response evaluation of gastrointestinal stromal tumors (gist) haesun choi, m.d. diagnostic imaging...
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Response Evaluation of Gastrointestinal Stromal Tumors
(GIST)
Haesun Choi, M.D.Diagnostic Imaging
The University of Texas MD Anderson Cancer Center, Houston, TX
Gastrointestinal Stromal Tumor(GIST)
Imatinib mesylate
Tyrosine kinase receptor blocker
+
Kinasedomains
“KIT” receptor
Chris Corless, M.D.
““Computed Tomography (CT) and Magnetic Computed Tomography (CT) and Magnetic
Resonance Imaging (MRI) are the best currentlyResonance Imaging (MRI) are the best currently
available and most reproducible methods for available and most reproducible methods for
measuring the target lesions …”measuring the target lesions …”
Thessasse et al. JNCI 92(3); 205, 2000
Fluorine-18-fluorodeoxyglucose
Positron Emission Tomography (FDG PET)
8/9/02 10/28/02
Pre-Treatment Pre-Treatment
Computed Tomography
(CT)
Gastric GIST Metastatic GIST
Small bowel GIST Metastatic GIST
6/01HU 633.3 cm
8/01HU 382.3 cm
10/01HU 321.9 cm
2 Months PostPre-Treatment
5 Days PostPre-Treatment
Pre-Treatment 2 Months Post
43 HU 30 HU
Methods and Materials (I)
• Total patients = 36 CT* and PET* = 29
*within a week of each other
• Total lesions = 173
Liver: 116
Peritoneum: 52
Pleura: 5
• CT vs. PETCT vs. PET
PET: EORTC1999PET: EORTC1999
Tumor size Tumor size (cm)(cm)
Tumor density Tumor density (HU)(HU)
““Overall Overall tumor tumor status status (OTS)”(OTS)”
Subjective Tumor Response Evaluation: OTS
Pre-Treatment
tumor vessels
solid tumor
nodules
tumor density
Size +
2 Months PostPre-Treatment
Pre-treatment
8 Wks Post-treatment
0
2
4
6
8
10
0
20
40
60
80
100
Size Mean HU
0
2
4
6
8
10
Mean SUVmax
P = 0.0025, t-test P<0.0025, t-test
P = 0.0025, t-test
Objective Tumor Response Evaluation
Size vs. SUV
No. Patients
by Changes in SUVmax**
No. of Patients by Changes in Size*Total
No. of
PatientsPD SD PR CR
Grade 1 0 2 0 0 2
Grade 2 1 5 0 0 6
Grade 3 0 1 0 0 1
Grade 4 1 15 4 0 20
Note. - The data were analyzed for the 29 patients who underwent both CT and FDG PET. * Based on RECIST ** Based on modified EORTC 1999 criteria
Methods and Data Analysis (II)
• Total patients = 40
CT and PET
• “Good Response”:Decrease in SUVmax
>70% <2.5
• Good Response: 33 (83%)– 30 (75%): PET CR
– 3 (8%): 70 - 99% decrease, decrease to a value <2.5
• Poor Response:7 (17%)– 5 (12%): stable
– 2 (5%): increased SUVmax
(Van den Abbeele AD, et al, ASCO 2002)
Changes in Size and HU on CT vs. Tumor Response on FDG PET
Tumor response by PET
Patients with
10% decrease in size
(%)
Patients with
15% decrease in HU (%)
10% decrease in size or 15%
decrease in HU (%)
Good
(n=33)31 (94) 27 (82) 32 (97)
Poor
(n=7)0 (0) 0 (0) 0 (0)
n – number of patients
Total number of patients = 40
Modified CT Criteria
+++ ++ ++ ++ ++++++++++ +++++++++++++++
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302724211815129630
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Non-responderResponder Responder
P = 0.03P = 0.03
PET response:
SUV < 2.5, 70%
CT response:
HU -15%, Size -10%
Months Months
Time to Progression by PET and modified CT criteria
Non-responder
+ + + +++ + ++++++ +++ +
++++++ +++
++++ +++++++++++ +++
++++++ +
++ + +++ + + + + + ++ +++ ++++++++++ ++++ +++++++ + +++++++ ++
Months
Time to Progression by RECIST
302724211815129630
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.9
.8
.7
.6
.5
.4
.3
.2
.1
0 Nonresponders n=54 Responders n=44
P = 0.1
Response Rate 45%
Time to Progression: RECISTN=98
+ + ++++ +++++ ++ + ++++++++++++++ + +++++++++++++++++++++ ++
+++++++++++++++++++++++++ ++++
+
+
+++
+
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++
+ +
+ + +++ +
Months
Time to Progression by Our Criteria
302724211815129630
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.9
.8
.7
.6
.5
.4
.3
.2
.1
0
Nonresponders n=17Responders n=81
P = 0.0002
Response Rate 83%
Time to Progression: Modified CTN=98
Surveillance
Progression
• Increase in tumor size
• Appearance of a new lesion at the site of primary tumor
• Appearance metastatic lesions
Pre-Treatment2 Months Post
8 Months Post
11 Months Post
10 Months Post 17 Months Post 21 Months Post
27 Months Post
Progression in GIST
• “Increase in tumor size”
• Appearance of a new lesion at the site of primary tumor
• Appearance metastatic lesions
• ““Appearance of new intra-tumoral nodulesAppearance of new intra-tumoral nodules””
We do need FDG PET.
