Advances in Nuclear Medicine and Advances in Nuclear Medicine and its Impact on Diagnosis and its Impact on Diagnosis and Management of GI CancersManagement of GI Cancers

Medhat Osman, MD PhDMedhat Osman, MD PhD

Philip Alderson, MDPhilip Alderson, MD

2007 Estimated US Cancer 2007 Estimated US Cancer CasesCases**

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2007.

Men766,860

Women678,060 26%26% BreastBreast

15%15% Lung & bronchusLung & bronchus

11%11% Colon & rectumColon & rectum

6%6% Uterine corpus Uterine corpus

4%4% Non-Hodgkin Non-Hodgkin

lymphoma lymphoma

4%4% Melanoma of skinMelanoma of skin

4% Thyroid4% Thyroid

3%3% OvaryOvary

3%3% KidneyKidney

3%3% LeukemiaLeukemia

21%21% All Other SitesAll Other Sites

ProstateProstate

29%29%

Lung & bronchusLung & bronchus

15%15%

Colon & rectumColon & rectum

10%10%

Urinary bladderUrinary bladder

7%7%

Non-Hodgkin Non-Hodgkin

4% 4%

lymphomalymphoma

Melanoma of skinMelanoma of skin

4%4%

KidneyKidney

4%4%

Leukemia Leukemia

3%3%

Oral cavityOral cavity

3%3%

PancreasPancreas

2%2%

All Other SitesAll Other Sites

19%19%

2007 Estimated US Cancer 2007 Estimated US Cancer DeathsDeaths**

ONS=Other nervous system.Source: American Cancer Society, 2007.

Men289,550

Women270,100 26%26% Lung & bronchusLung & bronchus

15%15% BreastBreast

10%10% Colon & rectumColon & rectum

6%6% PancreasPancreas

6%6% OvaryOvary

4%4% LeukemiaLeukemia

3%3% Non-HodgkinNon-Hodgkin lymphoma lymphoma

3%3% Uterine corpusUterine corpus

2%2% Brain/ONSBrain/ONS

2%2% Liver & intrahepatic Liver & intrahepaticbile ductbile duct

23% All other sites23% All other sites

Lung & bronchusLung & bronchus 31%31%

ProstateProstate 9%9%

Colon & rectum Colon & rectum 9%9%

PancreasPancreas 6%6%

LeukemiaLeukemia 4%4%

Liver & intrahepaticLiver & intrahepatic 4%4%bile ductbile duct

EsophagusEsophagus 4%4%

Urinary bladderUrinary bladder 3% 3%

Non-Hodgkin 3% Non-Hodgkin 3% lymphoma lymphoma

KidneyKidney 3%3%

All other sites 24%All other sites 24%

Lifetime Probability of Developing Lifetime Probability of Developing Cancer, by Site, Women, 2001-2003Cancer, by Site, Women, 2001-2003**

Site Risk

All sites† 1 in 3

Breast 1 in 8

Lung & bronchus 1 in 16

Colon & rectum 1 in 19

Uterine corpus 1 in 40

Non-Hodgkin lymphoma 1 in 55

Ovary 1 in 69

Melanoma 1 in 73

Pancreas 1 in 79

Urinary bladder‡ 1 in 87

Uterine cervix 1 in 138

Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.1.1 Statistical Research and Applications Branch, NCI, 2006. http://srab.cancer.gov/devcan

* For those free of cancer at beginning of age interval. Based on cancer cases diagnosed during 2001 to 2003.

* For those free of cancer at beginning of age interval. Based on cancer cases diagnosed during 2001 to 2003.

Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.1.1 Statistical Research and Applications Branch, NCI, 2006. http://srab.cancer.gov/devcan

Lifetime Probability of Developing Lifetime Probability of Developing Cancer, by Site, Men, 2001-2003Cancer, by Site, Men, 2001-2003**

Site Risk

All sites† 1 in 2

Prostate 1 in 6

Lung and bronchus 1 in 12

Colon and rectum 1 in 17

Urinary bladder‡ 1 in 28

Non-Hodgkin lymphoma 1 in 47

Melanoma 1 in 49

Kidney 1 in 61

Leukemia 1 in 67

Oral Cavity 1 in 72

Stomach 1 in 89

Basic QuestionsBasic Questions

Is it cancer?Is it cancer? Is it localized ?Is it localized ? How to treat?How to treat? Is treatment working?Is treatment working? Is more treatment needed?Is more treatment needed?

