Transcript Uncommon complications of Ivor Lweis oeophagectomy

Pre-operative Imatinib for
metastatic, recurrent and locally
advanced GISTs
E. Efthimiou, S Mudan
On behalf of the Sarcoma Group
The Royal Marsden Hospital
Incidence
• Gastrointestinal Stromal Tumours GIST
are the most common mesenchymal
tumours of the gastrointestinal tract.
• The incidence is 15 to 20 cases per million
population per year for symptomatic and
clinically detected GIST.
Kindblom, LG et al : Ann Oncol 2002: 13 (Suppl 5):157, 2002.
Organ distribution
Stomach - 70%
Small bowel - 20%
Colorectum, oesophagus, EGIST - 10%.
Omental GIST
Gastric GIST
Gastric GIST
Gastric GIST
Background
• Surgical resection is feasible in
approximately two thirds of patients with
primary non-metastatic disease.
• Approximately half of these patients
eventually develop intra-peritoneal
recurrence or liver metastases.
• The 5- and 10-year survival after curative
resection is 32% to 78% and 19% to 63%,
respectively.
Roberts PJ,et al Eur J Cancer 2002
Lehnet T, et al Ann Chir Gynaecol 2003
Background
• Imatinib is the effective therapy for
metastatic and inoperable GIST.
• A sufficient down staging may allow
surgical resection either with a curative
intent before or at the time of resistance.
Background
• Stable disease rate 30%
• Partial response rate 50%
• Complete response rate 2%.
Patients
• Twenty five cases of locally advanced
primary, recurrent or metastatic GIST
treated preoperatively with Imatinib were
identified from the sarcoma database in
our Unit.
Design
• Sex, race, age at presentation.
• Site of primary tumour and extent of
disease at presentation.
• Dose of Imatinib prior to the operation,
side effects and duration of treatment.
• Maximal tumour diameter and radiological
response.
• Surgical procedure and completeness of
resection.
• Disease status at last follow-up.
Gender
12 male
13 female
Site of primary tumour origin
Gastric greater curve
Gastric lesser curve
0GJ
rectum
Small bowel
8
10
4
2
1
State of response at the time of
surgery
progression
stable
Progressive
disease
5
Stable
disease
20
Histological Grade
High
Intermediate
1
Low
4
20
Pathologic response to Imatinib
No resection 3
No response 2
Partial response 20
Resection
R1
OC
R0
R2
3pts (12%)
6 pts (24%)
3pts (12%)
13 pts (52%)
Recurent/metastatic
7
Locally advanced
18
•
Number ofpatients
•
Male/Female
1/6
•
Median age at diagnosis
48
63
•
Side effects of Imatinib
Diarrhea
Rash
Neutropenia
Peri-orbital oedema
Indigestion
Pleural effusion
Ankle edema
7
1
1
1
4
2
1
-
11
3
5
4
2
3
•
•
Pre Imatinib diameter
Post imatinib diameter
6.7cm
6.6cm
11/7
14.1cm
9.8cm
Recurent/metastatic
•
•
•
•
Pathological response
Partial response
No response
Tumour not resected
•
Median Glivec Duration
•
•
•
•
•
•
Median Overall survival
Disease status at follow up
Disease free
Liver and peritoneal metastases
Primary disease
Dead
5
2
27 months (range 6-62)
46 months (range 20-77)
2
3
2
Locally advanced
15
3
9 months (range 5-32)
9.5 months (range 5-52)
11
4
2
1
Postoperative survival in
metastatic and recurrent versus
locally advanced GISTS
Locally advanced GISTs
Reccurent/metastatic
GISTS 71%
94%
Survival and site of origin of
primary GIST
77%
Gastric GISTs
90%
33%
Survival and extent of resection
50%
Survival in R2 resections
Survival and pathologic response
90%
90%
50%
50%
Post operative survival and status
of response at operation
90%
80%
Overall survival
Median 32monts (range 8-77 months)
Summary 1
• 2/7 of the metastatic and recurrent GIST
patients achieved macroscopic clearance .
• 5/7 alive after a median period of 46
months (range 20-77)
Summary 2
•
94% of the locally advanced group are
alive at median FU 9.5 months
(range 5-52).
•
Median duration on Imatinib was 27
months for recurrent and metastatic
GIST versus 9 months for locally
advanced.
Summary 3
• R2 resection was associated with worse
survival.
• Absence of pathological response was
associated with 50% survival versus 90%
for partial response.
Conclusions
• Recurrent /metastatic patients required
longer duration of treatment before
surgery and were less likely to achieve the
goal of complete macroscopic clearance.
• Hence the survival was inferior to the
locally advanced group.