Pre-Treatment 2 Months Post
43 HU 30 HU
• RECIST underestimates the tumor response.
• Subjective evaluation using changes in tumor nodules, density, tumor vessels, in addition to change in size is the best criteria on CT and is reproducible.
• CT density alone can be a good indicator in early, quantitative tumor response evaluation.
Conclusions
Conclusions
• Objective evaluation using a combination of tumor density (15% change) and modified tumor size criteria (10% change) is promising in early tumor response evaluation and has a prognostic value.
• FDG PET should be performed whenever the CT findings are inconclusive or inconsistent with the clinical presentation.
It's Time To Re-visit Tumor Response Criteria !!
Acknowledgements
• Division of Diagnostic Imaging:
Chusilp Charnsangavej, M.D. Silvana C. Faria, M.D.Eric P. Tamm, M.D. Evelyn M. Loyer, M.D.Kazama Toshiki, M.D.
• Division of Nuclear Medicine:
Donald A. Podoloff, M.D.Homer A. Macapinlac, M.D.
• Department of Sarcoma Medical Oncology:
Robert S. Benjamin, M.D.
Sarcoma Center Team
• Department of Biostatistics:
Marcella M. Johnson, M.S.
Data Analysis: CT
Variables Response Analysis
Size (cm) RECIST* PD, SD, PR, CR
Density (HU) Grade 1-4
(median:13% )
G1 -12% (worse)
G2 -11% - 11%
G3 12- 31%
G4 32% (best)
OTR**
(size, density,
vessels, nodules)
Grade 1-4 G1 worse, G2 stable
G3 better, G4 best
**OTR – overall tumor response *JNCI 92(3); 205, 2000
OTS vs. SUV
No. Patients
by Change in SUVmax
No. Patients by Changes in OTS Total
No. of
PatientsGrade 1 Grade 2 Grade 3 Grade 4
Grade 1 0 2 0 0 2
Grade 2 6 0 0 0 6
Grade 3 0 0 1 0 1
Grade 4 0 1 4 15 20
Note. - The data were analyzed for the 29 patients who underwent both CT and FDG PET.
P = 0.0001*, Chi-Square Test
*Statistically significant.
HU vs. SUV
No. Patients
by Change in SUVmax
No. Patients by Changes in HU Total
No. of
PatientsGrade 1 Grade 2 Grade 3 Grade 4
Grade 1 0 1 1 0 2
Grade 2 1 4 1 0 6
Grade 3 0 1 0 0 1
Grade 4 2 4 4 10 20
Note. - The data were analyzed for the 29 patients who underwent both CT and FDG PET.
P = 0.3088, Chi-Square Test
ReproducibilityN = 35
Methods and Materials (II)
• Two radiologists who were not participated in initial analysis of CT images
• Overall Tumor Status (OTS)
• The results of two radiologists were compared with each other.
0
20
40
60
80
100Size
0
2
4
6
8
10
0
2
4
6
8
10
Pre-treatment
8 Wks Post-treatment
Mean SUVmax
Mean HUP < 0.0001, t-test P < 0.0001, t-test
P < 0.0001, t-test
Reader A vs. B
Reader A Reader B
Grade 1 Grade 2 Grade 3 Grade 4
Grade 1 0 0 0 0
Grade 2 1 2 2 0
Grade 3 0 0 11 0
Grade 4 0 0 12 7
P* = 0.0002, Chi-Square Test, rtau** = 0.5782
*Statistically significant. ** Kendall’s Tau correlation.
Note – Grades are based on OTR at 8 wks post-treatment.
OTS vs. SUV
No. Patients
by Change in SUVmax
No. Patients by Changes in OTS Total
No. of
PatientsGrade 1 Grade 2 Grade 3 Grade 4
Grade 1 0 2 0 0 2
Grade 2 0 0 1 0 1
Grade 3 0 1 0 0 1
Grade 4 0 1 10 20 31
Note. - The data were analyzed for the 35 patients who underwent both CT and FDG PET.
P = 0.0001*, Chi-Square Test
*Statistically significant.
EatoEaton 411286
Pre-Treatment
24 Months Post
2 Months Post
27 Months Post
Discrepancy(?): HU vs. SUVmax
• Development of intratumoral hemorrhage
• Definition of ROI
• EORTC guideline
528671
“KIT” Receptor
Tyrosine Kinase Receptor Blocker
+
• RECIST underestimates the tumor response in GIST.
• Subjective evaluation using changes in tumor nodules, density, tumor vessels, in addition to change in size is the best criteria on CT and is reproducible.
Conclusions
Conclusions
• Objective evaluation using a combination of tumor density (15% change) and modified tumor size criteria (10% change) is promising in early tumor response evaluation and has a prognostic value.
• FDG PET should be performed whenever the CT findings are inconclusive or inconsistent with the clinical presentation.