Management of GIST

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Management of GIST Powered By Docstoc
					Management of GIST

    Dr Kwan Ming Wa
    Tuen Mun Hospital
                 Contents
Mainly concern about
   Oncogensis
   Surgical treatment
   Targeted therapy
                Introduction
GIST
   the most common Sarcoma of the GI tract
   derived from the Interstitial cells of Cajal
                     Oncogenesis of GIST
  Mutated KIT receptor become autonomous
  and cell proliferation become uncontrolled




    KIT
  Receptor
                                                                  Gene
                                                                expression

                                          Signal-Transduction
                                              ATP ADP



  Signal
 Molecule                                   Plasma Membrane

Earl W. Sutherland (Nobel Prize – 1971)
Understanding of the oncogenesis
          is the key to
 the advances of diagnosis and
        targeted therapy
  Differentiation of GIST from
    smooth muscle tumour


                KIT   CD34   Desmin


GIST            +     60-70% rare


Smooth muscle   _     10-15% +
tumour
        Targeted therapy (Glivec)
               Competitive inhibition of Tyrosine Kinase


Autonomous
KIT Receptor
                           ATP ADP
                                                             Gene
                                                           expression




                              Plasma Membrane
     Clinical features of GIST
Incidence
   Worldwide 10-20/ million
   Tuen Mun ~13 cases/ year
Median age at 60
Sex ratio 1:1
            Location of GIST
Site              worldwide   Tuen Mun

stomach           40-60 %     55%

Small intestine   20-40%      29%
Colon and
                  5-15%       8%
rectum
esophagus         <5%         2%

others            5-7%        7%
               Presentation
GI Bleeding
   the most common presenting symptom
Mass effect
   when tumour is large enough
Small GIST
   Usually found incidentally
Symptoms related to gastric GIST
         in TuenMun

     Asymptomatic
        3.7%          Others
                      11.1%
     Abdominal
       Mass                                   Malaena
       3.7%                                    44.4%

     Abdominal
        Pain
       18.5%
                 Anaemia       Haematemesis
                  7.4%            11.1%
           Preoperative biopsy
             Not advocated

GIST is highly vascular and friable
   Risk of bleeding
   Risk tumour rupture
   Risk tumour dissemination and early recurrence
Imaging for diagnosis and staging
CT scan, endoscopy and EUS are commonly
used to diagnose GIST
    A well circumscribed, vascular mass associated with
     stomach/ intestine

Staging primary GIST
     CT scan and CXR is sufficient
    metastasis is usually confined to peritoneum and the
     liver
For complicated disease, PET-CT
    Recurrent disease/ extraperitoneal metastasis
              Surgery
The primary treatment for resectable GIST
The goal is complete resection of the
mass without disruption of the
pseudocapsule
GIST generally displace rather than
infiltrating the surrounding structure
Achieving negative margin is usually
possible
     Dissection of lymph node
             does not
prolong survival or delay recurrence



 Connolly EM, Br J Surg 2003
 Sammiian L, Am Surg 2004
Type of operation for gastric GIST
          in Tuen Mun
                  20            19
                  18

                  16

                  14

                  12

   No. of Patients 10

                   8

                   6
                   4
                                                   3                  3
                                                                                           2
                   2
                   0
                        Laparotomy+wedge    Laparoscopic    Partial gastrectomy   Total gastrectomy
                             excision      wedge excision
                                               Types of Operation
Outcome of gastric GIST resection
            in TMH
Outcome after complete resection
5yr survival (overall) : 48-65%
Poor outcome is associated with
    Big tumour size (>5cm)
    High mitotic figure (>5/50HPF)
Example of excising a big GIST
1 year later..
Conventional adjuvant therapy
Chemotherapy: refractory
Radiotherapy: limited use
           Targeted therapy
Evidence of benefit in
   Treatment of advanced GIST
   As adjuvant to primary tumour resection
Advanced GIST treated with Glivec
                U.S./     EORTC
                Finland   study (n=36)
                study
                (n=147)
  Partial       54%       69%
  response
  Stable        28%       19%
  disease
  progression   14%       11%
 ACOSOG Z9001: A randomized, double blind
 study of adjuvant Glivec versus placebo following
 resection of primary GIST

                                         10 years or until death
 Design:


                            Placebo x 1 year
                                                                       F
Primary                                                                O
           Complete Gross                          Glivec 400mg        L
  GIST                      Recurrence
             Resection                          (or 800mg) x 2 years   L
(≥ 3 cm)                                                               O
                                                                       W
                            Glivec 400mg
                               x 1 year
             ACOSOG Trial Prematurely Stopped
    Due to Superior Rates of Recurrence Free Survival (RFS)

                                                  with Glivec


       Data monitoring committee evaluated data on >600 pts with
       complete resection of primary GIST

       At 1 year follow-up, 97% of patients on Glivec arm were free of
       recurrence compared with 83% of patients on placebo arm

       Approximately 65% less likely to experience recurrence within two
       years

       All patients will be unblinded, and patients in the placebo arm will be
       offered 1 year of Glivec



Available at: http://www.cancer.gov/newscenter/pressreleases/GISTtrial
               Treatment model
 Normal      Pre-Cancer      Cancer           Metastatic Cancer




Treatment
Stage       prevention
                          Primary +/-
                           Adjuvant     systemic
                                         therapy   1st Line   2rd Line
Thankyou

				
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posted:7/30/2012
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