2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Agenda
Functional imaging for RT
planning:
Normal tissue and tumor
Functional imaging vs. incorporating functional
info into CT-based planning
Normal tissue and Tumor
Interpret functional data = f (anatomy
knowledge)
Shortcomings of nuclear medicine images
PET (tumor), SPECT (normal tissues), MRI
(both)
Functional imaging: study RT-induced regional
injury
3D based planning via functional data
Functional imaging changes DURING Tx?
Helps plan tx?
Larry Marks, M.D.
Shiva Das, Ph.D.
Duke University Medical Center
Duke University
Anatomy
Function
Anatomy
Duke University
L. Marks/jh
Function
Duke University
1
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Anatomy
Tubules that
go deeper into
the medullary
portion of the
kidney do
MORE urine
concentrating
Function
•CTCT-based planning
•Actually pretty good!
•Physiologic understanding
•Better!
Duke University
anatomy/case4/4_2.html
Duke
Marks IJROBP 34:1168,
1996 University
L. Marks/jh
Marks IJROBP 34:1168, 1996
2
Duke University
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
IOF: inferior occifitofrontal fascicle
UF: uncinate fascicle
AR: acoustic radiation
MGB: medial geniculate body
LGB: lateral geniculate body
OR: optic radiation
a, c, e: optic radiation
Burgel U, et al. Neuroimage 1999; 489-499.
Duke University
3D dose
distribution
Incorporating
anatomic/functional
information to improve
CT-based planning:
Esophagus
Duke University
L. Marks/jh
University
b, d,Duke
f: lateral
geniculate body
Burgel U, et al. Neuroimage 1999; 489-499.
DVH
Outcome
(symptom)
Duke University
3
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
3D dose
distribution
DVH
Outcome
(symptom)
Anatomy
Physiology
Spatial information
Esophagus contours:
variable area
(volume)
Anatomically
Correct DVH
Duke University
Superior
Duke University
Inferior
Univariate and Multivariate Analyses
CT
esophageal
contours
3D metrics
correction
“corrected”
corrected”
3D metrics
Duke University
L. Marks/jh
Outcome
RTOG acute
& late toxicity
Duke University
4
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Toxicity = f (Dosimetric
(Dosimetric Parameters)
p-values
V 50
Uncorrected
Acute ≥ grade 2 0.008
V 50
Corrected
0.005
Acute ≥ grade 3
0.05
0.003
Late ≥ grade 1
0.14
0.08
CT + Anatomy,
physiology
>
CT alone
Adapted from Kahn et al. 2004 (Duke)
Duke University
Duke University
CT isn’
isn’t perfect.
Functional often better.
Functional Imaging
• Lung: SPECT perfusion
• Limit dose to “good”
good” lung
• Study regional normal tissue injury
• Heart: SPECT; normal tissue injury
• Tumor: PET
• Functional DVH: DF(function)H
• Plan evaluation/ranking
Duke University
L. Marks/jh
Duke University
5
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Using functional imaging to
study normal tissue toxicity
APPA
Obliques
Local dose →
local perfusion loss
SPECT perfusion
(micro(micro-emboli)
Local effects → global functional
changes
APPA
pulmonary function
tests, symptoms
Obliques
Duke University
Duke University
Prospective Study of RTInduced Lung injury
• >300 patients enrolled since 1992; 87%
white, 45% male, 70% lung primary
• PrePre- and serial postpost-RT evaluations
• Function: Pulmonary function tests (PFTs
(PFTs))
• Imaging: SPECT perfusion scan, CT scan
• Endpoints
• Symptoms, radiographs, PFTs
Duke University
L. Marks/jh
Duke University
6
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
%
Reduction
Regional
Perfusion
100
80
60
40
20
0
0
PERCENT REDUCTION
IN PERFUSION
100
75
1.5 MONTHS
9 MONTHS
3 MONTHS
12 MONTHS
6 MONTHS
50
25
0
-25
0
2000
4000
20 40 60 80 100
8000
Marks 1997
Regional Dose (Gy
(Gy))
%
Rd
reduction
perfusion
dose
response
dmax
Vd × Rd =
d=0
D
regional dose
%
lung
Vd
“volume”
volume”
From: Steppenwolde & Lebesque Sem Rad Oncol 11:247, 2001
differential
DVH
Sum of
predicted
regional injuries
“integral injury”
injury”
(overall response
parameter)
D
regional dose
L. Marks/jh
6000
DOSE (cGy)
7
Duke University
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Overall Group
60
y=x
40
Actual 20
Reduction
DLCO 0
(%) -20
-40
R = 0.30, p = 0.005
-60
0
10
20
30
40
50
Predicted Reduction in PFTs (%)
Duke University
Prospective HEART Study
Surgery:
Surgery: % Perfused Lung Removed vs.
vs.
