1. Response Evaluation of Gastrointestinal Stromal Tumors (GIST)
Haesun Choi, M.D.
Diagnostic Imaging
The University of Texas MD Anderson
Cancer Center, Houston, TX

2. Gastrointestinal Stromal Tumor (GIST)
deadly disease
therapeutic options

3. + “KIT” receptor Tyrosine kinase receptor blocker Kinase domains
Chris Corless, M.D. +
Imatinib mesylate
Tyrosine kinase
receptor blocker

4. Thessasse et al. JNCI 92(3); 205, 2000
“Computed Tomography (CT) and Magnetic
Resonance Imaging (MRI) are the best currently
available and most reproducible methods for
measuring the target lesions …”
the recent guidelines for response evaluation in solid tumors, published in 2000
Thessasse et al. JNCI 92(3); 205, 2000

5. Fluorine-18-fluorodeoxyglucose Positron Emission Tomography (FDG PET)

6. 8/9/02
10/28/02

7. Pre-Treatment
Pre-Treatment

8. Computed Tomography (CT)
In general practice, CT remanins the modality of choice to monotor the disease.

9. Gastric GIST
Metastatic GIST

10. Small bowel GIST
Metastatic GIST

11. 6/01
HU 63
3.3 cm
8/01
HU 38
2.3 cm
10/01
HU 32
1.9 cm

12. Pre-Treatment
2 Months Post

13. Pre-Treatment
5 Days Post

14. 30 HU
43 HU
Pre-Treatment
2 Months Post

15. Methods and Materials (I)
CT vs. PET
PET: EORTC1999
Tumor size (cm)
Tumor density (HU)
“Overall tumor status (OTS)”
Total patients = 36
CT* and PET* = 29
*within a week of each other
Total lesions = 173
Liver: 116
Peritoneum: 52
Pleura: 5

16. Subjective Tumor Response Evaluation: OTS
Pre-Treatment
Size +
tumor vessels
solid tumor
nodules
tumor density

17. Pre-Treatment
2 Months Post

18. Objective Tumor Response Evaluation
Size
Mean HU
Mean SUVmax
P = , t-test
P<0.0025, t-test
Pre-treatment
8 Wks Post-treatment

19. No. of Patients by Changes in Size*
Size vs. SUV
No. Patients
by Changes in SUVmax**
No. of Patients by Changes in Size*
Total
No. of
Patients PD SD PR CR
Grade 1 2
Grade 2 1 5 6
Grade 3
Grade 4 15 4 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

20. 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%): % 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)

21. Changes in Size and HU on CT vs. Tumor Response on FDG PET
Total number of patients = 40
Tumor response by PET
Patients with
 10% decrease in size (%)
 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)
n – number of patients

22. Modified CT Criteria PET response: CT response: SUV < 2.5, 70%
HU  -15%, Size  -10% 1 .9 .8 .7 .6 .5 .4 .3 .2 .1 1 .9 .8 .7 .6 .5 .4 .3 .2 .1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
P = 0.03 + + + + + + + + + + + + + + + + + + + +
P = 0.03 + + + + +
Responder
Responder
Non-responder
Non-responder 30 27 24 21 18 15 12 9 6 3 30 27 24 21 18 15 12 9 6 3
Months
Months
Time to Progression by PET and modified CT criteria

23. Time to Progression: RECIST
Response Rate 45%

24. Time to Progression: Modified CT
Response Rate 83%

25. Surveillance

26. Progression Increase in tumor size
Appearance of a new lesion at the site of primary tumor
Appearance metastatic lesions

27. Pre-Treatment
2 Months Post
8 Months Post
11 Months Post

28. 10 Months Post
17 Months Post
21 Months Post
27 Months Post

29. “Appearance of new intra-tumoral nodules”
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 nodules”

30. We do need FDG PET.

31. 30 HU
43 HU
Pre-Treatment
2 Months Post

32. Conclusions 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.

33. 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.

34. It's Time To Re-visit Tumor Response Criteria !!

35. Acknowledgements Chusilp Charnsangavej, M.D. Donald A. Podoloff, M.D.
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.

38. 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%
G %
G4  32% (best)
OTR**
(size, density,
vessels, nodules)
G1 worse, G2 stable
G3 better, G4 best
**OTR – overall tumor response *JNCI 92(3); 205, 2000

39. No. Patients by Changes in OTS
OTS vs. SUV
P = *, Chi-Square Test
No. Patients
by Change in SUVmax
No. Patients by Changes in OTS
Total
No. of
Patients
Grade 1
Grade 2
Grade 3
Grade 4 2 6 1 4 15 20
horozontal
vertical
*Statistically significant.
Note. - The data were analyzed for the 29 patients who underwent both CT and FDG PET.

40. No. Patients by Changes in HU
HU vs. SUV
P = , Chi-Square Test
No. Patients
by Change in SUVmax
No. Patients by Changes in HU
Total
No. of
Patients
Grade 1
Grade 2
Grade 3
Grade 4 1 2 4 6 10 20
Note. - The data were analyzed for the 29 patients who underwent both CT and FDG PET.

41. Reproducibility N = 35

42. 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.

43. Mean HU Size Mean SUVmax Pre-treatment 8 Wks Post-treatment
P < , t-test
P < , t-test
Mean SUVmax
P < , t-test
Pre-treatment
8 Wks Post-treatment

44. P* = 0.0002, Chi-Square Test, rtau** = 0.5782
Reader A vs. B
P* = , Chi-Square Test, rtau** =
Reader A
Reader B
Grade 1
Grade 2
Grade 3
Grade 4 1 2 11 12 7
There was a good agreement between the two readers through the grades.
*Statistically significant. ** Kendall’s Tau correlation.
Note – Grades are based on OTR at 8 wks post-treatment.

45. No. Patients by Changes in OTS
OTS vs. SUV
P = *, Chi-Square Test
No. Patients
by Change in SUVmax
No. Patients by Changes in OTS
Total
No. of
Patients
Grade 1
Grade 2
Grade 3
Grade 4 2 1 10 20 31
And also again the changes in ODS correlated well with the changes in SUVmax based on consensus.
*Statistically significant.
Note. - The data were analyzed for the 35 patients who underwent both CT and FDG PET.

46. Pre-Treatment
2 Months Post
EatoEaton
24 Months Post
27 Months Post

47. Discrepancy(?): HU vs. SUVmax
Development of intratumoral hemorrhage
Definition of ROI
EORTC guideline

48. 528671

49. Tyrosine Kinase Receptor Blocker
“KIT” Receptor +
Tyrosine Kinase Receptor Blocker

50. Conclusions 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.

51. 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.