Preoperative Imatinib for metastatic, recurrent and locally advanced GISTs

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Pre-operative Imatinib for metastatic, recurrent
and locally advanced GISTs

• E. Efthimiou, S Mudan
• On behalf of the Sarcoma Group
• The Royal Marsden Hospital

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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.

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Organ distribution

• Stomach - 70
• Small bowel - 20
• Colorectum, oesophagus, EGIST - 10.

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• Omental GIST

• Gastric GIST

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• Gastric GIST

• Gastric GIST

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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

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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.

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Background

• Stable disease rate 30
• Partial response rate 50
• Complete response rate 2.

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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.

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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.

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Gender
13 female
12 male
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Site of primary tumour origin
0GJ
13
State of response at the time of
surgery
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Histological Grade
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Pathologic response to Imatinib
No resection 3
No response 2
Partial response 20
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Resection
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• 
  Recurent/metastatic
  Locally advanced
• Number ofpatients
  7
  18
• Male/Female
  1/6
  11/7
• Median age at diagnosis
  48
  63
• Side effects of Imatinib
  7
  11
• Diarrhea
  1
  3
• Rash
  1
  5
• Neutropenia
  1
  -
• Peri-orbital oedema
  4
  4
• Indigestion
  2
  2
  
• Pleural effusion
  1
  -
• Ankle edema
  -
  3
• Pre Imatinib diameter
  6.7cm
  14.1cm
• Post imatinib diameter
  6.6cm
  9.8cm

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• 
  
  Recurent/metastatic Locally
  advanced
• Pathological response
• Partial response
  5
  15
• No response
  2
  -
• Tumour not resected
  -
  3
•  
• Median Glivec Duration
  27 months (range 6-62)
  9 months (range 5-32)
•  Median Overall survival 
  46 months (range 20-77)
  9.5 months (range 5-52)
• Disease status at follow up
• Disease free
  2
  11
• Liver and peritoneal metastases
  3
  4
• Primary disease
  -
  2
• Dead
  2
  1

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Postoperative survival in metastatic and
recurrent versus locally advanced GISTS
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Survival and site of origin of primary GIST
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Gastric GISTs
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Survival and extent of resection
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Survival in R2 resections
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Survival and pathologic response
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Post operative survival and status of response at
operation
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Overall survival
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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)

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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.

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Summary 3

• R2 resection was associated with worse survival.
• Absence of pathological response was associated
  with 50 survival versus 90 for partial response.

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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.