GIST Clinical Presentation GIST may occur anywhere along

GIST Evaluation Factors for Consideration § GIST histologic type (spindle/epithelioid/mixed) § KIT-positive/-negative § Biologic

RTK Mutation Frequencies KIT (80%) PDGFRA (5 -8%) Exon 8 (<1%) Exon 9 (10%)

GIST Imaging CT • Delineates the large exophytic masses and local and distant metastases

Primary GIST: Risk Factors for Recurrence After Surgery Rates of RFS were predicted by

ACOSOG Z 9001 Study: Relapse Events at One Year P=0. 0000014 The ACOSOG Z

Treatment Algorithm for Patients with Primary Metastatic or Recurrent GIST Primary disease No metastasis

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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% 60% Stomach 25% Small intestine Adapted from: Corless et al. J Clin Oncol 2004; 22: 3813 -25. Major sites of GIST metastases: liver peritoneum bone lung

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.

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.

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: 487 -98.

Primary GIST: Risk Factors for Recurrence After Surgery Rates of RFS were predicted by mitotic index and tumour size Tumour size 3 mitoses/30 HPF 1. 0 0. 75 >3 to 15 mitoses/30 HPF 0. 50 0. 25 P=0. 0001 0 0 20 >15 mitoses/30 HPF 40 Months 60 Singer et al. J Clin Oncol 2002; 20: 3898 -905. Adapted with permission from ASCO. 80 Recurrence-free survival Mitotic index 1. 0 <5 cm 0. 75 5 -10 cm 0. 50 >10 cm 0. 25 P=0. 03 0 0 20 40 Months 60 80

ACOSOG Z 9001 Study: Relapse Events at One Year P=0. 0000014 The ACOSOG Z 9001 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=0. 0000014 for active treatment vs. placebo). Adapted from: De. Matteo et al. ASCO 2007, Abs 10079.

Treatment Algorithm for Patients with Primary Metastatic or Recurrent GIST Primary disease No metastasis Recurrent disease Metastasis or unresectable Imatinib Surgery Post-operative imatinib (adjuvant) Response or stable disease Progression Surgery? Adapted from van der Zwan SM, De. Matteo RP. Cancer 2005; 104: 1781 -8. Under clinical investigation: Sunitinib or surgery? - Nilotinib - RAD 001 - PKC 412