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

+++ ++ ++ ++ ++++++++++ +++++++++++++++

+

++

++

302724211815129630

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.9

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.5

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.2

.1

0

+++ ++ ++ ++ +++++++++++++++++++++++

+

++

++ +

302724211815129630

1

.9

.8

.7

.6

.5

.4

.3

.2

.1

0

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

1

.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

+ + ++++ +++++ ++ + ++++++++++++++ + +++++++++++++++++++++ ++

+++++++++++++++++++++++++ ++++

+

+

+++

+

+

++

+ +

+ + +++ +

Months

Time to Progression by Our Criteria

302724211815129630

1

.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.