Barry W. Feig, M.D.Robert S. Benjamin, M.D.
The SARCOMA Center
The Connective Tissue Oncology Society
Surgical Treatment of GIST post Imatinib
QuickTime™ and aTIFF (LZW) decompressor
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0 1 2 3 4 5 6 7 8 9 10
1.00
0.80
0.60
0.40
0.20
0.00
YEARS
PROPORTION
vs
vsvs p = 0.64
p = 0.002p = 0.002
TOTAL FAIL
9326396
12376697
Chemotherapy + Surgery CRChemotherapy CRPartial ResponseStable Disease
SOFT TISSUE SARCOMAS 1971-1977SOFT TISSUE SARCOMAS 1971-1977
Time to Progression - Distant Time to Progression - Distant MetastasesMetastases
GIST: Management of Resistance
• If the majority of tumor is controlled by imatinib mesylate, then continue therapy
• Dose escalation up to 800-1000 mg/d as tolerated
• Surgical resection of progressing sites if possible
• Other trials
Demetri et al. JNCCN. 2004;21(suppl 1):S1.
RADIOGRAPHIC RESPONSE TO IMATINIB IN RECURRENT / METASTATIC GIST (N=35)
Response category
Complete resection
(n=11)
Incomplete resection
(n=24)
Complete response 0 (0%) 0 (0%)
Partial response 10 (91%) 1 (4%) Continuous regression 2 0
Initial regression then stable 8 1
Stable disease 0 (0%) 0 (0%)
Progressive disease 1 (9%) 23 (96%) Initial regression then progression 0 18
Continuous progression 1 5
TIME OF SURGERY IN IMATINIB RESPONSIVE RECURRENT / METASTATIC GIST
COMPLETE RESECTION
(N=11)
INCOMPLETE RESECTION
(N=18)
Median (months) 10.0 18.0 23.7
SURGERY
SURGERY
PROGRESSION
P=0.04
FOLLOW-UP RECURRENT / METASTATIC GIST (N=35)
Follow-up
Complete resection
(n=11)
Incomplete resection
(n=24)P
Since imatinib initiation
(months)39.1
(28.7 – 48.1)
36.2
(11.6 – 48.0)
0.10
Postoperative (months) 30.7
(0.2 - 35.3)
11.8
(0.8 – 30.9)
<0.001
GIST Surgery: Randomized Study
• Surgery vs No Surgery
• Surgery at maximum response vs Surgery at first evidence of relapse.
TIME OF SURGERY IN IMATINIB RESPONSIVE RECURRENT / METASTATIC GIST
COMPLETE RESECTION
(N=11)
INCOMPLETE RESECTION
(N=18)
Median (months) 10.0 18.0 23.7
SURGERY
SURGERY
PROGRESSION
P=0.04
TIME OF SURGERY IN IMATINIB RESPONSIVE RECURRENT / METASTATIC GIST
R
A
N
D
O
M
I
Z
E
Months (estimate) 10 18 20
EARLY SURGERY
DELAYEDSURGERY
PROGRESSION
GIST Surgery: Endpoints• Time to Progression from start of imatinib
– If no difference, then surgery does not have a role
– If TTP longer with early surgery, then surgery is adding
• Survival– If no difference, delayed surgery is preferable
(not all will need it).– If survival better with early surgery, it is better
to do at that time.
Barry W. Feig, M.D.Robert S. Benjamin, M.D.
The SARCOMA Center
The Connective Tissue Oncology Society
Surgical Treatment of GIST post Imatinib
QuickTime™ and aTIFF (LZW) decompressor
are needed to see this picture.