• GIST may occur anywhere along the GI tract or elsewhere in the abdomen or retroperitoneum

60%Stomach

25%Small

intestine

Colon/Rectum (5%)Other (mesentery, retroperitoneum)

8%

Esophagus (2%)

Adapted from: Corless et al. J Clin Oncol 2004;22:3813-25.

Major sites of GIST metastases:

liverperitoneumbone lung

GIST: Clinical Presentation

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.

GIST Evaluation Factors for Consideration

RTK Mutation Frequencies

Exon 9 (10%)

Exon 11 (67%)

Exon 13 (1%)

Exon 8 (<1%)

Exon 17 (1%)

Exon 12 (1%)

Exon 14 (<1%)

Exon 18 (5%)

KIT (80%) PDGFRA (5-8%)

Adapted from Hurlbut D. GIST Consensus Meeting 2007, Ottawa.

GIST Imaging

Image reprinted with permission from Lau et al. Clin Radiol 2004;59:487-98.

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.

Rates of RFS were predicted bymitotic index and tumour size

0

0.25

0.50

0.75

1.0

20 40 60 80Months

3 mitoses/30 HPF

>3 to 15 mitoses/30 HPF

>15 mitoses/30 HPFP=0.0001

0

Rec

urre

nce-

free

sur

viva

l

Mitotic index

Primary GIST: Risk Factors for Recurrence After Surgery

Singer et al. J Clin Oncol 2002;20:3898-905.

Adapted with permission from ASCO.

0

0.25

0.50

0.75

1.0

0 20 40 60 80

<5 cm

5-10 cm

>10 cm

P=0.03

Months

Rec

urre

nce-

free

sur

viva

l

Tumour size

The ACOSOG Z9001 Study, which randomized 644 patients to a TK inhibitor or placeboafter 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=0.0000014 for active treatment vs. placebo).

Adapted from: DeMatteo et al. ASCO 2007, Abs 10079.

P=0.0000014

ACOSOG Z9001 Study: Relapse Events at One Year

Adapted from van der Zwan SM, DeMatteo RP. Cancer 2005;104:1781-8.

Under clinical investigation:

- Nilotinib- RAD001- PKC412

No metastasis

Surgery

Post-operativeimatinib (adjuvant)

Recurrent disease

ProgressionResponse or stable disease

Surgery? Sunitinibor surgery?

Primary disease

Metastasisor unresectable

Imatinib

Treatment Algorithm for Patients with Primary Metastatic or Recurrent GIST