??GIST?????

1
??GIST?????
?????????? ???
2
???????GIST
2009.2.12
2009.2.12
??
????,30?,2009.2????GIST??4?????????? ??CT???????
??3?,???14.5cm
3
???????GIST

• ????
• ??2005?1?(26?),????????????????????,??????????
  ,?????
• ??????GIST,??8cm,???5-10/50HPF
• CD117, CD34

4
????????????
????? ????(CM) ????/ 50HPF ??????
?? lt2.0 5 ????
? 2.1-5.0 5 ????
? 2.1-5.0 gt5 ?
? lt5.0 6-10 ????
? 5.1-10.0 5 ?
? ?? ?? ????
? gt10 ?? ????
? ?? gt10 ????
? gt5 gt5 ????
? 2.1-5.0 gt5 ??
? 5.1-10.0 5 ??
v
Joesuu. Human Pathology. Vol.39,No.10.2008. pp.
1416-1419
5
?????GIST????
6
?????????GIST?????
??????57?? SD???PR???????
84???????
Blanke CD et al. J Clin Oncol. 2008 26 626-632
7
??????????GIST

• ????85
• ???GIST??????18-24????36-57?
• 400mg/d??????????,??????

1.Blanke CD, et al. J Clin Oncol 2008 26(4)
620625 2.Gold JS, et al. Ann Surg Oncol. 2007
Jan14(1)134-42. 3.Blanke CD, et al. J Clin
Oncol. 2008 Feb 126(4)626-32.
8
2?
5?
2009.4.17
2009.2.12
2009.9.22
???? 400mg/d
9
2009.4.17
2009.9.22
IM??7?
IM??2?
10
????????

• ??????????(RECIST)
• ????????gt20--??(PD)
• GIST?????????--Choi
• ????????10?/?????(HU)??15???,??TTP???????RECIS
  T??,?PET SUVmax???

Choi H. et al. J Clin Oncol. 2007, 1753-60.
11
Choi?????GIST?????
?? ??
CR ?????? ?????
PR CT????????10 ?????(HU)??15 ????? ???????????
SD ???CR?PR?PD?? ????????????
PD ??????10,????????PR?? ?????? ?????????????????
Choi H. et al. J Clin Oncol. 2007, 1753-60.
12
Choi?????GIST?????

• ??GIST?Choi??,??CT?????15,??????(PR)
• ????????,?????????????,????????,????????????,?????
  ????????

13
????????????
???????, ??????????
??????, ??????????
????
??????, ????
14
2009.10.20
2009.10.28
15
????

• ????8???,??IM400mg/?
• ????????????
• KIT?PDGFRA???--???
• ????CT??,???????

16
???????

• 2010.5.4??,?????????

2005.1??
2009. 2.12
2009. 9.22
2009. 10.20
2010. 05.04
??GIST, ??,??
??IM400mg/d??
IM??7?,PR, ????
??
??,??CR
17
?????????IM??????
B2222??
Heinrich MC et al. J Clin Oncol 2003 4342-49
18
?????IM??????
EORTC62005??
Percent
KIT Exon 9(n 58)
KIT Exon 11(n 248)
Wild Type(n 52)
Debiec-Rychter M et al. Eur J Cancer.
20061093-103.
19
???????IM?????
B2222--??????IM??????

• KIT 11????????????KIT 9????????(??OS????vs192?vs36
  ?)
• ????IM??????

OS?()
??(?)
Blanke CD, Demetri GD,et al. Proc Am Soc Clin
Oncol. 200624526s. Abstract 9528
20
???????IM?????
Progression-Free Survival
Overall Survival
EORTC62005??,PFS?OS???, ????9???IM????,??11????
Debiec-Rychter M et al. Eur J Cancer.
2006421093-1103.
21
???????IM?????
Overall Survival
Progression-Free Survival
S0033????,???EORTC62005?? EORTC62005?S0033???????
??????B2222????, ????????11??
Heinrich MC et al J Clin Oncol 2008 265360-67.
22
???????
??PFS 45?
KIT?PDGFRA?????????PFS???
73????GIST????????????,????11?????????,????9??
23
????(?)

• ??????????????
• ????????,??PFS?7?
• ??73????GIST???,????11?????????
• ???????????????????????????

24
????(?) ??????????GIST??????
Chaudhry UI, DeMatteo RP. Hematol Oncol Clin N Am
2009
Ye YJ, et al. EJSO 2009
25
GIST?????????????    

• TKI??????????GIST????????????
• TKI??????????????????(????????)???

