WORKSHOP GIST

SEMARANG 14 SEPTEMBER 2013

INTESTINAL GIST
ANAMNESIS
Laki-laki 44 tahun,
12 bulan perut merasa tidak enak,kadang-kadang
mules, pernah berak kehitaman. Hanya diobatkan
ke dokter puskesmas
3 bulan teraba benjolan yang makin lama makin
membesar, perut terasa sebah dan mules sekali
dan berak hitam makin jelas
Nafsu makan kurang dan berat badan menurun
Riwayat family dengan tumor abdomen disangkal
PEMERIKSAAN FISIK
Laki-laki berat badan: 42 Kg, TB 165 cm, BMI :
15,44
Kurus, nampak pucat
Abdomen kembung ringan, terlihat bulging perut
dibagian tengah, gambaran dan gerakan usus
tidak terlihat.
Palpasi teraba tumor diameter sekitar 12 cm,
bulat dengan permukaan tidak rata, konsistensi
keras, nyeri tekan (-), relatif mobile
Auscultasi: Peristaltik normal, tidak terdengar
bising diatas tumor
LABORATORIUM
Hb 7,8 Mg%, Ht 24, Lekosit 6500
Alb 2,8 mg%, Glob 2,3 mg%
Na 134, K 3,2, Cl 98, Ca 2,10
Lain-lain baik.

DIAGNOSA BANDING
LYMPHOMA MALIGNA
HODGKIN DISEASE
SCWANOMA MALIGNA
LEIOMYOSARCOMA
INSTESTINAL GIST
PERLU KEPASTIAN DIAGNOSIS SEBELUM OPERASI?
PERSIAPAN PRA-BEDAH
ANEMIA:
BLOOD TRANFUSION

SEVERE MALNUTRITION
PRE-OPERATIVE NUTRITIONAL SUPPORT
LAPARATOMI
TUMOR USUS HALUS PERTENGAHAN
(PERBATASAN ILEUM-JEJENUM) SEKITAR 14
CM, KERAS, LN MESENTERIKA (-), PERITONEAL
SEEDING (-), METASTASE HEPAR (-)
TANDA PARTIAL OBSTRUKSI USUS (+)
DILAKUKAN RESEKSI USUS HALUS ISTAL DAN
PROKSIMAL TUMOR, ANASTOMOSIS END TO
END
PASCA BEDAH
PASIEN BAIK PULANG TANPA KOMPLIKASI

PA SPINDEL CELL TUMOR CURIGA GIST, BATAS
RESEKSI BEBAS TUMOR, MITOSIS(?)
IHC CD 117 (+)


PEMBAHASAN
Diagnostic procedure?
Grade?
Surgery?
Chemotherapy (preoperative? post-
operative?)
Prognosis?
DIAGNOSTIC PROCEDURE?
PREOPERATIVE DIAGNOSIS
ENDOSCOPY:
DOUBLE BALLON ENTEROSCOPY?
CAPSULE ENDOSCOPY?

LAPARATOMY/ LAPAROSCOPY BIOPSY?

NO NEED DIRECT LAPARATOMY &
RESECTION OR BIOPSY.
GRADING
POLSKIE ARCHIWUM MEDYCYNY WEWNTRZNEJ 2008; 118 (4)
HUMAN PATHOLOGY Volume33, No. 5 (May 2002)
NIH Classification for Risk of
Recurrence
Very Low Risk Low Risk Intermediate Risk High Risk
NIH consensus
criteria
1

Tumor size < 2 cm
Mitotic index < 5

Tumor size 2-5 cm
Mitotic index < 5

Tumor size 5-10 cm
Mitotic index < 5
OR
Tumor size < 5 cm
Mitotic index 6-10
Tumor size > 5 cm
Mitotic index > 5
OR
Tumor size > 10 cm
Mitotic index, any
OR
Tumor size, any
Mitotic index > 10
Modified NIH
consensus
classification
2

Any location:
Tumor size < 2 cm
Mitotic index 5

Any location:
Tumor size 2.1-5 cm
Mitotic index 5

Any location:
Tumor size < 5 cm
Mitotic index 6-10

Gastric:
Tumor size 2.1-5 cm
Mitotic index > 5
OR
Tumor size 5.1-10 cm
Mitotic index 5
Any location:
Tumor rupture
OR
Tumor size > 10 cm
OR
Mitotic index > 10
OR
Tumor size > 5 cm
Mitotic index > 5

Nongastric:
Tumor size 2.1-5 cm
Mitotic index > 5
OR
Tumor size 5.1-10 cm
Mitotic index 5
Abbreviations: Mitotic index, number of mitoses per 50 high-power fields; NIH, National Institutes of health.
1. Fletcher CD, et al. Hum Pathol. 2002;33(5):459-465; 2. Joensuu H. Hum Pathol. 2008;39(10):1411-1419.
24
GRADE
TUMOR > 10 CM
MITOTIC INDEX: NOT REPORTED
NEGATIVE MARGIN
LOCATION: NON GASTRIC

HIGH RISK GROUP FOR RECCURRENCE

SURGERY
Surgical treatment of gist
The radical surgical treatment is the most effective
treatment
The 5-year survival rate after surgery amounts to 2865%
It is not necessary to resect the regional lymph nodes
because GIST do not metastasize to the regional
lymphatic system
2040% of the surgery patients have intra-abdominal
dissemination or liver metastasis paliatif surgery
(sympotomatic treatment)
endoscopic dissection (submucosal-mucosal resection)
allows a radical therapy of small tumors without
malignancy features and limited to the submucosal layer.