% Decline in Pulmonary Function
• Patients
• 19981998-2005; 130 pts with leftleft-sided breast ca
• Age range 2626-82, median 54
• Treatment
• Photon tangents 4646-50 Gy
• Chemotherapy before RT: 64%
• Study design
Correlation Coefficient
Author (Number pts)
Julius (9)
Cordiner (18)
Pierce (45)*
Bolliger (22)
Giordaio (41)*
FEV1
0.80
0.82
0.87
0.81
0.87
DLCO
0.56
0.74
Single photon emission computed tomography
(SPECT) to assess left ventricular perfusion
• Pre & serial postpost-RT SPECT scans compared
• 90 patients with normal prepre-RT scans in
present analysis
•
*some % “segments”
segments” removed
adapted from Fan 2001
Duke University
L. Marks/jh
8
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
New Defect
Pre-RT
Pre-RT
Post-RT
Post-RT
Evens ES, et al. Seminars in Radiat Oncol 2007; 72-79.
Pre-RT
Post-RT
Duke University
Duke University
Rates of WallWall-Motion Abnormalities
With or Without Perfusion Defects
Months
postpost-RT
Duke University
L. Marks/jh
p-value
2-tailed
6
11%(6/55)
39%(12/31)
0.00
12
7%(3/44)
25%(6/24)
0.03
18
0%(0/25)
13%(2/16)
0.07
24
0%(0/14)
31%(4/13)
0.02
Marks ASTRO 2002
9
Perfusion Defects
No
Yes
Duke University
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
RT
Perfusion
changes
cardiac wall
motion
abnormalities
Functional Imaging
• Target delineation
changes in
ejection fraction,
symptoms
Volume Dependence- set-up accuracy
Duke University
Duke University
Rate of FDG-PET -defined change in GTV for NSCLC
Rate of PET-defined change
in gross target for lung
cancer
Munley (1996)*
Kiffer (1998)
Nestle (1999)
34% (12/25)
27% (4/15)
35% (12/34)
*Higher now: Availability, Experience, Comfort level,
Acceptable
Duke University
L. Marks/jh
Author/year
No. of pts
Overall changes in
GTV (%)
GTV increase
(%)
GTV decrease
(%)
Kiffer et al. 1998
15
4/15 (27)
4/15(27)
Munley et al. 1996
35
12/35 (34)
12/35 (34)
Nestle et al. 1999
34
12/34 (35)
3/34 (9)
9/34 (26)
Vanuysel et al. 2000
73
45/73 (62)
16/63 (22)
29/63 (40)
Mac Manus et al. 2001
102
38/102 (37)
22/102 (21)
16/102 (16)
Erdi et al. 2002
11
11/11 (100)
7/11 (64)
4/11 (36)
Mah et al. 2002
30
5/23 (22)
5/23 (22)
Cienik et al. 2003
6
5/6 (83)
1/6 (17)
4/6 (66)
Bradley et al. 2004
26
14/24 (58)
11/24 (46)
3/24 (12)
Deniaud-Alexandre, et al.
2005
101
45/92 (49)
24/92 (26)
21/92 (23)
Van der Wel, et al. 2005
21
14/21 (67)
3/21 (14)
11/21 (52)
Messa et al. 2005
18
10/18 (55)
7/18 (39)
3/18 (17)
Ashamalla et al. 2005
19
10/19 (52)
5/19 (26)
5/19 (26)
Grills et al. 2006
21
18/21 (86)
11/21 (52)
7/21 (33)
Gondi et al. 2007
14
10
12/14Duke
(86) University
2/14 (14)
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
PET: less inter-observer variability vs. CT
Atelectasis
CT GTV change
PET-CT GTV change
88% reduction in GTV
Magnitude of changes in CT-based GTV and PET-CT based GTV
among observers of head and neck cancer patients
University
Duke
Ashamalla H, et al. IJROBP 2007 ; 388-395. (Cornell
University)
Gondi V, et al. IJROBP 2007; 187-195. (University of Wisconsin)
PET: less inter-observer variability vs. CT:
Lung cancer GTV delineation
SUV-normalized FDG-PET
Projected onto planning CT
subcarinal LN
Hybrid FDG-PET/CT
blood vessels
CT GTV (overall
SD: 1.02 )
FDG/PET-CT GTV (overall
Definition of GTV based on different thresholds of SUV
SD: 0.42)
Steenbakkers RJ, et al. IJROBP 2006; 435-448.
( The Netherlands Cancer Instisute) Duke University
L. Marks/jh
Gondi V, et al. IJROBP 2007; 187-195.
11
Duke University
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Percentile SPECT
images (F50, F90)
Anatomic plan
The impact of incorporating functional imaging
into IMRT for NSCLC
Steering dose by PET via IMRT, Shiva Das 2003
Duke University
4DCT-derived ventilation image
Shioyama Y, et al. IJROBP 2007; in press.
• Path-length of the positron
• Challenges of registration
• assume "inherently registered to CT”
• Approximation
• Resolution
• Window & Level: magic
• Auto-segmentation of images
• They are typically not gated
• Need to know anatomy and patterns
spread. (larynx example)
Ventilation-constrained plan
4DCT
Yaremko BP, et al. IJROBP 2007; 562-571. Duke University
L. Marks/jh
Duke University
Shortcomings of Nuclear Medicine
Images
4DCT
Volume-constrained baseline plan
Functional plan
Duke University
12
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Functional Adaptive Therapy
• Adaptive vs. Functional Planning
• Functional more conducive for
adaptive??
• Function changes faster
• Animal and human data supporting
physiologic changes early during
therapy
• Physiologic changes -->
--> Outcome
• MRI and PET
Monte Carlo-calculated distribution of annihilation events
around a positron point source embedded in different tissues
as seen in the image plane of a PET camera
University
Sanchez.
Sanchez-Crespo A, et al. Eur J Nucl Med Mol Imaging 2004; 4444-51.
51Duke
Duke University
Start Therapy
Modifying therapy based
on physiologic changes
during RT
Assess Response
Not going
well
Going Well,
Continue
Alter Therapy or
Abort Therapy
Duke University
L. Marks/jh
13
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Even without variation in function
tumor
Gamma detector
patient
What may change?
• Oxygenation
• Cell cycle distribution
• Growth fraction
• Tumor growth
Align daily per
SPECT (or PET)
Gamma detector
Duke University
Duke University
Changes in P O2 in transplanted tumors in animals
Kinetics of:
Reoxygenation: Days
Experimetal models (Hall pp 106)
Humans: RT and Hyperthermia (Brizel)
Resortment: Days
Human cell Lines
Cell Cycle- specific drug efficacy
Repopulation: Days
Writher's, Fowler's Data
Human trials of shortened treatment time
Radiobiology for the Radiologist; Eric Hall, Lippincott Williams
And Wilkins, 2004, via Rockwell
Duke University
Duke University
L. Marks/jh
14
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Sample of human data supporting
physiologic changes during RT
Brizel et al
• Soft tissue sarcoma (N=21)
• Serial P O2 measurements (Eppendorf
(Eppendorf))
• PrePre-RT
• During first wk of RT; prepre-heat
• After FIRST heat treatment
• Related P O2 changes to pathologic
response
• P O2
• MRI
• PET
Cancer Research 56: 5347, 1996, Duke University
Duke University
<--- RT --->
Sarcoma
Diagnosis
<-- Heat -->
Duke University
Early changes in P O2 predict for later pathologic response
Resection:
Assess
pathologic
response
Pre- Post- PostRT RT RT/Heat
Median 6
4
12
P O2
Brizel, Cancer Research
56: 5347, 1996, Duke
University
P O2 post-first heat/pre-tx
Brizel, Cancer Research 56: 5347, 1996, Duke University
Duke University
L. Marks/jh
Duke University
15
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Meisany et al
Breast
Cancer
Diagnosis
• Invasive Breast Cancer, N = 16
• Adria and Cytoxan x 4
• T size 2-9cm
• MRI for size and spectroscopy (choline)
-Pre Chemo
-24 hrs after dose 1
-after 4th cycle
4 cycles chemo
Pre- 24
RT hours
Assess
clinical
response
Postchemo
MRI assessments
Radiology 233:424-31, 2004, University of Minnesota
Meisamy Radiology 2004
Duke University
Duke University
Time Intensity Curve of ROIs
Isodose distribution
Choline Level
(24 hrs/Pre-chemo)
ROIs
Before RT
Response rate
after 4 Cycles
<1
8/8
>1
0/5
30Gy
Before RT
After RT
tumor
At week 2 of RT
15Gy
p < 0.01
T1 contrast
enhancement MRI
spleen
Meisamy, Radiology 233:424-31, 2004
Liang PC, et al. Liver Int 2007; 516-528.
