Gastrointestinal stromal tumors (GISTs) are rare tumors that originate from the gastrointestinal tract. They most commonly occur in the stomach. Surgical resection is the primary treatment, but molecular targeted therapy with imatinib is also used in advanced or unresectable cases. Imatinib has improved outcomes by reducing recurrence rates after surgery or controlling tumor growth. Ongoing clinical trials are further evaluating the neoadjuvant and adjuvant uses of imatinib to improve prognosis.

1. Dr. Amit Goswami

2. Introduction
 Mazur and Clark(1983)
 Mesenchymal tumor
 From embryological mesoderm of gastrointestinal
tract
 <1% of all GIT tumors
 Hirota et.al(1998):Mutation in KIT
 Interstitial cell of Cajal: Common precursor?

3. Demography
 Incidence:15-20 per million
 M>F
 Age:40-80yrs(median age 60yrs)
 Mostly sporadic
 Familial( Neurofibromatosis, Carney triad)
Eisenberg BL,Judson I.Surgery and imitanib in the management of GIST:emerging approaches to adjuvant and
neoadjuvant therapy.Ann Surg Oncol 2004;11:465-475
Gold JS,Matteo RP.Combined surgical and molecular therapy: The gastrointestinal stromal tumor model.Ann surg
2006;244:176
DeMatteo RP,Lewis JJ,Leung D et al.Two hundred Gastrointestinal stromal tumors: recurrence patterns and prognostic
factors for survival.Ann surg 2000;231(1):51-8
Takazawa Y,sakurai S,Sakuma Y et al.Gastrointstinal stromal tumors of neurofibromatosis type I.Am J surg Pathol
2005;29(6):755-63

4. Location
 Stomach :50% MC
 Esophagus:5%
 Small Intestine:25%
 Colon and rectum:10%
 Extra-intestinal:10%
Rubin BP.Gastrointestinal stromal tumors: an update.Histopathology 2006;48:83-96
Clin Cancer Res 9(9):2003

5. Clinical Presentation
 Non specific
 Depends on site
 GIST of GIT: GI bleeding MC
 Others
-Abd. Mass
-Pain abdomen
-Abd.distension
-Intestinal obstruction
 Asymptomatic:30%

6. Pathology
 Most commonly involves muscularis propria
 Ulceration:50%
 Well circumscribed
 Cut surface: Tan/Grey, fibrous to fleshy
 Spindle cell type: MC

7. Malignant Potential
• Features favoring benign lesions :
– Size less than 5 cm
– Low number of mitosis per HPF
– No mucosal invasion
– Low cellularity
– Low markers of cell proliferation
 Tumor site: Stomach vs bowel
 Site of metastasis: Liver(50%),peritoneum(20-40%)

8.  M. Miettinen, et al. Am J Surg Pathol. 2005

9. Diagnosis
 Clinical, radiological and pathological characteristics
 CECT- Imaging modality of choice
 Endoscopic ultrasound: Small tumor
 MRI: Rectal GISTs
 PET scan: Assessment of therapy
Blay JY,Bonvalot S,Casali P et al.Consensus meeting for the management of gastrointestinal stromal tumors.Ann
Oncology 2005;16:566-578

10. CECT
 Heterogenous appearance with central necrosis and
areas of cystic degeneration
 Extension to other structures
 Distant spread
 Low attenuating liver metastasis
King DM.The radiology of gastrointestinal stromal tumors(GIST).Cancer Imaging 2005;5:150-156

11. MRI
 Solid portion-low intensity on T1 weighted and high
intensity on T2 weighted images
 Enhancement with gadolinium

12. Endoscopic Ultrasound
 Smooth protrusion of bowel wall lined by normal
mucosa
 Hypoechoic mass contiguous with fourth hypoechoic
layer(muscularis propria)
 Benign Vs Malignant

13. Endoscopy
 Gastric and colorectal GIST
 Submucosal mass

14. Pre-op Biopsy
 Usually not done
-Tumor seedling
-Bleeding
 Endoscopic biopsy
-Less bleeding
-Confirm diagnosis

15. Treatment
 Surgical resection is preferred
 Locally advanced: Targeted therapy
 Radiation/Chemotherapy: Ineffective
DemetriGD,BenjaminRS,BlankeCD,etal.NCCNTaskForcereport:managementof
patientswithgastrointestinalstromaltumor(GIST)dupdateoftheNCCNclinicalpractice
guidelines.JNatlComprCancNetw2007;5(Suppl2):S1–29

