INTESTINAL GIST

WORKSHOP GIST SEMARANG 14 SEPTEMBER 2013

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? postoperative?) 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
NIH consensus criteria1 Tumor size < 2 cm Mitotic index < 5

Low Risk
Tumor size 2-5 cm Mitotic index < 5

Intermediate Risk
Tumor size 5-10 cm Mitotic index < 5 OR Tumor size < 5 cm Mitotic index 6-10

High Risk
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 classification2

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.

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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%

Phase 3 ACOSOG Z9001: Trial Schema

778 patients 18 y Localized and primary GIST KIT-positive tumors 3 cm Complete surgical resection Imatinib
400 mg/d for 1 y

At time of recurrence

Imatinib 400/800 mg/d

713 patients randomized At time of recurrence Imatinib 400 mg/d

Placebo for 1 y

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

DeMatteo RP, et al. Lancet. 2009;37(9669)3:1097-1104. 33

Recurrence-Free Survivala
100 90 Recurrence-Free and Alive, % 80 70 60 50 40 30 20 10 0 0 6 12 18 24 Time, mo
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. Imatinib Placebo Total 359 354 Events 30 70

HR = 0.35 (95% CI = 0.22, 0.53); P < .0001

Median follow-up: 19.7 mo 30 36 42 48

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Recurrence-Free Survival (Tumor Size)

100 90 80 70 60 50 40 30 20 10 0 0
HR = 0.23 (95% CI = 0.07, 0.79); P = .011

Size 3 and < 6 cm

Imatinib, n = 143 Placebo, n = 149 6 12 18 24 30 Time, mo 36 42 48

100 90 80 70 60 50 40 30 20 10 0 0

HR = 0.50 (95% CI = 0.25, 0.98); P = .041

Recurrence-Free and Alive, %

Recurrence-Free and Alive, %

Size 6 and < 10 cm

Imatinib, n = 123 Placebo, n = 119 6 12 18 24 30 Time, mo 36 42 48

24 30 36 42 48 Time, mo Abbreviations: CI, confidence interval; HR, hazard ratio; RFS, recurrence-free survival. Adapted from DeMatteo RP, et al. Lancet. 2009;373(9669):1097-1104.

100 90 80 70 60 50 40 30 20 10 0

Recurrence-Free and Alive, %

HR = 0.29 (95% CI = 0.16, 0.55); P < .001

Size 10 cm
Imatinib, n = 93 Placebo, n = 86 0 6 12 18

Imatinib adjuvant therapy results in significantly longer RFS in each of the tumor size categories compared with placebo

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Phase 3 SSGXVIII: Study Design

400 patients KIT-positive histologically confirmed GIST High recurrence risk according to modified NIH consensus criteria Imatinib 12 mo

Follow-up
Randomized 1:1

Imatinib 36 mo

Follow-up
Endpoints: Primary: Recurrence-free survival Secondary: Overall survival, safety
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

SSGXVIII: Recurrence-Free Survival (ITT)

100 HR = 0.46 (95% CI = 0.32, 0.65); P < .0001 86.6% 80 65.6% 60 40 20
Median follow-up, 54 mo

Recurrence-Free and Alive, %

60.1% 47.9%

36 mo, n = 198
12 mo, n = 199

6
37

Time, y
Abbreviations: CI, confidence interval; HR, hazard ratio; ITT, intent to treat. Adapted from Joensuu H, et al. JAMA. 2012;307(12):1265-1272.