Application of PositronEmission Tomography ( PET ) in Colorectal Cancer

Dr Chan Wai KeungDepartment of SurgeryRuttonjee and Tang Shiu Kin Hospitals

• What is PET

• Liver metastasis

• Extrahepatic metastasis

• Elevated CEA

• Local recurrence

• Monitor resposnse to therapy

PET - Background

• Positron emission tomography ( PET ) in use for 20 years

• Initially for research purposes

• Clinical application since 90s

• Wide clinical uses: carcinomas, melanoma, lymphoma,

epilepsy, dementia, cerebrovascular disease, coronary

artery disease and others

PET - Basic Principles

• A PET tracer is administered and takes part in physiological processes

• Different concentrations at different locations

• The PET scanner detects signals

• The resulting images showed functional information

Anhilation

PET - Basic Principles

• Metabolically active cells can take up the tracer

• Enhanced activity seen in brain, skeletal muscle, bowel, myocardium, genitourinary tract, thyroid and others

• “Functional imaging”help detection at earlier stage than cross sectional imaging

18 Fluoro-2-deoxy-D-glucose ( 18FDG )

• A glucose analogue developed in 1970s

• Tumor cells have increased metabolism and glucolysis and hence increased uptake of 18FDG

• Uptake not exclusive to tumor cells

• Good accumulation in tumor cells, long half-life, ease of availability

Glucose

18FDG

a

18FDG

Standard Uptake Value ( SUV )

• The most common parameter

• Related to the injected dose per body mass

• Correct emission scan with an attenuation scan

• Higher in tumor

• Sensitivity : TP / ( TP + FN )

• Specificity : TN / ( FP + TN )

• Positive predictive value : TP / ( TP + FP )

• Negative predictive value : TN / ( TN + FN )

Pre-operative Diagnosis

• A study of 48 patients with established or suspicious

diagnoses of colorectal cancer

• PET scan detected all lesions

• Positive and negative predective values of 90% and 100%

Abdel-Nabi H., Radiology, 1998

Lymph Node Detection

• CT scan and MRI - sensitivity of 22 to 48%, accuracy of 40 to 65% for colonic cancer

• For rectal cancer, sensitivity of 73% and accuracy of 70%

Thoeni R.F., Radiol Clin North Am, 1997

• Sensitivity of lymph node detection by PET of 29%

Abdel-Nabi H., Radiology, 1998

Colorectal Liver Metastasis

• 25% have liver metastasis at diagnosis

• Another 20% will have liver metastasis

• 30 to 40% have 5-years survival after hepatectomy

• Patient selection - anatomical resectability and no extra-

hepatic involvement

PET in Liver Metastasis

• Superiority of PET over CT in detecting liver metastasis

not eastablished

• No adequate spatial information about metastases

• The main role into detect extrahepatic involvement

Arulampalam T.H.A., 2003

a

Para-caval LNPara-aortic LNLiver

Extrahepatic Disease in Liver Metastasis

• 51 patients analyzed for resection for colorectal liver

metastasis

• PET result in 20% change of management because of

unexpected extrahepatic involvement

Ruers T.J., J Clin Oncol, 2002

PET showed identical lesions to CT scan

Spinal metastasis

• Spinal metastasis detected by PET but not by CT

• Spinal cord compression 3 months after hepatectomy

Hepatic and Extrahepatic Lesions

PET and Liver Resectability

• 43 patients for hepatectomy for liver metastasis

• 6 patients spared of surgery due to extrahepatic disease

• Hepatectomy in 35 out of 37 patients

• 95% resectability rate of hepatic metastasis with PET in

addition to other imaging techniques

• At 3 years 77% overall and 40% disease free survival

Strasberg S.M., Ann Surg, 2000

Overall Survival

Disease Free Survival

Elevated CEA

• Investigated by conventional imaging modalities and colonoscopy - still some have negative imaging

• CEA directed laparotomy: low resectability rate of 44 to 58% because of unexpected presence of extensive disease

Minton J.P., Cancer, 1985

Martin E.W.Jr., Am J Surg, 1979

Elevated CEA

• PET for 32 patients with elevated CEA

• Histological diagnosis, serial CT and clinical follow-up as standards

• Sensitivity - 90%, specificity 92%

• Positive predicitive value 95%

• Negative predicitive value 85%

Valk P.E., Arch Surg, 1999

Elevated CEA with Normal Imaging

• 22 patients with elevated CEA and normal conventional imaging

• 17 recurrent lesions found - histological confirmation in 7, recurrence on follow up in 8, false positive in 2

• No recurrence in those with negative PET

Flanagan F.L., Ann Surg,

1999

Metastatic Disease - PET vs CT

• 41 patients had laparotomy for metastatic colorectal cancer

• All have pre-op PET and CT

• Sensitivity : liver ( 100% vs 69% ), extraheaptic ( 90% vs 52% ), abdomen ( 87% vs 61%), pelvis ( 87% vs 61%)

Johnson K., Dis Colon Rectum,

2001

Local Recurrent Disease - PET vs CT

• 70 patients with suspected locally recurrent colorectal cancer

• PET compared with CT / Colonoscopy

• Sensitivity : 90% vs 71%

• PPV and NPV: PET - 88% and 92%

CT - 79% and 79%

Whiteford M.H., Dis Colon Rectum, 2000

Arulampalam T.H.A., 2003

Monitoring Therapy of Colorectal Cancer

• Response to chemotherapy and regional therapy

monitored by PET

• FDG uptake decreased in responding lesions

• To separate responsders from non-responders

• Residual uptake help to guide further therapy

Pre Chemotherapy

Post Chemotherapy

Limitation of PET

• Detectability depends on size and degree of uptake

• False -ve in small lesion and necrotic lesions

• Low sensitivity in mucinous adenocarcinoma

• False +ve in inflammed tissue

• Usual FDG activity at gastrointestinal tract

Impact on Management

• Early detection of abnormal tissue metabolism

• Detection of tumor at usual and unexpected sites

• Avoid unnecessary surgery

• Allow earlier treatment by diagnosing recurrence earlier

• Monitor treatment response

• PET is a power imaging modality but its use needs to be refined

Conclusion

• PET is a functional imaging technique

• It detects hepatic and extrahepatic lesions, and help to

avoid unnecessay surgery by detecting extrahepatic

disease

• It detects recurrent disease in patients with elevated CEA

and negative imaging

• Its helps to monitor treatment and guide further treatment

Thank You !