Duke University
L. Marks/jh
16
Duke University
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Outcome by “early PET”
PET” response to RT/CT
Author
Site
Interval postpost-tx
EndEnd-point
Response
Hokestra
lymph
Cycle 11-2 chemo
NED
1/1
0/1
Spaepen
lymph
After chemo
NED
56/67
0/26
Summary
No Response
•
Physiology/function with CT-based planning
• Need to understand anatomy to interpret nuclear
•
Functional imaging: Normal tissue and Tumor
• PET, SPECT, MRI
• RT-induced regional injury
Shortcomings of nuclear medicine images
• e.g. Path length, fusion
Functional imaging changes DURING Tx?
3D based planning via functional data (Shiva)
Abe
lung
End tx
CR
3/3
0/2
Bury
lung
6 mo
NED
44/44
1/14
Jerusalem
NHL
Cycle 3 chemo
NED
14/23
0/5
Greven
H/N
1 mo post chemo
NED
13/16
0/6
Weber
GE Junc
Wk 2 preop
chemo
NED (40 pts)
50%
10%
•
•
•
Patz
lung
Variable 11-12 mo
NED
11/13
9%
Ryu
lung
2 wks post RT/CT
Path CR
5/11
3/15
Choi
lung
2 wks post RT/CT
Path CR
13/17
1/13
Erdi
lung
During RT
response
1/1
0/1
medicine/functional images
Duke University
Duke University
Acknowledgments
Radiation Oncology:
Lawrence Marks, M.D.
Jessica Hubbs,
Hubbs, B.S.
Jinli Ma, M.D.
Patricia M. Hardenbergh,
Hardenbergh, M.D.
Christopher Kelsey, M.D.
Carol Hahn, M.D.
John Kirpatrick,
Kirpatrick, M.D., Ph.D.
Pulmonary: Rodney Folz
Cardiology: Michael Blazing
Data/Statistics:
Robert Clough
Donna Hollis, M.S.
Andrea Tisch,
Tisch, R.T.T.
UNC: Julian Rosenman
Varian Medical Systems, NIH CACA-69579 and
R01R01-CA33541, and DOD DAMD 1717-9898-1-
8071 and 1717-0202-1-0374, Lance Armstrong
L. Marks/jh
Radiation Physics:
Shiva Das,
Das, Ph.D.
SuSu-Min Zhou, Ph.D.
Junan Zhang, Ph.D.
FangFang-Fang Yin, Ph.D.
Michael Munley,
Munley, Ph.D.
Daniel Kahn, Ph.D.
Moyed Miften,
Miften, Ph.D.
Kim Light, R.T.T., C.M.D.
Phil Antoine
Jane Hoppenworth
Functional Image-Guidance to Reduce
Toxicity: Treatment Planning and
Technical Details
Shiva Das & Lawrence Marks
Dept of Radiation Oncology
Nuclear Medicine:
Terry Wong, M.D.
R. Edward Coleman, M.D.
Ronald Jaszczak,
Jaszczak, Ph.D.
Salvador BorgesBorges-Neto
Duke University
Duke University
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ASTRO 2003: High dose Tx for Lung Ca
Single Photon Emission Computed Tomography
SPECT provides a map of perfusion.
Asumption: all areas of normal lung have equal function.
