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Cited by 224Pancreatic and Hepatic Oncology ResearchMathematical Biology Tumor GrowthGlobal Cancer Incidence and Screening

Time to progression of pancreatic ductal adenocarcinoma from low-to-high tumour stages

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Yu, Jun, Blackford, Amanda L, dal Molin, Marco, Wolfgang, Christopher L, Goggins, Michael·2015·Gut
DOI 10.1136/gutjnl-2014-308653PMC PMC4520782
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Abstract

Objective: Although pancreatic ductal adenocarcinoma is considered a rapidly progressive disease, mathematical models estimate that it takes many years for an initiating pancreatic cancer cell to grow into an advanced stage cancer. In order to estimate the time it takes for a pancreatic cancer to progress through different tumor, node, metastasis (TNM) stages, we compared the mean age of patients with pancreatic cancers of different sizes and stages. Design: Patient age, tumour size, stage and demographic information were analysed for 13 131 patients with pancreatic ductal adenocarcinoma entered into the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. Multiple linear regression models for age were generated, adjusting for patient ethnicity, gender, tumour location and neoplastic grades. Results: African-American ethnicity and male gender were associated with an earlier age at diagnosis. Patients with stage I cancers (mean age 64.8 years) were on average 1.3 adjusted years younger at diagnosis than those with stage IV cancers (p=0.001). Among patients without distant metastases, those with T1 stage cancers were on average 1.06 and 1.19 adjusted years younger, respectively, than patients with T3 or T4 cancers (p=0.03 for both). Among patients with stage IIB cancers, those with T1/T2 cancers were 0.79 adjusted years younger than those with T3 cancers (p=0.06). There was no significant difference in the mean adjusted age of patients with stage IA versus stage IB cancers. Conclusions: These results are consistent with the hypothesis that once pancreatic ductal adenocarcinomas become detectable clinically progression from low-stage to advanced-stage disease is rapid.