Limitations of Anatomic Imaging Limitations of Anatomic Imaging Tumor diagnosisTumor diagnosis Disease stagingDisease staging Therapeutic response & disease recurrenceTherapeutic response & disease recurrence Radiation exposureRadiation exposure

– Annual background: 3 mSv Annual background: 3 mSv – Chest PA : 0.02 mSvChest PA : 0.02 mSv– Screeing Mammogram: 0.4 mSvScreeing Mammogram: 0.4 mSv– CT CT

» Chest: 8-18 mSvChest: 8-18 mSv» Abdomen: 3.5- 25 mSvAbdomen: 3.5- 25 mSv» Pelvis: 3.3-10 mSv Pelvis: 3.3-10 mSv

Mettler FA, et al. Radiology 2008:248 (1):254-263

Benefits of PET ImagingBenefits of PET Imaging

Improved diagnostic specificityImproved diagnostic specificity Improved tumor stagingImproved tumor staging Improved monitoring of response to therapyImproved monitoring of response to therapy Improved monitoring of disease recurrenceImproved monitoring of disease recurrence

Limitations of PET ImagingLimitations of PET Imaging

False-positiveFalse-positive False-negativeFalse-negative Limited spatial resolutionLimited spatial resolution Inability to pinpoint tumor locationInability to pinpoint tumor location Two hours per study!Two hours per study!

Positron Emission TomographyPositron Emission Tomography

Advantages of PET-CT ScannerAdvantages of PET-CT Scanner

Whole-body staging in one examWhole-body staging in one exam Nearly simultaneous acquisition of PET and Nearly simultaneous acquisition of PET and

CT imagesCT images Improved anatomic lesion localizationImproved anatomic lesion localization Shorter PET image acquisitionShorter PET image acquisition Lower radiation exposureLower radiation exposure

– Whole body PET/CT at SLU: < 20 mSv Whole body PET/CT at SLU: < 20 mSv – Chest, abdomen and pelvic CT: 14.8-53 mSvChest, abdomen and pelvic CT: 14.8-53 mSv

COLORECTAL CARCINOMACOLORECTAL CARCINOMA Initial Diagnosis Initial Diagnosis

Sensitivity: 85%Sensitivity: 85% Specificity: 67%Specificity: 67%

Facey K, et al. NHS. R&D Programme: July 2004

Colorectal Liver MetastasesColorectal Liver Metastases

Wiering B, et al. Cancer 2005:104:2658-2670

SensitivitySensitivity SpecificitySpecificity

PETPET 88%88% 96%96%

ceCTceCT 83%83% 84%84%

Colorectal Liver Metastases; Colorectal Liver Metastases; on a per-lesion basison a per-lesion basis

Bipat S, et al. Radiology. 2005:273:123-131

SensitivitySensitivity

PETPET 76%76%

ceCTceCT 64%64%

MRI (1.5-T)MRI (1.5-T) 64%64%

Extrahepatic LesionsExtrahepatic Lesions

Wiering B, et al. Cancer. 2005:104:2658-2670

SensitivitySensitivity SpecificitySpecificity

PETPET 92%92% 95%95%

ceCTceCT 61%61% 91%91%

PET Changes Management and Improves PET Changes Management and Improves Prognostic Stratification in Patients with Prognostic Stratification in Patients with

Recurrent Colorectal Cancer: Results of a Recurrent Colorectal Cancer: Results of a Multicenter Prospective StudyMulticenter Prospective Study

65.6% of patients with residual structural lesion 65.6% of patients with residual structural lesion suggestive of recurrencesuggestive of recurrence

49% of patients with potentially resectable pulmonary 49% of patients with potentially resectable pulmonary or hepatic metastasesor hepatic metastases

Scott AM, et al. J Nuc Med. 2008;49:1451-1457

63-yo with prostate ca, s/p 63-yo with prostate ca, s/p prostatectomy prostatectomy

Pre XRT colonoscopy Pre XRT colonoscopy revealed rectal massrevealed rectal mass

Biopsy: rectal cancer Biopsy: rectal cancer Abd ceCT: no metsAbd ceCT: no mets PET/CT for stagingPET/CT for staging

ESOPHAGEAL CANCERESOPHAGEAL CANCER Initial Diagnosis Initial Diagnosis

PET is more accurate than conventional PET is more accurate than conventional imaging modalitiesimaging modalities

The overall incremental value of PET The overall incremental value of PET compared to CT with regard to staging compared to CT with regard to staging accuracy was 14%accuracy was 14%

Kato H, et al. Cancer. 2005:103:148-156

Detection of Metastases:Detection of Metastases:

LocalLocal– Sensitivity: 52%Sensitivity: 52%– Specificity: 84%Specificity: 84%

Distant Distant – Sensitivity: 67%Sensitivity: 67%– Specificity: 97%Specificity: 97%

Facey K, et al. NHS. R&D Programme: July 2004Von Westreenen NH, et al. J Clin Oncol. 2004;22:3850-3812

65-yo M with history of 65-yo M with history of laryngeal ca, s/p XRTlaryngeal ca, s/p XRT

Recent dx of esophageal ca Recent dx of esophageal ca ceCT: no metsceCT: no mets PET/CT for stagingPET/CT for staging

PANCREATIC CANCER;PANCREATIC CANCER;Differentiating Benign From Differentiating Benign From

Malignant LesionsMalignant Lesions

Orlando LA, et al. Aliment Pharmacol Ther. 2004;20:1063-1070

SensitivitySensitivity SpecificitySpecificity

PET/CTPET/CT 71% - 100%71% - 100% 53% - 100%53% - 100%

ceCTceCT 53% - 100%53% - 100% 0% - 100%0% - 100%

54-yo M with jaundice54-yo M with jaundice ceCT: pancreatic mass with ceCT: pancreatic mass with

no metastasesno metastases Biopsy: pancreatic CaBiopsy: pancreatic Ca PET/CT for stagingPET/CT for staging

Male, age 66Male, age 66 Former smokerFormer smoker New LUL massNew LUL mass PET/CT for diagnosis and PET/CT for diagnosis and

stagingstaging

ADVANCESADVANCES

New scannersNew scanners New tracersNew tracers Open coverageOpen coverage

GEMINI TFGEMINI TF PET/CT scanner PET/CT scanner with TruFlight technologywith TruFlight technology

A B C D E

“WHOLE-BODY” FOV VARIATIONS

S Huston, M M Osman, SNM05S Huston, M M Osman, SNM05

Added Value of True Whole-Body Added Value of True Whole-Body Over Limited Whole-Body FDG Over Limited Whole-Body FDG

PET/CT in Cancer PatientsPET/CT in Cancer Patients

ResultsResults

20/ 500 (4%) of patients had new, previously 20/ 500 (4%) of patients had new, previously unidentified cancerous lesions outside LWB FOVunidentified cancerous lesions outside LWB FOV

Detection of malignancy outside LWB resulted in Detection of malignancy outside LWB resulted in changed in management in 13 (65%) and staging in changed in management in 13 (65%) and staging in 11 (55%) of those 20 patients11 (55%) of those 20 patients

Of those 20, 5/500 (1%) patients had their only Of those 20, 5/500 (1%) patients had their only malignant lesion outside the LWB FOVmalignant lesion outside the LWB FOV

Osman MM, et al. SNM. 2006

PET/CTPET/CT

PET/MR

F-18 FLT PETF-18 FLT PET

Imaging Gastric Cancer with PET Imaging Gastric Cancer with PET and the Radiotracers and the Radiotracers 1818F-FLT and F-FLT and 1818F-FDG: A Comparative AnalysisF-FDG: A Comparative Analysis

Hermann, et al. J Nuc Med. 2007;48:1945-1950

Sensitivity and Uptake of Sensitivity and Uptake of 1818F-FLT &F-FLT &1818F-FDG in F-FDG in Gastric CancerGastric Cancer

Imaging gastric cancer with proliferation Imaging gastric cancer with proliferation marker marker 1818F-FLT is feasibleF-FLT is feasible

1818F-FLT was more sensitive than F-FLT was more sensitive than 1818F-FDG, F-FDG, especially in tumors presenting with no/low especially in tumors presenting with no/low 1818F-FDG uptakeF-FDG uptake

Detection of HCC Using Detection of HCC Using 1111C-Choline: C-Choline: Comparison withComparison with1818F-FDGF-FDG

ceCT 11C-Choline 18F-FDG

Detection of HCC:Detection of HCC:1818C-Choline vsC-Choline vs1818F-FDG F-FDG

1111C-Choline had a better detection rate compared had a better detection rate compared to to 1818F-FDG for a moderately differentiated HCC F-FDG for a moderately differentiated HCC lesions but not for poorly differentiated lesionslesions but not for poorly differentiated lesions

1818F-FDG produce the opposite results 1111C-Choline is a potential tracer to complement is a potential tracer to complement1818F-F-

FDG in the detection of HCC lesions FDG in the detection of HCC lesions

Yamamoto Y, et al. J Nuc Med. 2008;49:1245-1248

PET/CT: THE MOST IMPORTNAT PET/CT: THE MOST IMPORTNAT CANCER IMAGING MODALITY CANCER IMAGING MODALITY

NOPR 08 UPDATENOPR 08 UPDATE >1500 facilities contributed data from >23,000 patients>1500 facilities contributed data from >23,000 patients FDG-PET changed treatment in 36.5% FDG-PET changed treatment in 36.5%

JCO, published online March 24, 2008