Principal Investigator

Michael G.
Goggins
Awardee Organization

Johns Hopkins University
United States

Fiscal Year
2022
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Eligible
Project End Date

Using markers to improve pancreatic cancer screening and surveillance: a multi-center study

Patients diagnosed with Stage I pancreatic cancer have a much better outcome than most patients who present with advanced disease. The Cancer of the Pancreas Screening (CAPS) study currently follows a familial/genetic “high-risk” cohort of ~1500 patients undergo regular pancreatic surveillance. Recent results from the CAPS program indicate that most patients who maintain regular surveillance are down-staged, many are diagnosed with Stage I pancreatic cancer and achieve long-term survival. Circulating tumor marker tests are not currently used for pancreas surveillance, but we propose to evaluate blood tests for patients undergoing pancreatic surveillance. We will evaluate the use of tumor marker gene tests to better define an individual’s tumor marker normal reference range. We will evaluate the use of plasma MR spectroscopy as a diagnostic test that utilizes artificial-intelligence methods to detect subtle circulating metabolic changes associated with having pancreatic cancer. We will also determine if blood biomarker changes occur before the diagnosis of pancreatic cancer in our cohort. The addition of annual blood tests to pancreatic surveillance is expected to improve the detection of early-stage pancreatic cancer. We will continue to evaluate the long-term outcomes of patients in our cohort and bank biospecimens for future biomarker studies.

