1. The clinical role of PET scanning in GIST Seattle 2007 The clinical role of PET scanning in a consecutive series of GIST patients Department of Surgery Netherlands Cancer Institute - Antoni van Leeuwenhoek ziekenhuis Amsterdam The Netherlands Frits van Coevorden & Lester van Ravenswade

2. The clinical role of PET scanning in GIST Seattle 2007 The metabolic activity in GastroIntestinal Stromal Tumors has become of interest in this era of targeted therapyThe metabolic activity in GastroIntestinal Stromal Tumors has become of interest in this era of targeted therapy Positron Emission Tomography is the imaging modality to assess metabolic activity in tumorsPositron Emission Tomography is the imaging modality to assess metabolic activity in tumors

3. The clinical role of PET scanning in GIST Seattle 2007 The metabolic activity in GastroIntestinal Stromal Tumors has become of interest in this new Imatinib eraThe metabolic activity in GastroIntestinal Stromal Tumors has become of interest in this new Imatinib era Positron Emission Tomography is the imaging modality to assess metabolic activity in tumorsPositron Emission Tomography is the imaging modality to assess metabolic activity in tumors PET imaging may reveal the metastatic character of tumorsPET imaging may reveal the metastatic character of tumors Comparing PET activity before and after the start of TKI’s may provide useful information in assessing the response to drug treatmentComparing PET activity before and after the start of TKI’s may provide useful information in assessing the response to drug treatment

4. The clinical role of PET scanning in GIST Seattle 2007 In a consecutive series of 98 evaluable patients seen in the Netherlands Cancer Institute between 2000 – 2007 our GIST database was reviewed with focus on the use of PET scanningIn a consecutive series of 98 evaluable patients seen in the Netherlands Cancer Institute between 2000 – 2007 our GIST database was reviewed with focus on the use of PET scanning The indication for PET imaging was classified as:The indication for PET imaging was classified as: Diagnostic to evaluate the primary tumorDiagnostic to evaluate the primary tumor Diagnostic to evaluate metastatic diseaseDiagnostic to evaluate metastatic disease

5. The clinical role of PET scanning in GIST Seattle 2007 In a consecutive series of 98 evaluable patients seen in the Netherlands Cancer Institute between 2000 – 2007 our GIST database was reviewed with focus on the use of PET scanningIn a consecutive series of 98 evaluable patients seen in the Netherlands Cancer Institute between 2000 – 2007 our GIST database was reviewed with focus on the use of PET scanning The indication for PET imaging was classified as:The indication for PET imaging was classified as: Diagnostic to evaluate a primary tumorDiagnostic to evaluate a primary tumor Diagnostic to evaluate metastatic diseaseDiagnostic to evaluate metastatic disease Diagnostic tool to prove or exclude recurrent or residual disease after previous surgeryDiagnostic tool to prove or exclude recurrent or residual disease after previous surgery Response assessment of drug treatmentResponse assessment of drug treatment

6. The clinical role of PET scanning in GIST Seattle 2007 Methods We reviewed all files and PET -CT studiesWe reviewed all files and PET -CT studies Classified PET imaging as:Classified PET imaging as: diagnostic onlydiagnostic only diagnostic and used for response evaluationdiagnostic and used for response evaluation

7. The clinical role of PET scanning in GIST Seattle 2007 Methods We reviewed all files and PET -CT studiesWe reviewed all files and PET -CT studies Classified PET imaging as:Classified PET imaging as: diagnostic onlydiagnostic only diagnostic and used for response evaluationdiagnostic and used for response evaluation Correlated the outcome to the associated CT scanCorrelated the outcome to the associated CT scan Classified the comparison results as:Classified the comparison results as: Conformal or DiscrepantConformal or Discrepant

8. The clinical role of PET scanning in GIST Seattle 2007 Methods We reviewed all files and PET -CT studiesWe reviewed all files and PET -CT studies Classified PET imaging as:Classified PET imaging as: diagnostic onlydiagnostic only diagnostic and used for response evaluationdiagnostic and used for response evaluation Correlated the outcome to the associated CT scanCorrelated the outcome to the associated CT scan Classified the comparison results as:Classified the comparison results as: Conformal or DiscrepantConformal or Discrepant Correlated the results to the clinical course of the patient with follow upCorrelated the results to the clinical course of the patient with follow up

9. The clinical role of PET scanning in GIST Seattle 2007 Results (1) the data here presented are an update of those in abstract 934the data here presented are an update of those in abstract 934 98 evaluable patients98 evaluable patients 45 patients had one or more PET scans45 patients had one or more PET scans 4 scans as tool to search for residual or possible recurrent disease after surgery:4 scans as tool to search for residual or possible recurrent disease after surgery: All were negative, as was the clinical and CT correlate In 41 patients PET was supposed to show activityIn 41 patients PET was supposed to show activity

10. The clinical role of PET scanning in GIST Seattle 2007 Results (2) PET was false negative in 9 / 45 patients (20 %)PET was false negative in 9 / 45 patients (20 %) 3 in active primary or local recurrent disease3 in active primary or local recurrent disease 6 in metastatic hepatic or peritoneal disease6 in metastatic hepatic or peritoneal disease

