ACRIN Gynecologic
Committee
Fall Meeting 2010
ACRIN Abdominal Committee
ACRIN Gynecologic Committee
CT Perfusion Study of
Ovarian Cancer
ACRIN 6695 Project Team
ACRIN Abdominal Committee
ACRIN Gynecologic Committee
Study Schedule
Regimen I:
Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6
Cycle 1 (All cycles 3 weeks in length)
Ovarian
cancer:
suboptimally
debulked
(e.g. > 1 cm
tumor
left behind
Surgically)
R
A
N
D
O
M
I
Z
E
Carboplatin AUC 6 IV day 1 every cycle x 6 cycles
Paclitaxel 175 mg/m2 IV Day 1 every cycle x 6 cycles
Bevacizumab 15 mg/kg IV day 1 every cycle
starting cycle 2 and continuing beyond cycle 6
until progression or adverse effects preclude
further treatment
Regimen II:
Cycle 1 (All cycles 3 weeks in length)
Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6
Carboplatin AUC 6 IV day 1 every cycle x 6 cycles
Paclitaxel 80 mg/m2 IV days 1, 8 and 15 every cycle x 6 cycles
Bevacizumab 15 mg/kg IV day 1 every cycle
starting cycle 2 and continuing beyond cycle 6
until progression or adverse effects preclude
further treatment
Perfusion CT
intermediate (T1)
Baseline RECIST CT scan &
Perfusion CT Baseline (T0)
at end of 1st cycle between 18-21 days
At least 3 weeks post surgery
and within 4 weeks prior to
initiating protocol chemotherapy
Perfusion CT (T2)
Reproducibility
Perfusion CT
After one week into cycle 2
A subgroup of patients will be studied
ACRIN Gynecologic Committee
Follow-up RECIST CT scans
after cycle 3,6,14,22
After completion of all protocol therapy,
every 3 months for 2 years,
then every 6 months for 3 years, then annually
CT Perfusion Study Protocol
 Scout to define limits of localization scan
 Localization scan
 Use site abdominal scan protocol
 Define limits of tumor, either 4 or 8 cm slab
 If follow-up study, try locate the same tumor slices as the initial baseline study
 CT Perfusion scan as per protocol
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GE Healthcare scanner - non axial shuttle mode
GE Healthcare scanner – axial shuttle mode
Toshiba Aquilion One scanner
No breath-hold, patient is instructed to breath normally during scan
 Contrast dose
 0.7 ml per kg body weight up to a max of 65 ml
 Injection rate 3-4 ml per second
 Radiation dose
 4 cm coverage : 9.5 mSv
 8 cm coverage : 16.8 mSV
ACRIN Gynecologic Committee
CT Perfusion Scan Protocol
 64-slice CT scanner with 40 mm wide detector array
without toggling table mode
40 axial scans @ 2.8 - 3 s intervals:
120 kVp; 100 mA; 8 x 5 mm slices;
0.4 s rotation period
0s
3
6
9
12
1
2
3
4
Inject 300 – 370
mgI/ml contrast
0.8 ml/kg @ 3 – 4 ml/s
ACRIN Gynecologic Committee
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114
117
120s
38
39
40
Effective Dose = 7.2 mSv
Skin dose = 150 mGy
CT Perfusion Scan Protocol
 64-slice CT scanner with 40 mm wide detector array
with toggling table mode
40 passes @ 2.8 - 3 s intervals:
120 kVp; 100 mA; 16 x 5 mm
slices; 0.4 s rotation period
0s
3
6
9
12
1
2
3
4
Inject 300 – 370
mgI/ml contrast
0.8 ml/kg @ 3 – 4 ml/s
ACRIN Gynecologic Committee
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114
117
120s
38
39
40
Effective Dose = 14.3 mSv
Skin dose = 150 mGy
CT Perfusion Scan Protocol
 128-slice CT scanner with 80 mm wide detector array
40 axial scans @ 2.8 - 3 s intervals:
120 kVp; 100 mA; 16 x 5 mm slices;
0.4 s rotation period
0s
3
6
9
12
1
2
3
4
Inject 300 – 370
mgI/ml contrast
0.8 ml/kg @ 3 – 4 ml/s
ACRIN Gynecologic Committee
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114
117
120s
38
39
40
Effective Dose = 14.3 mSv
Skin dose = 150 mGy
CT Perfusion Scan Protocol
 256-slice CT scanner with 120 mm wide detector
array
40 axial scans @ 2.8 - 3 s intervals:
120 kVp; 100 mA; 20 x 5 mm slices;
