170707469 Gist Workshop

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 criteria1

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 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.

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 Survivala

HR = 0.35 (95% CI = 0.22, 0.53); P < .0001 100

90

80

70

60

50

40

30

20

10

0

Re

curr

en

ce-F

ree

and

Aliv

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 Rec

urr

ence

-Fre

e an

d A

live

, %

0 6 12 18 24 30 36 42 48

100 90 80 70 60 50 40

30 20 10

0 Rec

urr

ence

-Fre

e an

d A

live,

%

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


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 Rec

urr

ence

-Fre

e an

d A

live,

%

0 6 12 18 24 30 36 42 48 Time, mo


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

Re

curr

en

ce-F

ree

an

d A

live

, %

37

170707469 Gist Workshop

Documents

Transcript of 170707469 Gist Workshop