Reality: lung function is spatially heterogeneous.
Reduce lung toxicity: reduce dose to higher functioning
better quality of life!
normal lung
In animal studies: perfusion ∝ function
Duke University
Duke University
This is all well and good, except that ECLIPSE does
not accept SPECT images …………….
Objectives
Create a CT look-alike containing SPECT data
Develop a manual algorithmic methodology for
integrating SPECT-guidance into the ECLIPSE treatment
planning optimization process.
Register SPECT to planning CT outside ECLIPSE
Resample SPECT to match CT slices and resolution
Make a copy of DICOM CT which will be used to
house SPECT data (“fake” CT)
Modify DICOM header in fake CT; strip out CT Data
and replace with SPECT data
Import fake CT (SPECT data) into ECLIPSE.
Automate the methodology.
Apply in clinic!
Duke University
L. Marks/jh
Duke University
18
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Methodology
Initial IMRT plan generated without SPECT-guidance.
Dose-volumes obtained in this plan are used in SPECTguided plan.
SPECT image is segmented into 4 areas from low to high
intensity.
Duke University
Duke University
Methodology (cont’d.)
Functional Metrics
Set current SPECT structure under consideration to the
lowest intensity structure.
VD = volume above D Gy.
For all SPECT structures with higher intensity, volumes
above constraint doses are constrained to zero (maximum
importance).
FD = function above D Gy (function = volume × SPECT
intensity)
Optimize PTV dose while keeping all normal structures
other than lung within dose-volume limits.
DVH: Dose volume histogram.
If PTV coverage is unsatisfactory, or normal structures
other than lung have exceeded limits, set the SPECT
structure under consideration to the next higher intensity
structure, and repeat.
DFH: Dose function histogram.
Duke University
L. Marks/jh
Duke University
19
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Patients
Manually implemented this methodology in 5 lung cancer
patients.
9 beams oriented at 30° spacing on predominant tumor
side.
SPECT distribution can be
very spatially heterogeneous
Primary tumor to 40 Gy, boost to 66 Gy.
Duke University
Duke University
Dose Function Histograms: SPECT Structures
(one patient)
Base Plan
SPECT Plan
4
15
10
60
SPECT
0
0
20
5
40
Dose (Gy)
60
0
0
80
Highest intensity SPECT region DFH
0
0
20
40
Dose (Gy)
60
Base
80
40
40
Dose (Gy)
60
80
20
10
40
Dose (Gy)
60
80
0
0
20
40
Dose (Gy)
100
Base Plan
SPECT Plan
80
Base Plan
SPECT Plan
80
Lowest SPECT
intensity structure
20
Lung DFH
% Function
Lung DFH
% Function
3rd Highest SPECT
intensity structure
30
% Function
% Function
Base Plan
SPECT Plan
15
40
20
0
0
100
40
Base Plan
SPECT Plan
20
60
2nd Highest intensity SPECT region
DFH
30
25
Lung DFH
60
20
SPECT
20
Base Plan
SPECT Plan
80
Lung DFH
40
20
2
100
Base Plan
SPECT Plan
80
Lung DFH
% Function
% Function
6
100
Base Plan
SPECT Plan
80
2nd Highest SPECT
intensity structure
% Function
20
Highest SPECT
intensity structure
Base
% Function
100
25
Base Plan
SPECT Plan
8
% Function
10
Lung Dose-Function Histograms (5 patients)
60
40
20
60
40
20
10
0
0
5
0
0
20
40
Dose (Gy)
60
80
0
0
20
40
Dose (Gy)
60
40
Dose (Gy)
60
80
0
0
80
Duke UniversityLowest intensity SPECT region DFH
3rd Highest intensity SPECT region
DFH
L. Marks/jh
20
Duke University
20
20
40
Dose (Gy)
60
80
60
80
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Dose distribution
Lung function sparing above 20 Gy, 30 Gy
Patient
F20
Base
(%)
% Reduction
Base
(%)
SPECT
(%)
%
Reduction
15.6
A
60.6
51.0
15.8
37.9
32.0
B
56.3
51.1
9.2
37.2
35.1
5.6
C
52.0
44.6
14.2
29.0
27.3
5.9
18.0
D
17.2
13.6
20.9
8.9
7.3
E
46.1
42.4
8.0
26.5
24.5
Average
Non SPECT-guided plan
F30
SPECT
(%)
13.6 ± 5.2
SPECT-guided plan
Duke University
Average
7.5
10.5 ±
5.8
Duke University
Clinical Case
Clinical Application
58 yo male
Clinician
Physics
SPECT/PET facility
Lawrence Marks, MD
Shiva Das, PhD
Tim Turkington, PhD
(SPECT – NIH funded)
Sarah McGuire, PhD
Terry Wong, MD
poor pulmonary function: FEV1 0.7 liters 20% predicted
Sumin Zhou, PhD
solitary nodule (non-small cell)
2.5 cm in medial rt central lung
hypermetabolic on PET
Patient imaged in CT-SPECT (GE Hawkeye system)
Duke University
L. Marks/jh
Duke University
21
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
GE HAWKEYE SYSTEM
Clinical Case
Planning CT
CT from SPECT
Patient imaged with 4D CT
ITV created from union of 4DCT GTVs
Expanded to create PTV: 1 cm margin; 1.5 cm in sup-inf
Patient imaged in CT-SPECT (GE Hawkeye system)
CT from SPECT – poor quality (maybe not
suitable for dose computation?)
