Gastrointestinal stromal tumor(gist)
-
Upload
dradg -
Category
Health & Medicine
-
view
4.822 -
download
1
description
Transcript of Gastrointestinal stromal tumor(gist)
![Page 1: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/1.jpg)
Gastrointestinal Stromal Tumor(GIST)
Dr. Amit Goswami
![Page 2: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/2.jpg)
IntroductionMazur and Clark(1983)Mesenchymal tumorFrom embryological mesoderm of
gastrointestinal tract<1% of all GIT tumorsHirota et.al(1998):Mutation in KITInterstitial cell of Cajal: Common precursor?
![Page 3: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/3.jpg)
DemographyIncidence:15-20 per millionM>FAge:40-80yrs(median age 60yrs)Mostly sporadicFamilial( 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
![Page 4: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/4.jpg)
Location
Stomach :50% MCEsophagus:5%Small Intestine:25%Colon and rectum:10%Extra-intestinal:10%
Rubin BP.Gastrointestinal stromal tumors: an update.Histopathology 2006;48:83-96Clin Cancer Res 9(9):2003
![Page 5: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/5.jpg)
Clinical PresentationNon specificDepends on siteGIST of GIT: GI bleeding MCOthers -Abd. Mass -Pain abdomen -Abd.distension -Intestinal obstruction Asymptomatic:30%
![Page 6: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/6.jpg)
PathologyMost commonly involves muscularis propriaUlceration:50%Well circumscribedCut surface: Tan/Grey, fibrous to fleshySpindle cell type: MC
![Page 7: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/7.jpg)
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 proliferationTumor site: Stomach vs bowelSite of metastasis:
Liver(50%),peritoneum(20-40%)
![Page 8: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/8.jpg)
M. Miettinen, et al. Am J Surg Pathol. 2005
![Page 9: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/9.jpg)
DiagnosisClinical, 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
![Page 10: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/10.jpg)
CECTHeterogenous appearance with central
necrosis and areas of cystic degenerationExtension to other structuresDistant spreadLow attenuating liver metastasis
King DM.The radiology of gastrointestinal stromal tumors(GIST).Cancer Imaging 2005;5:150-156
![Page 11: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/11.jpg)
MRI
Solid portion-low intensity on T1 weighted and high intensity on T2 weighted images
Enhancement with gadolinium
![Page 12: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/12.jpg)
Endoscopic UltrasoundSmooth protrusion of bowel wall lined by
normal mucosaHypoechoic mass contiguous with fourth
hypoechoic layer(muscularis propria)Benign Vs Malignant
![Page 13: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/13.jpg)
EndoscopyGastric and colorectal GISTSubmucosal mass
![Page 14: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/14.jpg)
Pre-op BiopsyUsually not done -Tumor seedling -BleedingEndoscopic biopsy -Less bleeding -Confirm diagnosis
![Page 15: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/15.jpg)
TreatmentSurgical resection is preferred
Locally advanced: Targeted therapy
Radiation/Chemotherapy: Ineffective
DemetriGD,BenjaminRS,BlankeCD,etal.NCCNTaskForcereport:managementofpatientswithgastrointestinalstromaltumor(GIST)dupdateoftheNCCNclinicalpractice
guidelines.JNatlComprCancNetw2007;5(Suppl2):S1–29
![Page 16: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/16.jpg)
![Page 17: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/17.jpg)
Surgical therapyComplete en-block removalSite specificAvoidance of tumor ruptureLymphadenectomy not advocatedFinal goal: complete tumor resection with a
negative margin, intact pseudocasulePositive 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
![Page 18: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/18.jpg)
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 andResection 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.
![Page 19: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/19.jpg)
Small intestine
Duodenum: Partial duodenal resection/Whipple’s
Small Intestine: Segmental resectionColorectum
Colon: Colectomy
Rectum: Anterior resection/Abdominoperineal
resectionExtra-intestinal: En block resection with
adequate marginBerman 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
![Page 20: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/20.jpg)
![Page 21: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/21.jpg)
![Page 22: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/22.jpg)
![Page 23: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/23.jpg)
![Page 24: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/24.jpg)
Molecular targeted therapy(TKI)Joensuu and colleague(2001)Success: Lack of progressionStandard starting dose :400 mg/dayIdeal dose: not determinedNeoadjuvant role: -Severe organ dysfunction (eg: for rectal
or esophageal tumors) -Negative margin difficultResistance: Primary/Secondary
![Page 25: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/25.jpg)
Imitanib trialsTRIALS DOSE PARTIAL
RESPONSESTABLE DIS
PROGRESS
COMMENTS
EORTC2001,2002
400,600,800 or 1000mg/d
51% 31% 8% TTR 1WKMTD 800mg/d
US MULTICENTER2002,2004
400mg/d600mg/d
67%66%
16%18%
17%8%
No difference
EORTC2003
400mg/d800mg/d
50%54%
32%32%
13%8%
32% severe tox50%severe toxImproved PFS for 800mg/d
INTERGROUP2003
400mg/d800mg/d
49%48%
22%22%
36%severe tox52%severe toxNo difference in PFS
TTR=Time to recurrence, MTD=Maximal tolerated dose, PFS=Progression free survivalGoldJS,DeMatteoRP.Combined surgical and moleculartherapy:the gastrointestinal
stromal tumor model. AnnSurg2006;244:176
![Page 26: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/26.jpg)
Newer ApproachesSUNITINIB: multitargated tyrosine kinase
inhibitorHACE/RFA: liver metastasisOther TKI: -Nilotinib -Mastitinib -BMS-354,825
KobayashiK,GuptaS,TrentJC,etal.Hepatic artery chemoembolization for 110Gastrointestinal stromal tumors.Cancer2006;107(12):2833–41.
![Page 27: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/27.jpg)
SummaryRareMostly sporadic and singleAnywhere in GI Tract- Stomach MCEvaluation – EUS, CT, PET CTVaried clinical presentation- GI bleed MCTreatment of choice – Surgery, potentially
curative
![Page 28: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/28.jpg)
Summary Regular follow up Imatinib mesylate ( both neoadjuvant and
adjuvant) Definite role Improved outcome Problem - Resistance to imatinib
High recurrence
![Page 29: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/29.jpg)
Currently Available Trials
Neoadjuvant study RTOG S-0132/ACRIN 6665 Patients with recurrent or measurable
peritoneal disease 8 wks Imatinib followed by resection
![Page 30: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/30.jpg)
Currently Available TrialsAdjuvant 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
![Page 31: Gastrointestinal stromal tumor(gist)](https://reader033.fdocuments.in/reader033/viewer/2022061203/547d09c6b4af9fcd5b8b45a8/html5/thumbnails/31.jpg)
Thank you