?GIST???????????,??????????????????,TKI??????TK
I
Chaudhry UI, DeMatteo RP. Hematol Oncol Clin N Am
2009
Ye YJ, et al. EJSO 2009
26
????????????GIST

• TKI??GIST????
• ?????lt5
• IM????14,502?????,gt904?????
• ??TKI????PFS?2124?,??OS???90?

??GIST????????????
1.Blanke CD, et al. J Clin Oncol.
2008626-32. 2.Reichardt P, et al. ASCO Meeting
Abstracts 2008 10548  3.Demetri GD, et al.
Lancet. 20061329-38.
27
?????????????????????????GIST???III???7
?????? ????III?????
????III???????7 ????????400mg?gt400mg??????????,H
R???0.27?0.33
7 . Demetri G, et. al. Effi cacy and safety of
sunitinib in patients with advanced
gastrointestinal stromal tumour after failure of
imatinib a randomised controlled trial Lancet
2006 3681329-38
28

?????????????????
???????????????????GIST???????????????????????9
400 mg/d ??OS?90?(n351) gt400 mg/d
??OS?70?(n368)
???IM??
???????OS????75?
N1117
?????????400 mg/d???OS?90?,??S0033??81.4?
9. P. Reichardt, et al. Detailed analysis of
survival and safety with sunitinib (SU) in a
worldwide treatment-use trial of patients with
advanced GIST. 2008 ASCO Annual Meeting, abs
10548
29
???????????,??????????PR, SD,PFS?OS
????(IM)800 mg vs ????(SU)
IM S0033??12(n98) IM 62005??12(n133) SU III???7,8 (n361) SU??????9 (n1117) SU????????10 (n60)
PR() 7 (5/77) 2 (3/133) 7 (14/207) NR 12(7/60)
SD() 32 (25/77) 27 (36/133) 58 (120/207) NR 67(40/60)
TTP(?) NR NR 27.3 41 NR
PFS(?) 16 11.6 24.6 NR 34
OS(?) 60 NR 73.9 75 90 107
30
????????????GIST

• ????
• ??????????????
• ???????????????
• ???????????????

1. Eisenberg BL, et al. J Surg Oncol.42-7.
2. Raut CP, et al. J Clin Oncol 2006 232531.
3. DeMatteo RP, et al. Ann Surg. 2007347-52.
4. Raut CP, et al. Ann Surg Oncol. 2010407-15.

31
????????????GIST
????
?????
????
?????
?????
?????
N69
PFS
OS
???GIST???????????, ?????????????PFS?OS???????
Raut CP, et al. J Clin Oncol 2006 232531.
32
????????????GIST
????, N20
????, N20
????, N13
????, N13
????, N7
????, N7
PFS
N40
OS
?????????????PFS?OS?????
DeMatteo RP, et al. Ann Surg. 2007347-52.
33
??????????????GIST

• ?????????????
• 2007.6-2010.2,24????GIST,???????????
• ??????
• (1) ????PRSD
• (2)????????????,??????
• (3)????????????????,??????????????

34
??????????????GIST

• ????
• ????????,
• IM?? 128?(??5?)
• SU?? 714?(??10?)
• ?????????
• ????,
• ???????(?????lt1cm)
• ?????(????1cm)

35
??????????????GIST
????/ ????? N17
???? N13
Plt0.001
P0.006
????? N6
????? N4
????? N6
P0.238
?????????,?????????????
36
??????????????GIST

• ?????????????
• ?????????,???????????????PFS?????(P0.005)
• ???????????
• ???????????GIST??????????????,????????
• ???GIST????????????

Raut CP, et al. J Clin Oncol 2006
232531. DeMatteo RP, et al. Ann Surg. 2007347-52
37
??????????????????
?????? OS PFS PFS
?????? ????? (P) ?????(P) ?????(P)
?? 0.318 0.727
?? 0.921 0.671
???? 0.597 0.527
????? 0.413 0.087
?????????/?? 0.175 0.223
??????
?????? OS PFS PFS
?????? ????? (P) ?????(P) ?????(P)
????(gt1cm) lt0.001 0.052
????? 0.006 0.051
??ECOG?? lt0.001 0.001
??? 0.020 0.002
??TKI???? lt0.001 lt0.001 0.005
???? 0.074 0.077
???? 0.865 0.331
38
??????????????GIST

• ???????????????,????????,?????,???????
• ????????????????????,?????
• ??????????12.5,????????
• ???????GIST???????????????,???????54
• ????????,????????,????????????

1. Raut CP, et al. J Clin Oncol 2006 232531.
2. DeMatteo RP, et al. Ann Surg. 2007347-52
3. Raut CP, et al. Ann Surg Oncol. 2010407-15.

39
??????????????GIST

• ????????????GIST??????
• ???TKI?????????????
• ???????????????
• ??????????????????,?????????????????,??????????

40
? ? !