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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 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 http://www.cumc.columbia.edu/dept/cs/pancreas/ed_cancer_basics.html
Introduction • Data to acquire • CA19-9 Sensitivity • Best current tests • Future methods • Demographics
Introduction • Criteria • Sensitivity/Specificity • Cost • Stage of Detection • Invasiveness • Identify Age Group
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
Strategy Testing Population DR70 Biomarker CA-494 (+) (+) EUS (+) EUS/FNA (+) Confirmed Pancreatic Cancer
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
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
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
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
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
Cost and Comfort • 91.68% subjected to blood test • $325 total cost • 0.6%spends >$2,000 • 1 of 11 detected
Updated Quantitative Analysis *** specific for 3 gastrointestinal cancers
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
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
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.
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.