Nevertheless, very useful for registration
Prescription: SBRT 12 Gy × 4 fractions
Planning CT
CT from SPECT
Duke University
Duke University
SPECT
GE HAWKEYE SYSTEM
Converting SPECT to TPS readable DICOM
Integrates GE Millennium VG SPECT with low power X-ray tube and
detector array.
CT: 256 × 256 × 40
X-ray generator: 2.5 mA, 140 kVp
0.22 cm pixel size
CT: 10 mm thick slices, 256 x 256,
∼1.5 mm inplane resolution.
SPECT: 128 × 128 × 128
40 slices, acquired at 3 slices/minute.
0.44 cm pixel size
SPECT: continuous rotation or stepand-shoot mode.
CT: 40 cm
(1cm spacing)
SPECT and CT can not be acquired
simultaneously.
SPECT: 57 cm
(0.44 cm spacing)
Duke University
L. Marks/jh
Duke University
22
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Converting SPECT to TPS readable DICOM
SPECT: obtained as interfile format (nuclear medicine format) from
GE Hawkeye system
Converting SPECT to TPS readable DICOM
Resample SPECT into space of CT image
128 × 128 × 128 → 256 × 256 × 40 (unsigned int*16)
CT: dicom format
Interfile Format
2 files: .img and .hdr
Can be read using MATLAB interfileinfo(), interfileread()
Info
TotalNumberOfImages (number of slices)
CentreCentreSliceSeparationPixels (slice separation in pixels)
MatrixSize (resolution)
SPECT dicom: replace CT dicom data with resampled SPECT data.
To prevent confusion, change StudyInstanceUID and
SeriesInstanceUID in SPECT dicom. e.g., change list digits of both:
StudyInstanceUID =
1.2.124.113532.152.16.194.14.20070430.84447.6023314,
SeriesInstanceUID =
1.2.840.113619.2.170.1.2.0.152007.152731390.30842
ScalingFactorMmPixel (pixel
size)
Duke University
Duke University
Optimization Strategy (original)
Optimization Strategy (simpler)
Title: A methodology for using SPECT to reduce intensity-modulated radiation therapy (IMRT)
dose to functioning lung
Author(s): McGuire SM (McGuire, Sarah M.), Zhou SM (Zhou, Sumin), Marks LB (Marks,
Lawrence B.), Dewhirst M (Dewhirst, Mark), Yin FF (Yin, Fang-Fang), Das SK (Das, Shiva K.)
