Gastrointestinal Stromal

Tumor(GIST)

Dr. Amit Goswami

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?
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
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
Clinical Presentation
Non specific
Depends on site
GIST of GIT: GI bleeding MC
Others
-Abd. Mass
-Pain abdomen
-Abd.distension
-Intestinal obstruction
Asymptomatic:30%
 Pathology
Most commonly involves muscularis propria
Ulceration:50%
Well circumscribed
Cut surface: Tan/Grey, fibrous to fleshy
Spindle cell type: MC
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%)
 M. Miettinen, et al. Am J Surg Pathol. 2005
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
 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

MRI
Solid portion-low intensity on T1 weighted and high
intensity on T2 weighted images
Enhancement with gadolinium
Endoscopic Ultrasound
Smooth protrusion of bowel wall lined by normal
mucosa
Hypoechoic mass contiguous with fourth hypoechoic
layer(muscularis propria)
Benign Vs Malignant
Endoscopy
Gastric and colorectal GIST
Submucosal mass
Pre-op Biopsy
Usually not done
-Tumor seedling
-Bleeding
Endoscopic biopsy
-Less bleeding
-Confirm diagnosis
 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):S129
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
 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):
171723.
WinfieldRD,HochwaldSN,VogelSB,etal. Presentation and management of gastrointes-
tinal stromaltumors of the duodenum.AmSurg2006;72(8):71922[discussion:7223

WayneJD,BellRHJr.Limited gastric resection.SurgClinNorthAm2005;85(5):100920,

vii.
Small intestine
Duodenum: Partial duodenal resection/Whipples
Small Intestine: Segmental resection
Colorectum
Colon: Colectomy
Rectum: Anterior resection/Abdominoperineal
resection
Extra-intestinal: En block resection with adequate
margin
Berman J,OLeary 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
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
 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
 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):283341.
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
 Summary
Regular follow up
Imatinib mesylate ( both neoadjuvant and adjuvant)
Definite role Improved outcome
Problem - Resistance to imatinib
High recurrence
Currently Available Trials

Neoadjuvant study
RTOG S-0132/ACRIN 6665
Patients with recurrent or measurable peritoneal
disease
8 wks Imatinib followed by resection
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
Thank you