0.4 s rotation period
0s
3
6
9
12
1
2
3
4
Inject 300 – 370
mgI/ml contrast
0.8 ml/kg @ 3 – 4 ml/s
ACRIN Gynecologic Committee
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114
117
120s
38
39
40
Effective Dose = 17.8 mSv
Skin dose = 150 mGy
CT Perfusion Scan Protocol
 320-slice CT scanner with 160 mm wide detector
array
40 axial scans @ 2.8 - 3 s intervals:
120 kVp; 100 mA; 24 x 5 mm slices;
0.4 s rotation period
0s
3
6
9
12
1
2
3
4
Inject 300 – 370
mgI/ml contrast
0.8 ml/kg @ 3 – 4 ml/s
ACRIN Gynecologic Committee
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114
117
120s
38
39
40
Effective Dose = 21.4 mSv
Skin dose = 150 mGy
Example CT Perfusion Scan of Prostate
Average
Effective dose 21 mSv
Enhancement (HU)
200
150
Artery
100
50
0
0
20
40
60
80
100
120
140
Time (s)
Scan Protocol
Each scan: 16 x 5 mm slices @
80 kVp and 50 mAs
1 scan every 2.8 s
42 scans
40
35
30
Enhancement (HU)
Intravenous
Injection of
Contrast
Agent
60-70 ml @
3-4 ml/s
25
20
15
10
5
0
0
ACRIN Gynecologic Committee
20
40
60
80
-5
Time (s)
100
120
140
Deconvolution with physiol model
250
AVG
Blood Flow
BF
Blood Volume
BV
PS
PS
Primary Objective
 To determine whether larger changes in the tumor
perfusion parameters (BF, BV, MTT, PS) from
baseline T0 to T2 are predictive of higher
progression-free survival (PFS) rate at 6 months in
patients treated with weekly paclitaxel regimen or
every-3-week paclitaxel regimen, who are receiving
carboplatin with or without bevacizumab
ACRIN Gynecologic Committee
Secondary Objectives
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To determine whether larger changes in tumor perfusion parameters from
baseline T0 to T1 are predictive of higher progression-free survival (PFS)
rate at 6 months in patients treated with weekly paclitaxel regimen or every3-week paclitaxel regimen, who are receiving carboplatin with or without
bevacizumab
To determine whether larger changes in tumor perfusion parameters values
from T0 to T1, T0 to T2 and T1 to T2 are predictive of better overall survival
in all treatment arms.
To assess the association between changes in tumor perfusion parameters
before and after chemotherapy and subsequent best tumor response
according to standard anatomic response evaluation criteria (RECIST).
To assess the association between tumor perfusion parameters before
chemotherapy and subsequent best tumor response according to standard
anatomic response evaluation criteria (RECIST), progression free survival at
6 months and overall survival.
To test the assumption that tumor perfusion parameters are reliable, userindependent and reproducible parameters of tumor microvascular
characteristics. A subgroup of 15 patients will have repeat CT Perfusion
studies at T1 to achieve this objective
ACRIN Gynecologic Committee
Radiation Risk

Radiation Dose
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Effective dose
•
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Research plus normal care – 87.2 mSv
Annual background – 3.0 mSv
Cancer induction and fatality risk
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BEIR VII report
•
Committee to Assess Health Risks from Exposure to Low Levels of Ionizing
Radiation, National Research Council
Excess cases of cancer (all solid cancers and leukemia including
non-fatal cases) from ONE DCE-CT study per 100,000 exposed
1,195
Number of cancer cases per 100,000 in the general population
not exposed to radiation
37,490
Excess cases of cancer death from ONE CT Perfusion study per
100,000 exposed
576
Number of cancer deaths per 100,000 in the general population
not exposed to radiation
18,030
ACRIN Gynecologic Committee
Questions ?
ACRIN Abdominal Committee
ACRIN Gynecologic Committee