UniversityONCOLOGY BIOLOGY PHYSICS 66 (5):
Source: INTERNATIONAL JOURNAL OFDuke
RADIATION
1543-1552 DEC 1 2006
L. Marks/jh
Duke University
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2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
BEAM DIRECTION SELECTION IS IMPORTANT FOR SPECT AVOIDANCE
Highest SPECT activity region
Duke University
Duke University
2 Highest SPECT activity regions
3 Highest SPECT activity regions
Duke University
L. Marks/jh
Duke University
24
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Dose Distribution
4 Highest SPECT activity regions
Duke University
Duke University
PTV and Highest SPECT region DVHs
2nd Highest SPECT region DVH
PTV “conventional” plan
PTV SPECT-guided plan
“conventional” plan
“conventional” plan
SPECT-guided plan
SPECT-guided plan
Duke University
L. Marks/jh
Duke University
25
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
4th Highest SPECT region DVH
3rd Highest SPECT region DVH
“conventional” plan
“conventional” plan
SPECT-guided plan
SPECT-guided plan
Duke University
Duke University
DVH of remaining minimally perfused lung
DVH of all lung
“conventional” plan
“conventional” plan
SPECT-guided plan
SPECT-guided plan
Duke University
L. Marks/jh
Duke University
26
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
SPECT-guided vs. Conventional Plan: mean dose in
SPECT regions (Patient #2)
SPECT-guided vs. Conventional Plan: mean dose in
SPECT regions
Dose: 33 fxs × 200 cGy
Overall mean lung dose reduction: 3.2 vs. 3.7 Gy (13% ↓)
Overall mean lung dose reduction: 7.9 vs. 8.3 Gy (6% ↓)
1st Highest SPECT region: 1.2 Gy vs. 2.4 Gy (49%↓
↓)
2nd Highest SPECT region: 4.6 Gy vs. 6.7 Gy (32% ↓)
1st Highest SPECT region: 6.4 Gy vs. 7.2 Gy (12%↓
↓)
3rd Highest SPECT region: 3.4 Gy vs. 4.1 Gy (17% ↓)
2nd Highest SPECT region: 8.0 Gy vs. 8.8 Gy (8% ↓)
4th Highest SPECT region: 2.1 Gy vs. 2.4 Gy (13% ↓)
3rd Highest SPECT region: 8.5 Gy vs. 8.8 Gy (4% ↓)
Remaining “non-perfused”: 3.45 vs. 3.42 Gy (1%↑
↑)
4th Highest SPECT region: 7.1 Gy vs. 7.3 Gy (3% ↓)
Remaining “non-perfused”: 9.1 vs. 9.0 Gy (1%↑
↑)
Patient was treated with Amplitude Gating and CBCTDuke University
guided setup
Duke University
ONE THOUGHT TO LEAVE YOU WITH ….
In addition to using SPECT avoidance,
Put higher tumor dose in FDG-PET avid areas, or,
dump “collateral” high dose into FDG-PET avid areas.
CONCLUSION
Incorporating SPECT-guidance into IMRT planning
for thoracic tumors reduces irradiated functioning
(hopefully) reduced toxicity.
lung volumes
Controversial, but ….
Several studies have shown that higher FDG-uptake is
correlated to higher grade and poorer response posttherapy.
Perhaps more appropriate for proliferation (18F-FLT)
or hypoxia (18F-MISO). Duke University
Duke University
L. Marks/jh
27
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
sagittal
axial
Local effect
Local dose
Patients don’
don’t usually care about
imaging!
3D RT dose
∆ PFT
Sum local effects
Functional
imaging SPECT
coronal
Title: Feasibility of optimizing the dose distribution in lung tumors using fluorine-18fluorodeoxyglucose positron emission tomography and single photon emission
computed tomography guided dose prescriptions
Author(s): Das SK, Miften MM, Zhou S, Bell M, Munley MT, Whiddon CS, Craciunescu O,
Duke University
Baydush AH, Wong T, Rosenman
JG, Dewhirst MW, Marks LB
Source: MEDICAL PHYSICS 31 (6): 1452-1461 JUN 2004
Duke University
Correlation Coefficient (R): Predicted
vs.
