1. Major sites of GIST metastases:
GIST: Clinical Presentation
GIST may occur anywhere along the GI tract or elsewhere in the abdomen or retroperitoneum
Esophagus (2%)
Colon/Rectum (5%)
Other (mesentery, retroperitoneum) 8%
Major sites of GIST metastases:
liver
peritoneum
bone
lung
25%
Small
intestine
60%
Stomach
Adapted from: Corless et al. J Clin Oncol 2004;22:

2. GIST Evaluation Factors for Consideration
GIST histologic type (spindle/epithelioid/mixed)
KIT-positive/-negative
Biologic risk potential (low/intermediate/high)
Tumour size and location (1 section/1 cm tumour)
Cellularity (low/moderate/high), cellular atypia (mild/moderate/marked)
Mitotic count/50 HPF
Tumour necrosis
Mucosal ulceration
Lympho-vascular invasion
Margin status
Adapted from Marginean C. GIST Consensus Meeting 2007, Ottawa.

3. RTK Mutation Frequencies
KIT (80%)
PDGFRA (5-8%)
Exon 8 (<1%)
Exon 9 (10%)
Exon 11 (67%)
Exon 12 (1%)
Exon 13 (1%)
Exon 14 (<1%)
Exon 17 (1%)
Exon 18 (5%)
Adapted from Hurlbut D. GIST Consensus Meeting 2007, Ottawa.

4. GIST Imaging CT
Delineates the large exophytic masses and local and distant metastases
Guides tissue biopsy
PET
Differentiates tissues and assesses tumor metabolic activity
For early treatment-response evaluation
Large heterogeneous duodenal GIST (D)
with multifocal hepatic metastases (M).
The biliary tree and pancreatic duct are not dilated.
Image reprinted with permission from Lau et al. Clin Radiol 2004;59:

5. Primary GIST: Risk Factors for Recurrence After Surgery
Rates of RFS were predicted by
mitotic index and tumour size
0.25
0.50
0.75
1.0 20 40 60 80
Months
3 mitoses/30 HPF
>3 to 15 mitoses/30 HPF
>15 mitoses/30 HPF
P=0.0001
Recurrence-free survival
Mitotic index
0.25
0.50
0.75
1.0 20 40 60 80
<5 cm
5-10 cm
>10 cm
P=0.03
Months
Recurrence-free survival
Tumour size
Singer et al. J Clin Oncol 2002;20:
Adapted with permission from ASCO.

6. ACOSOG Z9001 Study: Relapse Events at One Year
The ACOSOG Z9001 Study, which randomized 644 patients to a TK inhibitor or placebo
after GIST surgical resection, was halted early when the relapse rate was 67.5% lower
at one year in the arm receiving the TK inhibitor (hazard ratio=0.325;P= for
active treatment vs. placebo).
Adapted from: DeMatteo et al. ASCO 2007, Abs

7. Treatment Algorithm for Patients with Primary Metastatic or Recurrent GIST
Primary disease
Recurrent disease
No metastasis
Metastasis or unresectable
Imatinib
Surgery
Response or stable disease
Progression
Post-operative imatinib (adjuvant)
Under clinical investigation:
- Nilotinib - RAD001 - PKC412
Sunitinib or surgery?
Surgery?
Adapted from van der Zwan SM, DeMatteo RP. Cancer 2005;104: