Rachel PatelRadu Reit

Taylor Guffey

Harry Han

Shelby Hassberger

Daniel Kim

Lauren Morgan

Elizabeth Morris

Pancreatic Cancer

◦ Fourth highest cancer deaths

◦ 35,240/42,450 people died in 2009

◦ Survival <1% after 5 years

http://www.cumc.columbia.edu/dept/cs/pancreas/ed_cancer_basics.html

Data to acquire◦CA19-9 Sensitivity◦Best current tests◦Future methods◦Demographics

Criteria◦Sensitivity/Specificity◦Cost◦Stage of Detection ◦Invasiveness◦Identify Age Group

Sensitivity Specificity

Avg Cost/Perso

n

Stage of Detectio

n

Invasiveness

EUS/FNA 95%2 98%2 $3,515 T17 3

EUS 95%2 93%2 $1,111 T17 3

CA-494 90%10 94%10 $225 T110 2

DR-70 90%5*** 93%5*** $100 T15 2

Ultrasound 90%1 90%1 $200 T26 1

CA19-9 88% 85% $129 T111 2

Spyglass 100%3 77%3 $617 T13 3

PET 90%2 81%2 $2,000 M112 2

MRI 89%2 77%2 $2,500 T213 1

CT 83%4 75%4 $2,200 T214 1

ERCP 80%9 61%9 $1,346 T315 3

MRCP 77%8 65%8 $1,145 T215 11Campbell 1988, 2Santo 2004, 4Park 2009, 3Fishman 2009, 5Kerber 2004, 6Berlolto 2007, 7Gress 1999, 8 Hänninen 2005, 9 Scheiman 2001, 10Friess, 11Pezzilli 1995, 12Berberat 1999, 13Ramsay 2004, 14Floer 2005, 15Andersson 2004 *** specific for 3

gastrointestinal cancers

DR70 Biomarker

CA-494

EUS

EUS/FNA

(+)(+)

(+)

Confirmed Pancreatic Cancer

(+)

Testing Population

Highly sensitive◦ DR 70: 90% Sensitive

93% Specific ◦ CA 494: 90% Sensitive

94% Specific

Affordable: ◦ $225 CA 494◦ $100 DR 70

DR 70 Positives◦ 33% Prevalence

DR70 Biomarker

CA-494

EUS

EUS/FNA

(+)(+)

(+)

Confirmed Pancreatic Cancer

(+)

Testing Populatio

n

Moderate cost ◦ $1,100

High Sensitivity◦ 95% Sensitive◦ 93% Specific

Images masses

Helmstaedter 2008

EUS

EUS/FNA

(+)(+)

(+)

Confirmed Pancreatic Cancer

(+)

CA-494DR70

Testing Populatio

n

Testing Populatio

n

Greatest Invasiveness ◦ Biopsy

Sensitive◦ 95% Sensitive◦ 98% Specific

Confirms diagnosisEUS

EUS/FNA

(+)(+)

(+)

Confirmed Pancreatic Cancer

(+)

CA-494DR70

http://www.psychiatrictimes.com/display/article/10165/110108?pageNumber=1&verify=0

10,000,000

EUS/FNA

EUS

DR70 Biomark

erCA-494

(+)(+)

(+)

TP: 6,434FP: 1,154TN: 9,991,709FN: 703

Sensitivity: 90.15%Specificity: 99.99%PPV: 84.79%NPV: 99.99%

TN = Previous FalsePositives * Specificity

TP = Previous TruePositives * Sensitivity

FP = Previous False Positives - TN

FN = Previous True Positives - TP

91.68% subjected to blood test◦ $325 total cost

0.6% spends >$2,000◦ 1 of 11 detected

Stage of Elimination in Strategy

Population Eliminated

DR70/CA-494 9,168,386

EUS 767,127

EUS/FNA 64,487

Sensitivity Specificity

Avg Cost/

Person

Stage of Detectio

n

Invasiveness

Our Strategy

90.15% 99.99% $431 T1 3

EUS/FNA 95%2 98%2 $3,515 T1 3

EUS 95%2 93%2 $1,111 T1 3

CA-494 90% 94% $225 T1 2

DR-70 90%5 93%5 $100 T1 2

Ultrasound 90%1 90%1 $200 > T1 1

CA19-9 88% 85% $129 T1 2

Spyglass 100%3 77%3 $617 T1 3

PET 90%2 81%2 $2,000 M1 2

MRI 89%2 77%2 $2,500 T2 1

CT 83%4 75%4 $2,200 T2 1

ERCP 80% 61% $1,346 > T2 3

MRCP 77% 65% $1,145 T2 1*** specific for 3 gastrointestinal cancers

PAM4 Marker◦ PAM4 antibody detects for MUC1 protein in

pancreas◦ PAM4 Activity shown by imaging

4 hours after injection up to 7 days

◦ MUC1 protein specific to cancerous organs◦ Test in developmental stage

Gold 2007,2008

Screening Frequency◦ Suggested Population Screened

50+ Family history Smoking Obesity

◦ Additional Screening Smoking and Obesity Annual testing

PAM4 antibody method ◦ Decreased invasiveness◦ Increased resolution and accuracy of detection

