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

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.

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

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  1. Pre-operative Imatinib for metastatic, recurrent and locally advanced GISTs E. Efthimiou, S Mudan On behalf of the Sarcoma Group The Royal Marsden Hospital

  2. 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.

  3. Organ distribution Stomach - 70% Small bowel - 20% Colorectum, oesophagus, EGIST - 10%.

  4. Omental GIST Gastric GIST

  5. Gastric GIST Gastric GIST

  6. 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 ChirGynaecol 2003

  7. 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.

  8. Background • Stable disease rate 30% • Partial response rate 50% • Complete response rate 2%.

  9. 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.

  10. 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.

  11. Gender 12 male 13 female

  12. Gastric greater curve Gastric lesser curve rectum Small bowel 8 10 4 1 2 Site of primary tumour origin 0GJ

  13. progression stable Progressive disease 5 Stable disease 20 State of response at the time of surgery

  14. High Intermediate 1 Low 4 20 Histological Grade

  15. Pathologic response to Imatinib No resection 3 No response 2 Partial response 20

  16. Resection R1 OC R0 3pts (12%) R2 6 pts (24%) 3pts (12%) 13 pts (52%)

  17. 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

  18. 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

  19. Postoperative survival in metastatic and recurrent versus locally advanced GISTS Locally advanced GISTs 94% Reccurent/metastatic GISTS 71%

  20. Survival and site of origin of primary GIST 77%

  21. Gastric GISTs 90% 33%

  22. 50% Survival and extent of resection

  23. Survival in R2 resections

  24. Survival and pathologic response 90% 90% 50% 50%

  25. Post operative survival and status of response at operation 90% 80%

  26. Overall survival Median 32monts (range 8-77 months)

  27. 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)

  28. 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.

  29. Summary 3 • R2 resection was associated with worse survival. • Absence of pathological response was associated with 50% survival versus 90% for partial response.

  30. 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.

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