1. Rachel Patel Radu Reit Taylor Guffey Harry Han Shelby Hassberger Daniel Kim Lauren Morgan Elizabeth Morris

2.  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

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

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

5. SensitivitySpecificityAvg Cost/Person Stage of Detection Invasiveness EUS/FNA95% 2 98% 2 $3,515T1 7 3 EUS95% 2 93% 2 $1,111T1 7 3 CA-49490% 10 94% 10 $225T1 10 2 DR-7090% 5*** 93% 5*** $100T1 5 2 Ultrasound90% 1 $200T2 6 1 CA19-988%85%$129T1 11 2 Spyglass100% 3 77% 3 $617T1 3 3 PET90% 2 81% 2 $2,000M1 12 2 MRI89% 2 77% 2 $2,500T2 13 1 CT83% 4 75% 4 $2,200T2 14 1 ERCP80% 9 61% 9 $1,346T3 15 3 MRCP77% 8 65% 8 $1,145T2 15 1 1 Campbell 1988, 2 Santo 2004, 4 Park 2009, 3 Fishman 2009, 5 Kerber 2004, 6 Berlolto 2007, 7 Gress 1999, 8 Hänninen 2005, 9 Scheiman 2001, 10 Friess, 11 Pezzilli 1995, 12 Berberat 1999, 13 Ramsay 2004, 14 Floer 2005, 15 Andersson 2004 *** specific for 3 gastrointestinal cancers

6. DR70 BiomarkerCA-494 EUS EUS/FNA (+) Confirmed Pancreatic Cancer (+) Testing Population

7.  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 BiomarkerCA-494 EUS EUS/FNA (+) Confirmed Pancreatic Cancer (+) Testing Population

8.  Moderate cost ◦ $1,100  High Sensitivity ◦ 95% Sensitive ◦ 93% Specific  Images masses Helmstaedter 2008 EUS EUS/FNA (+) Confirmed Pancreatic Cancer (+) CA-494DR70 Testing Population

9.  Greatest Invasiveness ◦ Biopsy  Sensitive ◦ 95% Sensitive ◦ 98% Specific  Confirms diagnosis EUS EUS/FNA (+) Confirmed Pancreatic Cancer (+) CA-494DR70 http://www.psychiatrictimes.com/display/article/ 10165/110108?pageNumber=1&verify=0

10. 10,000,000 EUS/FNA EUS DR70 Biomarker CA-494 9,288,780 TN 10,859 TP 1206 (402 PC) FN 699,155 FP (+) 9,396,260 TN 3,581 TP 398 FN 599,761 FP 766,771 TN 6,773 TP 356 FN 57,714 FP 56,560 TN 6,434 TP 339 FN 1,154 FP TP: 6,434 FP: 1,154 TN: 9,991,709 FN: 703 Sensitivity: 90.15% Specificity: 99.99% PPV: 84.79% NPV: 99.99%

11.  9,396,260 TN  3,581 TP  398 FN  599,761 FP TN = Previous False Positives * Specificity TP = Previous True Positives * Sensitivity FP = Previous False Positives - TN FN = Previous True Positives - TP

12.  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-4949,168,386 EUS767,127 EUS/FNA64,487

13. SensitivitySpecificityAvg Cost/ Person Stage of Detection Invasiveness Our Strategy 90.15%99.99%$431T13 EUS/FNA95% 2 98% 2 $3,515T13 EUS95% 2 93% 2 $1,111T13 CA-49490%94%$225T12 DR-7090% 5 93% 5 $100T12 Ultrasound90% 1 $200> T11 CA19-988%85%$129T12 Spyglass100% 3 77% 3 $617T13 PET90% 2 81% 2 $2,000M12 MRI89% 2 77% 2 $2,500T21 CT83% 4 75% 4 $2,200T21 ERCP80%61%$1,346> T23 MRCP77%65%$1,145T21 *** specific for 3 gastrointestinal cancers

14.  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

15.  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 (%) CharacteristicsOverall TOTAL27,828 Age at Diagnosis Mean Age68.9 <506.7% 50-6942% >7051.3% National Cancer Institute’s Surveillance Epidemiology and end results data from 1992-2002

16.  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). "‚ÄúPancreatic lesion‚Äù 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.

17.  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.