17. Surgical therapy
 Complete en-block removal
 Site specific
 Avoidance of tumor rupture
 Lymphadenectomy not advocated
 Final goal: complete tumor resection with a negative
margin, intact pseudocasule
 Positive resection margin: Re-excision
DeMatteo RP,Lewis JJ,Leung D et al.Two hundred Gastrointestinal stromal tumors: recurrence patterns and prognostic
factors for survival.Ann surg 2000;231(1):51-8
Blay JY,Bonvalot S,Casali P et al.Consensus meeting for the management of gastrointestinal stromal tumors.Ann
Oncology 2005;16:566-57

18. Site specific surgery
 Esophagus: esophagestectomy/esophageal sparing
wide local excision
 Stomach
Small-wedge resection
Large-subtotal/total gastrectomy
BlumMG,BilimoriaKY,WayneJD,etal.S urgical considerations for the management and
Resection of esophageal gastrointestinal stromal tumors.AnnThoracSurg2007;84(5):
1717–23.
WinfieldRD,HochwaldSN,VogelSB,etal. Presentation and management of gastrointes-
tinal stromaltumors of the duodenum.AmSurg2006;72(8):719–22[discussion:722–3
WayneJD,BellRHJr.Limited gastric resection.SurgClinNorthAm2005;85(5):1009–20,
vii.

19.  Small intestine
Duodenum: Partial duodenal resection/Whipple’s
Small Intestine: Segmental resection
 Colorectum
Colon: Colectomy
Rectum: Anterior resection/Abdominoperineal
resection
 Extra-intestinal: En block resection with adequate
margin
Berman J,O’Leary TJ.Gastrointestinal stromal tumor workshop.Hum Pathol 2001;32:578-582
Blay JY,Bonvalot S,Casali P et al.Consensus meeting for the management of gastrointestinal stromal tumors.Ann Oncology
2005;16:566-57

24. Molecular targeted therapy(TKI)
 Joensuu and colleague(2001)
 Success: Lack of progression
 Standard starting dose :400 mg/day
 Ideal dose: not determined
 Neoadjuvant role:
-Severe organ dysfunction (eg: for rectal or
esophageal tumors)
-Negative margin difficult
 Resistance: Primary/Secondary

25. Imitanib trials
TRIALS DOSE PARTIAL STABLE PROGRES COMMENTS
RESPONSE DIS S
EORTC 400,600,800 51% 31% 8% TTR 1WK
2001,2002 or 1000mg/d MTD 800mg/d
US 400mg/d 67% 16% 17% No difference
MULTICENTER 600mg/d 66% 18% 8%
2002,2004
EORTC 400mg/d 50% 32% 13% 32% severe tox
2003 800mg/d 54% 32% 8% 50%severe tox
Improved PFS
for 800mg/d
INTERGROUP 400mg/d 49% 22% 36%severe tox
2003 800mg/d 48% 22% 52%severe tox
No difference in
PFS
TTR=Time to recurrence, MTD=Maximal tolerated dose, PFS=Progression free survival
GoldJS,DeMatteoRP.Combined surgical and moleculartherapy:the gastrointestinal stromal tumor
model. AnnSurg2006;244:176

26. Newer Approaches
 SUNITINIB: multitargated tyrosine kinase inhibitor
 HACE/RFA: liver metastasis
 Other TKI:
-Nilotinib
-Mastitinib
-BMS-354,825
KobayashiK,GuptaS,TrentJC,etal.Hepatic artery chemoembolization for 110
Gastrointestinal stromal tumors.Cancer2006;107(12):2833–41.

27. Summary
 Rare
 Mostly sporadic and single
 Anywhere in GI Tract- Stomach MC
 Evaluation – EUS, CT, PET CT
 Varied clinical presentation- GI bleed MC
 Treatment of choice – Surgery, potentially
curative

28. Summary
 Regular follow up
 Imatinib mesylate ( both neoadjuvant and adjuvant)
Definite role Improved outcome
 Problem - Resistance to imatinib
High recurrence

29. Currently Available Trials
Neoadjuvant study
 RTOG S-0132/ACRIN 6665
 Patients with recurrent or measurable peritoneal
disease
 8 wks Imatinib followed by resection

30. Currently Available Trials
Adjuvant study EORTC 64024
 Patients with R0 resections eligible
 Patients stratified according to risk factors
 Patients randomized to either
 Imatinib 400 mg/day X 2 years
 Observation