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 ( 18 FDG ) A glucose analogue developed in 1970s Tumor cells have increased metabolism and glucolysis and hence increased uptake of 18 FDG Uptake not exclusive to tumor cells Good accumulation in tumor cells, long half-life, ease of availability

11. Glucose

12. 18 FDG a

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 Para-caval LNPara-aortic LNLiver

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 !