 54
66 64
68 57
72 68 74
75 62
92
Cancer Subjects Sorted by Increasing Pack Years A control case was permitted to be used for more than 1 cancer case
(We are now using FEV1/FVC before bronchodilator)
New Study Results
(We are now using FEV1/FVC before bronchodilator)Thymom a
New Study Results
Carcinoid of the Thymus
AAH