Yeo 2009

Number of Patients (%)

Characteristics

Overall

TOTAL 27,828

Age at Diagnosis

Mean Age 68.9

<50 6.7%

50-69 42%

>70 51.3%National Cancer Institute’s Surveillance Epidemiology and end results data from 1992-2002

Andersson, R., C. E. Vagianos, et al. (2004). "Preoperative staging and evaluation of resectability in pancreatic ductal adenocarcinoma." HPB 6(1): 5-12.

Berberat, P., H. Friess, et al. (1999). "Diagnosis and Staging of Pancreatic Cancer by Positron Emission Tomography." World Journal of Surgery 23(9): 882-887.

Bertolotto, M., M. D’Onofrio, et al. (2007). "Ultrasonography of the pancreas. 3. Doppler imaging." Abdominal Imaging 32(2): 161-170.

Campbell, J. P. and S. R. Wilson (1988). "Pancreatic neoplasms: how useful is evaluation with US?" Radiology 167(2): 341-344.

Fishman, D. S., P. R. Tarnasky, et al. (2009). "Management of pancreaticobiliary disease using a new intra-ductal endoscope: The Texas experience." World Journal of Gastroenterology 15(11): 1353-1358.

Floer, M., V. Hlouschek, et al. (2005). "“Pancreatic lesion” outside the pancreas: Value of endoscopic ultrasound." Scandinavian Journal of Gastroenterology 40(4): 482-485.

Friess, H., M. B¸chler, et al. (1993). "CA 494†-†a new tumor marker for the diagnosis of pancreatic cancer." International Journal of Cancer 53(5): 759-763.

Gold, D. V., D. M. Goldenberg, et al. (2008). "A novel bispecific, trivalent antibody construct for targeting pancreatic carcinoma." Cancer Research 68(12): 4819-4826.

Gold, D. V., Z. Karanjawala, et al. (2007). "PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma." Clinical Cancer Research: An Official Journal Of The American Association For Cancer Research 13(24): 7380-7387.

Gress, F. G., R. H. Hawes, et al. (1999). "Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience." Gastrointestinal Endoscopy 50(6): 786-791.

H. S. Park, J. M. Lee, H. K. Choi, S. H. Hong, J. K. Han, and B. I. Choi, "Preoperative evaluation of pancreatic cancer: comparison of gadolinium-enhanced dynamic MRI with MR cholangiopancreatography versus MDCT," Journal Of Magnetic Resonance Imaging: JMRI, vol. 30, pp. 586-595, 2009.

Hänninen, E. L., J. Ricke, et al. (2005). "Magnetic Resonance Cholangiopancreatography: Image Quality, Ductal Morphology, and Value of Additional T2‐ and T1‐weighted Sequences for the Assessment of Suspected Pancreatic Cancer." Acta Radiologica 46(2): 117-125.

Helmstaedter, L. and J. F. Riemann (2008). "Pancreatic cancer--EUS and early diagnosis." Langenbeck's Archives Of Surgery / Deutsche Gesellschaft Für Chirurgie 393(6): 923-927.

Kerber A, T. J., Herrlinger K, Zgouras D, Caspary WF, Braden B. (2004). "The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation study." Aliment Pharmacol Ther. 20(9): 983-987.

Pezzilli, R., P. Billi, et al. (1995). "Serum CA 242 in Pancreatic Cancer. Comparison with CA 19-9 and CEA." Ital J Gastroenterol 27(6): 296-299.

Ramsay, D., M. Marshall, et al. (2004). "Identification and staging of pancreatic tumours using computed tomography, endoscopic ultrasound and mangafodipir trisodium-enhanced magnetic resonance imaging." Australasian Radiology 48(2): 154-161.

Santo, E. (2004). "Pancreatic Cancer Imaging: Which Method? " Journal Of The Pancreas 5(4): 253-257 Scheiman, J. M., R. C. Carlos, et al. (2001). "Can endoscopic ultrasound or magnetic

resonance cholangiopancreatography replace ERCP in patients with suspected biliary disease? A prospective trial and cost analysis." The American Journal of Gastroenterology 96(10): 2900-2904.

Yeo, T. P., R. H. Hruban, et al. (2009). "Assessment of "gene-environment" interaction in cases of familial and sporadic pancreatic cancer." Journal Of Gastrointestinal Surgery: Official Journal Of The Society For Surgery Of The Alimentary Tract 13(8): 1487-1494.