11. The clinical role of PET scanning in GIST Seattle 2007 Results (2) PET was false negative in 9 / 45 patients (20 %)PET was false negative in 9 / 45 patients (20 %) 3 in active primary or local recurrent disease3 in active primary or local recurrent disease 45 yr female 6 cm bilobar endogastric Gist 45 yr female 6 cm bilobar endogastric Gist

12. The clinical role of PET scanning in GIST Seattle 2007 Results (2) PET was false negative in 9 / 45 patients (20%)PET was false negative in 9 / 45 patients (20%) 3 in active primary or local recurrent disease3 in active primary or local recurrent disease 51 yr male 10 cm small curvature gastric Gist 51 yr male 10 cm small curvature gastric Gist 50% vital after 1 yr Imatinib

13. The clinical role of PET scanning in GIST Seattle 2007 Results (3) PET was false negative in 9 / 45 patients (20 %)PET was false negative in 9 / 45 patients (20 %) PET was true negative in 4 patients (post surgery controls)PET was true negative in 4 patients (post surgery controls) PET was true positive in 32 patientsPET was true positive in 32 patients …. so 80 % correlation to CT scan and Clinic !! …. so 80 % correlation to CT scan and Clinic !!

14. The clinical role of PET scanning in GIST Seattle 2007 Results (3) PET was false negative in 9 / 45 patients (20 %)PET was false negative in 9 / 45 patients (20 %) PET was true negative in 4 patients (post surgery controls)PET was true negative in 4 patients (post surgery controls) PET was true positive in 32 patientsPET was true positive in 32 patients Repeat PET used for response assessment in 23 patientsRepeat PET used for response assessment in 23 patients

15. The clinical role of PET scanning in GIST Seattle 2007 Results (4) Repeat PET for response assessment in 23 patientsRepeat PET for response assessment in 23 patients 19 patients PET confirmed good response19 patients PET confirmed good response 3 unchanged PET activity confirmed active SD on CT 3 unchanged PET activity confirmed active SD on CT …. so if 1 st PET shows disease activity …. so if 1 st PET shows disease activity 95 % correlation to CT scan and Clinic !!

16. The clinical role of PET scanning in GIST Seattle 2007 Results (4) Repeat PET for response assessment in 23 patientsRepeat PET for response assessment in 23 patients 19 patients confirmed good response19 patients confirmed good response 3 unchanged PET activity confirmed active SD on CT 3 unchanged PET activity confirmed active SD on CT 1 discrepancy 1 discrepancy

17. The clinical role of PET scanning in GIST Seattle 2007 Case presented at CTOS 2006 in Venice 33 yr male33 yr male dec 2005 resection of high grade small bowel GISTdec 2005 resection of high grade small bowel GIST randomized in 62024 to control grouprandomized in 62024 to control group

18. The clinical role of PET scanning in GIST Seattle 2007 Case presented at CTOS 2006 in Venice 33 yr male33 yr male dec 2005 resection of high grade small bowel GISTdec 2005 resection of high grade small bowel GIST randomized in 62024 to control grouprandomized in 62024 to control group aug 2006: peritoneal recurrenceaug 2006: peritoneal recurrence Start Imatinib 400 mgStart Imatinib 400 mg

19. The clinical role of PET scanning in GIST Seattle 2007 Case presented at CTOS 2006 in Venice

20. The clinical role of PET scanning in GIST Seattle 2007 August 2006: Start (neoadjuvant)Imatinib 400 mg October 2006: effect ??? After Glivec Before Glivec After Glivec Progression ? So he went for surgery Or response ?

21. The clinical role of PET scanning in GIST Seattle 2007 Before Glivec After Glivec Bad message: At pathology the PET negative tumor more than 90% vital GIST

22. The clinical role of PET scanning in GIST Seattle 2007 Bad message: At pathology the PET negative tumor more than 90% vital GIST Good message: Exon 9 mutation Now 1 year later on 800 mg Imatinib: NO ACTIVE DISEASE So maybe PET did predict a favourable outcome very early ??

23. The clinical role of PET scanning in GIST Seattle 2007 PET positive initial scan False PET negative scan True PET negative scan ALL 45 pat NED125421 Alive with inactive disease 9211 Alive with active disease 314 Dead of disease 819 Survival related to PET scanning

24. The clinical role of PET scanning in GIST Seattle 2007 Beneficial PET response No change or progressive disease at PET ALL NED or inactive disease 1313 Alive with active disease 55 Dead of disease 325 PET response correlated to outcome at FU

25. The clinical role of PET scanning in GIST Seattle 2007 Conclusions PET had a 80 % correlation to active GIST but PET was false negative in 20 % If PET is positive: 95% correct response correlationIf PET is positive: 95% correct response correlation No change or PD at response assessment predicts a poor outcomeNo change or PD at response assessment predicts a poor outcome

26. The clinical role of PET scanning in GIST Seattle 2007 Thank you