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  1. [2]Ludwig E, Olson SH, Bayuga S, et al Feasibility and yield of screening in relatives from familial pancreatic cancer families. Am J Gastroenterol 2011; 106: 946– 54. 10.1038/ajg.2011.65 21468009 PMC3683863 · DOI
  2. [3]Verna EC, Hwang C, Stevens PD, et al Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics. Clin Cancer Res 2010; 16: 5028– 37. 10.1158/1078-0432.CCR-09-3209 20876795 · DOI · Paper page
  3. [4]Langer P, Kann PH, Fendrich V, et al Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer. Gut 2009; 58: 1410– 18. 10.1136/gut.2008.171611 19470496 · DOI
  4. [5]Canto MI, Goggins M, Hruban RH, et al Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 2006; 4: 766– 81. 10.1016/j.cgh.2006.02.005 16682259 · DOI · Paper page
  5. [6]Canto MI, Goggins M, Yeo CJ, et al Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol 2004; 2: 606– 21. 10.1016/S1542-3565(04)00244-7 15224285 · DOI · Paper page
  6. [7]Brentnall T, Bronner M, Byrd D, et al Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 1999; 131: 247– 55. 10.7326/0003-4819-131-4-199908170-00003 10454945 · DOI · Paper page
  7. [8]Poley JW, Kluijt I, Gouma DJ, et al The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. Am J Gastroenterol 2009; 104: 2175– 81. 10.1038/ajg.2009.276 19491823 · DOI · Paper page
  8. [10]Brune K, Abe T, Canto M, et al Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer. Am J Surg Pathol 2006; 30: 1067– 76. 16931950 PMC2746409
  9. [13]Norris AL, Roberts NJ, Jones S, et al Familial and sporadic pancreatic cancer share the same molecular pathogenesis. Fam Cancer 2014 In press. PMC4357548 25240578
  10. [14]Lennon AM, Wolfgang CL, Canto MI, et al The early detection of pancreatic cancer: what will it take to diagnose and treat curable pancreatic neoplasia? Cancer Res 2014; 74: 3381– 9. 10.1158/0008-5472.CAN-14-0734 24924775 PMC4085574 · DOI
  11. [15]Kanda M, Sadakari Y, Borges M, et al Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clin Gastroenterol Hepatol 2013; 11: 719– 30. 10.1016/j.cgh.2012.11.016 23200980 PMC3600161 · DOI · Paper page
  12. [16]Khashab MA, Yong E, Lennon AM, et al EUS is still superior to multidetector computerized tomography for detection of pancreatic neuroendocrine tumors. Gastrointest Endosc 2011; 73: 691– 6. 10.1016/j.gie.2010.08.030 21067742 · DOI
  13. [18]Ferrone CR, Pieretti-Vanmarcke R, Bloom JP, et al Pancreatic ductal adenocarcinoma: long-term survival does not equal cure. Surgery 2012; 152: S43– 9. 10.1016/j.surg.2012.05.020 22763261 PMC3806092 · DOI
  14. [19]Winter JM, Cameron JL, Campbell KA, et al 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg 2006; 10: 1199– 210; discussion 1210–1191 10.1016/j.gassur.2006.08.018 17114007 · DOI
  15. [20]de Jong MC, Li F, Cameron JL, et al Re-evaluating the impact of tumor size on survival following pancreaticoduodenectomy for pancreatic adenocarcinoma. J Surg Oncol 2011; 103: 656– 62. 10.1002/jso.21883 21283994 PMC3578317 · DOI
  16. [21]Honda O, Johkoh T, Sekiguchi J, et al Doubling time of lung cancer determined using three-dimensional volumetric software: comparison of squamous cell carcinoma and adenocarcinoma. Lung Cancer 2009; 66: 211– 17. 10.1016/j.lungcan.2009.01.018 19250697 · DOI
  17. [22]Nishida K, Kaneko T, Yoneda M, et al Doubling time of serum CA 19-9 in the clinical course of patients with pancreatic cancer and its significant association with prognosis. J Surg Oncol 1999; 71: 140– 6. 10.1002/(SICI)1096-9098(199907)71:3<140::AID-JSO2>3.0.CO;2-T 10404129 · DOI
  18. [23]Gerlee P The model muddle: in search of tumor growth laws. Cancer Res 2013; 73: 2407– 11. 10.1158/0008-5472.CAN-12-4355 23393201 · DOI
  19. [24]Edwards BK, Brown ML, Wingo PA, et al Annual report to the nation on the status of cancer, 1975–2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst 2005; 97: 1407– 27. 10.1093/jnci/dji289 16204691 · DOI
  20. [25]Kanda M, Knight S, Topazian M, et al Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts. Gut 2013; 62: 1024– 33. 10.1136/gutjnl-2012-302823 22859495 PMC3893110 · DOI
  21. [26]Klein AP, Lindstrom S, Mendelsohn JB, et al An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. PLoS ONE 2013; 8: e72311 10.1371/journal.pone.0072311 24058443 PMC3772857 · DOI · Paper page
  22. [27]Klein AP Identifying people at a high risk of developing pancreatic cancer. Nat Rev Cancer 2013; 13: 66– 74. 10.1038/nrc3420 23222481 PMC3649844 · DOI
  23. [28]Chang KJ, Parasher G, Christie C, et al Risk of pancreatic adenocarcinoma: disparity between African Americans and other race/ethnic groups. Cancer 2005; 103: 349– 57. 10.1002/cncr.20771 15593353 · DOI
  24. [29]Wray CJ, Castro-Echeverry E, Silberfein EJ, et al A multi-institutional study of pancreatic cancer in Harris County, Texas: race predicts treatment and survival. Ann Surg Oncol 2012; 19: 2776– 81. 10.1245/s10434-012-2361-z 22526908 · DOI
  25. [30]Arnold LD, Patel AV, Yan Y, et al Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity? Cancer Epidemiol Biomarkers Prev 2009; 18: 2397– 405. 10.1158/1055-9965.EPI-09-0080 19723915 PMC3630792 · DOI
  26. [31]James TA, Sheldon DG, Rajput A, et al Risk factors associated with earlier age of onset in familial pancreatic carcinoma. Cancer 2004; 101: 2722– 6. 10.1002/cncr.20700 15534880 · DOI
  27. [32]Anderson MA, Zolotarevsky E, Cooper KL, et al Alcohol and tobacco lower the age of presentation in sporadic pancreatic cancer in a dose-dependent manner: a multicenter study. Am J Gastroenterol 2012; 107: 1730– 9. 10.1038/ajg.2012.288 22929760 PMC3923585 · DOI · Paper page
  28. [33]Sohn TA, Yeo CJ, Cameron JL, et al Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 2000; 4: 567– 79. 10.1016/S1091-255X(00)80105-5 11307091 · DOI
  29. [34]Axelson H, Fredlund E, Ovenberger M, et al Hypoxia-induced dedifferentiation of tumor cells—a mechanism behind heterogeneity and aggressiveness of solid tumors. Semin Cell Dev Biol 2005; 16: 554– 63. 10.1016/j.semcdb.2005.03.007 16144692 · DOI
  30. [35]Bull K, Spiegelhalter DJ Survival analysis in observational studies. Stat Med 1997; 16: 1041– 74. 10.1002/(SICI)1097-0258(19970515)16:9<1041::AID-SIM506>3.0.CO;2-F 9160498 · DOI
  31. [36]Cain KC, Harlow SD, Little RJ, et al Bias due to left truncation and left censoring in longitudinal studies of developmental and disease processes. Am J Epidemiol 2011; 173: 1078– 84. 10.1093/aje/kwq481 21422059 PMC3121224 · DOI
  32. [37]Park HS, Lloyd S, Decker RH, et al Limitations and biases of the Surveillance, Epidemiology, and End Results database. Curr Probl Cancer 2012; 36: 216– 24. 10.1016/j.currproblcancer.2012.03.011 22481009 · DOI

Cited by

Sorted by citations

Authors
Yu, J., Blackford, A. L., dal Molin, M., Wolfgang, C. L., & Goggins, M.
Affiliations
  • Johns Hopkins University (US)
  • Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Corresponding author
Goggins, Michael
ORCID
Venue
Gut
Publisher
BMJ
Published
2015-01-30
Volume
64
Issue
11
Pages
1783-1789
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gutjnl-2014-308653
PMC
PMC4520782
OpenAlex
W2133272421
Cited by
224
References
5
Citations by year
2026: 13 · 2025: 13 · 2024: 29 · 2023: 18 · 2022: 26 · 2021: 28 · 2020: 25 · 2019: 13 · 2018: 12 · 2017: 25 · 2016: 16 · 2015: 6
FWCI
8.59
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Gut (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • American Association for Cancer Research
  • Pancreatic Cancer Action Network
  • National Institutes of Health (CA62924)
  • National Cancer Institute (P50CA062924, R01CA176828, CA 62924)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
  • Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
Keywords
pancreatic ductal adenocarcinoma, tumor progression, TNM staging, age at diagnosis, tumor size, tumor stage, African American ethnicity, male gender, SEER database
MeSH terms
Adenocarcinoma, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Neoplasm Staging, Pancreatic Neoplasms, Time Factors, Disease Progression, Carcinoma, Pancreatic Ductal

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