POLSKIE ARCHIWUM MEDYCYNY WEWNTRZNEJ 2008; 118 (4)

CHEMOTHERAPY
Preoperative : need histological
diagnosis
PROGNOSIS
The 5-year survival rate after surgery of GIST
amounts to 2865%

778 patients
18 y
Localized and
primary GIST
KIT-positive
tumors 3 cm
Complete surgical
resection
Placebo for 1 y
Imatinib
400 mg/d for 1 y
Imatinib
400/800 mg/d
713 patients
randomized
Imatinib
400 mg/d
DeMatteo RP, et al. Lancet. 2009;37(9669)3:1097-1104.
Phase 3 ACOSOG Z9001: Trial Schema

Endpoints:

Primary: Recurrence-free survival
Secondary: Overall survival, safety

33
At time of
recurrence
At time of
recurrence
Abbreviations: CI, confidence interval; HR, hazard ratio.
a
All randomized patients were included in the analysis; recurrence-free survival was defined as the time from patient
registration to the development of tumor recurrence or death from any cause. Intention-to-treat analyses were done for
recurrence-free survival (ie, analyzed patients by randomized group).
Adapted from DeMatteo RP, et al. Lancet. 2009;373(9669):1097-1104.
Recurrence-Free Survival
a
HR = 0.35 (95% CI = 0.22, 0.53); P < .0001
100
90
80
70
60
50
40
30
20
10
0
R
e
c
u
r
r
e
n
c
e
-
F
r
e
e

a
n
d

A
l
i
v
e
,

%

0 6 12 18 24 30
Time, mo
36 42 48
Imatinib
Placebo
359
354
30
70
Total Events
Median follow-up: 19.7 mo
34
Size 10 cm
Size 3 and < 6 cm Size 6 and < 10 cm
Recurrence-Free Survival (Tumor Size)
Imatinib adjuvant therapy results
in significantly longer RFS in each
of the tumor size categories
compared with placebo
100
90
80
70
60
50
40
30
20
10
0
R
e
c
u
r
r
e
n
c
e
-
F
r
e
e

a
n
d

A
l
i
v
e
,

%

0 6 12 18 24 30 36 42 48
100
90
80
70
60
50
40
30
20
10
0
R
e
c
u
r
r
e
n
c
e
-
F
r
e
e

a
n
d

A
l
i
v
e
,

%

0 6 12 18 24 30 36 42 48
Imatinib, n = 143
Placebo, n = 149
HR = 0.23 (95% CI = 0.07, 0.79); P = .011
Imatinib, n = 93
Placebo, n = 86
HR = 0.29 (95% CI = 0.16, 0.55); P < .001
Time, mo
Time, mo
100
90
80
70
60
50
40
30
20
10
0
R
e
c
u
r
r
e
n
c
e
-
F
r
e
e

a
n
d

A
l
i
v
e
,

%

0 6 12 18 24 30 36 42 48
Time, mo
Imatinib, n = 123
Placebo, n = 119
HR = 0.50 (95% CI = 0.25, 0.98); P = .041
Abbreviations: CI, confidence interval; HR, hazard ratio; RFS, recurrence-free survival.
Adapted from DeMatteo RP, et al. Lancet. 2009;373(9669):1097-1104.
35
Follow-up
Follow-up
Phase 3 SSGXVIII: Study Design
Randomized
1:1
Imatinib
12 mo
400 patients
KIT-positive
histologically
confirmed GIST
High
recurrence risk
according to
modified NIH
consensus
criteria


Endpoints:

Primary: Recurrence-free survival
Secondary: Overall survival, safety

Imatinib
36 mo
Abbreviation: NIH, National Institutes of Health.
Data from Joensuu H, et al. JAMA. 2012;307(12):1265-1272.

Key Elements:

Patient stratification:
R0 resection, no tumor rupture
R1 resection OR tumor rupture

36
HR = 0.46 (95% CI = 0.32, 0.65); P < .0001
SSGXVIII: Recurrence-Free Survival
(ITT)
Abbreviations: CI, confidence interval; HR, hazard ratio; ITT, intent to treat.
Adapted from Joensuu H, et al. JAMA. 2012;307(12):1265-1272.
60.1%
47.9%
86.6%
65.6%
36 mo, n = 198
12 mo, n = 199
0 1 2 3 4 5 6
0
20
40
60
80
100
Median follow-up,
54 mo
Time, y
R
e
c
u
r
r
e
n
c
e
-
F
r
e
e

a
n
d

A
l
i
v
e
,

%

37