Application of Positron Emission Tomography ( PET ) in Colorectal Cancer Dr Chan Wai Keung

1. Application of Positron Emission Tomography ( PET ) in Colorectal Cancer Dr Chan Wai Keung Department of Surgery Ruttonjee and Tang Shiu Kin Hospitals

2. What is PET • Liver metastasis • Extrahepatic metastasis • Elevated CEA • Local recurrence • Monitor resposnse to therapy

3. 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

7. 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

8. Anhilation

9. 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

10. 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

11. Glucose

12. 18FDG a

13. 18FDG

14. 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

17. Sensitivity : TP / ( TP + FN ) • Specificity : TN / ( FP + TN ) • Positive predictive value : TP / ( TP + FP ) • Negative predictive value : TN / ( TN + FN )

18. 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

19. 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

20. 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

21. 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

22. Arulampalam T.H.A., 2003

23. a Liver Para-aortic LN Para-caval LN

24. 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

25. PET showed identical lesions to CT scan

26. Spinal metastasis • Spinal metastasis detected by PET but not by CT • Spinal cord compression 3 months after hepatectomy

27. Hepatic and Extrahepatic Lesions

28. 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

29. Overall Survival

30. Disease Free Survival

31. 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

32. 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

34. 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

35. 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

37. 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

38. Arulampalam T.H.A., 2003

39. 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

40. Pre Chemotherapy

41. Post Chemotherapy

42. 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

43. 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

44. 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

45. Thank You !