vs. Measured Decline in DLCO
Predicting Changes in PFT’s
Dmax
∑ [(fraction lung at dose i) ×
i=0
(effect at dose i)] = total loss
96 patients with followfollow-up
PFT’
PFT’s ≥ 6 months
Fan et al. JCO and IJROBP 2001
L. Marks/jh
Symptoms
No “Central
Tumor With
Adjacent
Hypoperfusion”
Hypoperfusion”
# FU
PFT’
PFT’s
All
Patients
≥1
0.41 (59)
0.40 (28)
≥2
≥3
0.40 (43)
0.56 (17)
0.60 (22)
0.91 (8)
Fan 2001
Duke University
Duke University
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ASTRO 2003: High dose Tx for Lung Ca
Duke University
Duke University
Physiologic Imaging in Oncology
• ChemoChemo-, radioradio-, and heat therapy
•MRI, MRS, PET, etc
Treatment
Planning
PET-based GTV
Subcarinal area
Normal
Tissue
Effects
Tumor
Imaging
Extent
e.g. Hypoxia
adjust
Esophagus
Assess
Tumor
Response
• optimize therapeutic ratio in each patient
Duke University
L. Marks/jh
PlanUNC software, Courtesy UNC
29
Duke University
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
Automatic
image
segmentation
of targets
PET-based GTV
Subcarinal area
PlanUNC software, Courtesy UNC
Lymph node
Greco C, et al. Lung Cancer 2007 ; in press.
(University of Magna Graecia, Italy)
Duke University
Duke University
Oropharyngeal cancer
Base-of– tongue cancer
Esophageal cancer
PET-CT (blue)
CT-GTV (blue)
Floor-of-mouth cancer
PET-CT (blue)
CT-GTV (red)
CT-GTV (red)
GTV
Floor-of-mouth cancer
Nasopharyngeal cancer
CT-GTV (yellow)
CT-GTV (blue)
PET-CT (green)
PET-CT (green)
PET-CT GTV (purple)
Leong T, et al. Radiother Oncol 2006; 254-261.Duke University
(University of Melbourne, Australia)
L. Marks/jh
Duke
University
Ashamalla H, et al. IJROBP 2007 ; 388-395. (Cornell
University)
30
2007-8-16
ASTRO 2003: High dose Tx for Lung Ca
CT vs PET-weighted EUD
(a): transverse slice
(b): sagittal slice
(c): coronal slice
Isodose lines (Gy) superimposed on slice
planes through FDG-PET
Dose painting- IMRT
Das SK, et al. Med Phys 2004; 1452-1461.
Duke University
Das SK, et al. Med Phys 2004; 1452-1461.
Responders
MRIbased
change
early
during
Tx
Non-responders
Percent change lesion diameter end of therapy
Radiology; Meisamy et al., Nov, 2004
Radiology; Meisamy et al., Nov, 2004
Duke University
L. Marks/jh
Duke University
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ASTRO 2003: High dose Tx for Lung Ca
Development of Motion Envelope
Projection of 4DCT GTVs onto PET
motion-induced smear
(a) Non-gated acquisition
(b) 4DCT/PET gated acquisition
Fusion of 4DCT with FDG-PET
Nehmeh SA, et al. Med Phys 2004; 3179-3186.
Duke University
Duke University
Gondi V, et al. IJROBP 2007; 187-195.
Monitoring response to Tx with functional
imaging during RT
Study
Distribution of
percentile functional
Lung volume
(4DCT ventilation images)
Tx
Tumor Test Follow-up
Findings
19 SRS
Brain
PET
4 h after SRS
↑ FDG uptake →↓ tumor size
Harvey
2001
22 RT
Prostate
CT
1-2 weeks, 612 weeks
↑blood flow during Tx
Wieder
2004
38 Chem Esophagus PET
RT
2 weeks after
initiation
of Tx
↓SUV→↑
→↑tumor
response and
→↑
survival
early identification of non-responders
and early modifications of Tx
protocol
Tsien
2007
20 RT
Glioma
MRI
During weeks
1 and 3 of
RT
T1 weighted signal intensity changes
→ predictive of overall survival
Liang
2007
19 RT
HCC
DCEMRI
At 2 weeks of
Tx
↑Initial first-pass enhancement
slopes (slope) and peak
enhancement ratios (peak)
→↑local
response
→↑ Duke
University
Duke University
Yaremko BP, et al. IJROBP 2007; 562-571. Duke University
L. Marks/jh
n
Maruyama
1999
32
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ASTRO 2003: High dose Tx for Lung Ca
IMRT Case: Target Outlines
CT
FDG-PET
PET Avid
Regions
PET-GTV
CT-GTV
BEV
SPECT
High Perfusion
CT-GTV
PET-GTV
Low Perfusion
Duke University
L. Marks/jh
33