The clinical role of PET scanning in a consecutive series of GIST patients

The clinical role of PET scanning in GISTThe clinical role of PET scanning in GIST

Seattle Seattle 20072007

The clinical role of PET scanning in a consecutive series of GIST patients

Department of SurgeryDepartment of Surgery

Netherlands Cancer InstituteNetherlands Cancer Institute - - Antoni van Leeuwenhoek ziekenhuisAntoni van Leeuwenhoek ziekenhuis Amsterdam The NetherlandsAmsterdam The Netherlands

Frits van CoevordenFrits van Coevorden & &

Lester van RavenswadeLester van Ravenswade



• The metabolic activity in GastroIntestinal Stromal Tumors The metabolic activity in GastroIntestinal Stromal Tumors has become of interest in this era of targeted therapyhas become of interest in this era of targeted therapy

• Positron Emission Tomography is Positron Emission Tomography is thethe imaging modality to imaging modality to assess metabolic activity in tumorsassess metabolic activity in tumors



• The metabolic activity in GastroIntestinal Stromal Tumors has The metabolic activity in GastroIntestinal Stromal Tumors has become of interest in this new Imatinib erabecome of interest in this new Imatinib era

• Positron Emission Tomography is Positron Emission Tomography is thethe imaging modality to imaging modality to assess metabolic activity in tumorsassess 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 Comparing PET activity before and after the start of TKI’s may provide useful information in assessing the response to may provide useful information in assessing the response to drug treatmentdrug treatment



• In a consecutive series of 98 evaluable patients seen in the In a consecutive series of 98 evaluable patients seen in the Netherlands Cancer Institute between 2000 – 2007 our GIST Netherlands Cancer Institute between 2000 – 2007 our GIST database was reviewed with focus on the use of PET scanningdatabase 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



• In a consecutive series of 98 evaluable patients seen in the In a consecutive series of 98 evaluable patients seen in the Netherlands Cancer Institute between 2000 – 2007 our GIST Netherlands Cancer Institute between 2000 – 2007 our GIST database was reviewed with focus on the use of PET scanningdatabase 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 Diagnostic tool to prove or exclude recurrent or residual disease after previous surgeryresidual disease after previous surgery

• Response assessment of drug treatmentResponse assessment of drug treatment



MethodsMethods

• 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



MethodsMethods





• 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



MethodsMethods





• 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 Correlated the results to the clinical course of the patient with follow upwith follow up



Results (1)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 4 scans as tool to search for residual or possible recurrent disease after surgery: recurrent disease after surgery:

All were negative, as was the clinical and CT correlateAll 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




• PET was false negative in PET was false negative in 9 9 //4545 patients (20 %) patients (20 %)

• 33 in active primary or local recurrent disease in active primary or local recurrent disease

• 66 in metastatic hepatic or peritoneal disease in metastatic hepatic or peritoneal disease





• 3 in active primary or local recurrent disease3 in active primary or local recurrent disease

45 yr female45 yr female 6 cm bilobar endogastric Gist 6 cm bilobar endogastric Gist




• PET was false negative in PET was false negative in 9 9 //4545 patients (20%) patients (20%)

• 3 in active primary or local recurrent disease3 in active primary or local recurrent disease

51 yr male51 yr male 10 cm small curvature gastric Gist 10 cm small curvature gastric Gist

50% vital after 1 yr Imatinib50% vital after 1 yr Imatinib





• 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 !!





• 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




• Repeat PET for Repeat PET for response assessment in 23 patientsresponse assessment in 23 patients

• 19 19 patients PET confirmed good response patients PET confirmed good response

• 3 3 unchanged PET activity confirmed active SD on CT unchanged PET activity confirmed active SD on CT

……. . so if 1so if 1stst PET shows disease activity PET shows disease activity

95 %95 % correlation to CT scan and Clinic !! correlation to CT scan and Clinic !!




• Repeat PET for Repeat PET for response assessment in 23 patientsresponse assessment in 23 patients

• 19 19 patients confirmed good response patients confirmed good response

• 3 3 unchanged PET activity confirmed active SD on CTunchanged PET activity confirmed active SD on CT

• 1 1 discrepancydiscrepancy



Case presented at CTOS 2006 in VeniceCase 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




• 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






August 2006: Start (neoadjuvant)Imatinib 400 mgAugust 2006: Start (neoadjuvant)Imatinib 400 mg

October 2006: effect ???October 2006: effect ???After GlivecAfter Glivec

Before Glivec Before Glivec After GlivecAfter Glivec

Progression ?Progression ?

So he went for surgerySo he went for surgery

Or response ?Or response ?



Before Glivec Before Glivec After GlivecAfter Glivec

After GlivecAfter Glivec

Bad message: Bad message:

At pathology the At pathology the PET negative tumor PET negative tumor more than 90% vital GISTmore than 90% vital GIST



Bad message: Bad message:

At pathology the PET negative tumor more than 90% vital GISTAt pathology the PET negative tumor more than 90% vital GIST

Good message: Good message:

Exon 9 mutationExon 9 mutation

Now 1 year later on 800 mg Imatinib: NO ACTIVE DISEASENow 1 year later on 800 mg Imatinib: NO ACTIVE DISEASE

So maybe PET did predict a favourable outcome very So maybe PET did predict a favourable outcome very early ??early ??



PET PET positive positive initial initial scanscan

False False PET PET

negative negative scanscan

True PET True PET negative negative

scanscanALLALL

45 pat45 pat

NEDNED 1212 55 44 2121

Alive withAlive with

inactive diseaseinactive disease99 22 1111

Alive with Alive with active diseaseactive disease

33 11 44

Dead of diseaseDead of disease 88 11 99

Survival related to PET scanningSurvival related to PET scanning



BeneficialBeneficial

PET responsePET response

No change or No change or progressive disease at progressive disease at

PET PET ALLALL

NED or NED or inactive diseaseinactive disease

1313 1313

Alive with Alive with active diseaseactive disease

55 55

Dead of diseaseDead of disease 33 22 55

PET response correlated to outcome at FUPET response correlated to outcome at FU



ConclusionsConclusions

PET had a 80 % correlation to active GIST PET had a 80 % correlation to active GIST

but PET was false negative in 20 %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 No change or PD at response assessment predicts a poor predicts a poor

outcome outcome



Thank youThank you

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The clinical role of PET scanning in a consecutive series of GIST patients