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Screening for Pancreatic Cancer

Screening for Pancreatic Cancer. Rachel Patel Radu Reit Taylor Guffey Harry Han Shelby Hassberger Daniel Kim Lauren Morgan Elizabeth Morris. Introduction. Pancreatic Cancer Fourth highest cancer deaths 35,240/42,450 people died in 2009 Survival <1% after 5 years.

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Screening for Pancreatic Cancer

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

  2. Introduction • 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. Introduction • Data to acquire • CA19-9 Sensitivity • Best current tests • Future methods • Demographics

  4. Introduction • Criteria • Sensitivity/Specificity • Cost • Stage of Detection • Invasiveness • Identify Age Group

  5. Quantitative Analysis 1Campbell 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

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

  7. DR70 and CA-494 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

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

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

  10. Statistical Analysis 10,000,000 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 (+) (+) TP: 6,434 FP: 1,154 TN: 9,991,709 FN: 703 766,771 TN 6,773 TP 356 FN 57,714 FP Sensitivity: 90.15% Specificity: 99.99% PPV: 84.79% NPV: 99.99% EUS (+) 56,560 TN 6,434 TP 339 FN 1,154 FP EUS/FNA

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

  12. Cost and Comfort • 91.68% subjected to blood test • $325 total cost • 0.6%spends >$2,000 • 1 of 11 detected

  13. Updated Quantitative Analysis *** specific for 3 gastrointestinal cancers

  14. Future Tests • 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. Recommendations • 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 National Cancer Institute’s Surveillance Epidemiology and end results data from 1992-2002 Yeo 2009

  16. Additional Citations • Andersson, R., C. E. Vagianos, et al. (2004). "Preoperative staging and evaluation of resectability in pancreatic ductaladenocarcinoma." HPB6(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 Imaging32(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). "‚ÄúPancreaticlesion‚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. Additional Citations (Continued) • 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 Endoscopy50(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." ActaRadiologica 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 Chirurgie393(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 PharmacolTher. 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 Gastroenterol27(6): 296-299. • Ramsay, D., M. Marshall, et al. (2004). "Identification and staging of pancreatic tumours using computed tomography, endoscopic ultrasound and mangafodipirtrisodium-enhanced magnetic resonance imaging." Australasian Radiology48(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.

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