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

This study explores the role of pre-operative Imatinib in metastatic, recurrent, and locally advanced GISTs, assessing its effectiveness in downstaging tumors and influencing surgical intervention. Results highlight varying survival rates and outcomes based on treatment response and disease stage.

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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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