ACRIN Abdominal Committee ACRIN Gynecologic Committee Fall Meeting 2010

ACRIN Abdominal Committee

ACRIN Gynecologic Committee


Fall Meeting 2010



CT Perfusion Study of Ovarian Cancer

ACRIN 6695 Project Team


Study Schedule

Cycle 1 (All cycles 3 weeks in length)

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

Ovarian cancer:

suboptimallydebulked

(e.g. > 1 cm tumor

left behind Surgically)

Cycle 1 (All cycles 3 weeks in length)

Baseline RECIST CT scan & Perfusion CT Baseline (T0)

At least 3 weeks post surgery and within 4 weeks prior to

initiating protocol chemotherapy

Carboplatin AUC 6 IV day 1 every cycle x 6 cycles

Regimen I:

Regimen II:

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

RANDOMIZE

Follow-up RECIST CT scansafter 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

Perfusion CT (T2)After one week into cycle 2

Cycle 2

Perfusion CT intermediate (T1)

at end of 1st cycle between 18-21 days

Reproducibility Perfusion CT

A subgroup of patients will be studied

Paclitaxel 175 mg/m2 IV Day 1 every cycle x 6 cycles

Cycle 3 Cycle 4 Cycle 5 Cycle 6

Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6

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


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 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

CT Perfusion Study Protocol


64-slice CT scanner with 40 mm wide detector array without toggling table mode

CT Perfusion Scan Protocol

Inject 300 – 370 mgI/ml contrast

0.8 ml/kg @ 3 – 4 ml/s

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 12 114 117 120s

1 2 3 4 38 39 40

Effective Dose = 7.2 mSvSkin dose = 150 mGy


64-slice CT scanner with 40 mm wide detector array with toggling table mode



0.8 ml/kg @ 3 – 4 ml/s

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 12 114 117 120s

1 2 3 4 38 39 40



128-slice CT scanner with 80 mm wide detector array



0.8 ml/kg @ 3 – 4 ml/s

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 12 114 117 120s

1 2 3 4 38 39 40






0.8 ml/kg @ 3 – 4 ml/s



0s 3 6 9 12 114 117 120s

1 2 3 4 38 39 40






0.8 ml/kg @ 3 – 4 ml/s



0s 3 6 9 12 114 117 120s

1 2 3 4 38 39 40



Example CT Perfusion Scan of Prostate

Intravenous Injection of

Contrast Agent

60-70 ml @ 3-4 ml/s

Scan ProtocolEach scan: 16 x 5 mm slices @

80 kVp and 50 mAs1 scan every 2.8 s

42 scans

Deco

nvo

lutio

n w

ith p

hysio

l mo

del

Effective dose 21 mSv

-5

0

5

10

15

20

25

30

35

40

0 20 40 60 80 100 120 140

Time (s)

En

han

cem

ent

(HU

)

Artery

0

50

100

150

200

250

0 20 40 60 80 100 120 140

Time (s)

En

han

cem

ent

(HU

)

Average

Blood Volume

Blood Flow

PS

AVG

BF

BV

PS


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

Primary Objective


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 every-3-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, user-independent and reproducible parameters of tumor microvascular characteristics. A subgroup of 15 patients will have repeat CT Perfusion studies at T1 to achieve this objective

Secondary Objectives


Radiation Dose Effective dose

• Research plus normal care – 87.2 mSv• Annual background – 3.0 mSv

Cancer induction and fatality risk BEIR VII report

• Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, National Research Council

Radiation Risk

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



Questions ?

Documents

ACRIN Abdominal Committee ACRIN Gynecologic Committee Fall Meeting 2010