Publications

  • Suenaga M, Dudley B, Karloski E, Borges M, Irene Canto M, Brand RE, Goggins M. The Effect of Pancreatic Juice Collection Time on the Detection of KRAS Mutations. Pancreas. 2018 Jan;47(1):35-39. PMID: 29200129
  • Furniss CS, Yurgelun MB, Ukaegbu C, Constantinou PE, Lafferty CC, Talcove-Berko ER, Schwartz AN, Stopfer JE, Underhill-Blazey M, Kenner B, Nelson SH, Okumura S, Law S, Zhou AY, Coffin TB, Rodriguez NJ, Uno H, Ocean AJ, McAllister F, Lowy AM, Lippman SM, Klein AP, Madlensky L, Petersen GM, Garber JE, Goggins MG, Maitra A, Syngal S. Novel Models of Genetic Education and Testing for Pancreatic Cancer Interception: Preliminary Results from the GENERATE Study. Cancer prevention research (Philadelphia, Pa.). 2021 Nov;14(11):1021-1032. Epub 2021 Oct 8. PMID: 34625409
  • Canto MI, Kerdsirichairat T, Yeo CJ, Hruban RH, Shin EJ, Almario JA, Blackford A, Ford M, Klein AP, Javed AA, Lennon AM, Zaheer A, Kamel IR, Fishman EK, Burkhart R, He J, Makary M, Weiss MJ, Schulick RD, Goggins MG, Wolfgang CL. Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2020 May;24(5):1101-1110. Epub 2019 Jun 13. PMID: 31197699
  • Hata T, Suenaga M, Marchionni L, Macgregor-Das A, Yu J, Shindo K, Tamura K, Hruban RH, Goggins M. Genome-Wide Somatic Copy Number Alterations and Mutations in High-Grade Pancreatic Intraepithelial Neoplasia. The American journal of pathology. 2018 Jul;188(7):1723-1733. Epub 2018 Apr 22. PMID: 29684357
  • Katona BW, Brand RE, Canto MI, Chak A, Farrell JJ, Kastrinos F, Rustgi AK, Stoffel EM, Syngal S, Goggins M, CAPS5 Study Consortium. Screening for Pancreatic Ductal Adenocarcinoma: Are We Asking the Impossible?-Letter. Cancer prevention research (Philadelphia, Pa.). 2021 Oct;14(10):973-974. PMID: 34607877
  • Dbouk M, Katona BW, Brand RE, Chak A, Syngal S, Farrell JJ, Kastrinos F, Stoffel EM, Canto MI, Goggins M. Reply to S. Raoof. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Feb 10;41(5):1147-1149. Epub 2022 Oct 31. PMID: 36315911
  • Goggins M, Overbeek KA, Brand R, Syngal S, Del Chiaro M, Bartsch DK, Bassi C, Carrato A, Farrell J, Fishman EK, Fockens P, Gress TM, van Hooft JE, Hruban RH, Kastrinos F, Klein A, Lennon AM, Lucas A, Park W, Rustgi A, Simeone D, Stoffel E, Vasen HFA, Cahen DL, Canto MI, Bruno M, International Cancer of the Pancreas Screening (CAPS) consortium, Arcidiacono PG, Ashida R, Ausems M, Besselink M, Biermann K, Bonsing B, Brentnall T, Chak A, Early D, Castillo CF, Frucht H, Furukawa T, Gallinger S, Geurts J, Koerkamp BG, Hammel P, Hes F, Iglesias-Garcia J, Kamel I, Kitano M, Klöppel G, Krak N, Kurtz R, Kwon R, Lachter J, Lee J, Levy M, Malleo G, Meguid C, Maitra A, Margolis D, Offerhaus J, Olson S, Paiella S, Park W, Petersen G, Poley JW, Real FX, Saltzman J, Schulick R, Stoita A, Takaori K, Tanaka M, Tamm E, Topazian M, Vazquez-Sequeiros E, Vleggaar F, Vos Tot Nederveen Cappel W, Yeo C, Wasser M, Wagner A, Wallace M, Wolfgang C, Wood L. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020 Jan;69(1):7-17. Epub 2019 Oct 31. PMID: 31672839
  • Suenaga M, Sadakari Y, Almario JA, Borges M, Lennon AM, Shin EJ, Canto MI, Goggins M. Using an endoscopic distal cap to collect pancreatic fluid from the ampulla (with video). Gastrointestinal endoscopy. 2017 Dec;86(6):1152-1156.e2. Epub 2017 Mar 1. PMID: 28259593
  • Kawamoto M, Yoshida T, Tamura K, Dbouk M, Canto MI, Burkhart R, He J, Roberts NJ, Klein AP, Goggins M. Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2022 Nov;22(7):959-964. Epub 2022 Aug 17. PMID: 35995657
  • Akshintala VS, Talukdar R, Singh VK, Goggins M. The Gut Microbiome in Pancreatic Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019 Jan;17(2):290-295. Epub 2018 Aug 23. PMID: 30144522
  • Ayars M, Eshleman J, Goggins M. Susceptibility of ATM-deficient pancreatic cancer cells to radiation. Cell cycle (Georgetown, Tex.). 2017 May 19;16(10):991-998. Epub 2017 Apr 28. PMID: 28453388
  • Douville C, Cohen JD, Ptak J, Popoli M, Schaefer J, Silliman N, Dobbyn L, Schoen RE, Tie J, Gibbs P, Goggins M, Wolfgang CL, Wang TL, Shih IM, Karchin R, Lennon AM, Hruban RH, Tomasetti C, Bettegowda C, Kinzler KW, Papadopoulos N, Vogelstein B. Assessing aneuploidy with repetitive element sequencing. Proceedings of the National Academy of Sciences of the United States of America. 2020 Mar 3;117(9):4858-4863. Epub 2020 Feb 19. PMID: 32075918
  • Katona BW, Long JM, Ahmad NA, Attalla S, Bradbury AR, Carpenter EL, Clark DF, Constantino G, Das KK, Domchek SM, Dudzik C, Ebrahimzadeh J, Ginsberg GG, Heiman J, Kochman ML, Maxwell KN, McKenna DB, Powers J, Shah PD, Wangensteen KJ, Rustgi AK. EUS-based Pancreatic Cancer Surveillance in BRCA1/BRCA2/PALB2/ATM Carriers Without a Family History of Pancreatic Cancer. Cancer prevention research (Philadelphia, Pa.). 2021 Nov;14(11):1033-1040. Epub 2021 Aug 2. PMID: 34341011
  • Hata T, Dal Molin M, Suenaga M, Yu J, Pittman M, Weiss M, Canto MI, Wolfgang C, Lennon AM, Hruban RH, Goggins M. Cyst Fluid Telomerase Activity Predicts the Histologic Grade of Cystic Neoplasms of the Pancreas. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Oct 15;22(20):5141-5151. Epub 2016 May 26. PMID: 27230749
  • Tamura K, Yu J, Hata T, Suenaga M, Shindo K, Abe T, MacGregor-Das A, Borges M, Wolfgang CL, Weiss MJ, He J, Canto MI, Petersen GM, Gallinger S, Syngal S, Brand RE, Rustgi A, Olson SH, Stoffel E, Cote ML, Zogopoulos G, Potash JB, Goes FS, McCombie RW, Zandi PP, Pirooznia M, Kramer M, Parla J, Eshleman JR, Roberts NJ, Hruban RH, Klein AP, Goggins M. Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America. 2018 May 1;115(18):4767-4772. Epub 2018 Apr 18. PMID: 29669919
  • Underhill-Blazey M, Blonquist T, Lawrence J, Hong F, Yurgelun MB, Syngal S. Health behaviours and beliefs in individuals with familial pancreatic cancer. Familial cancer. 2019 Oct;18(4):457-464. PMID: 31522335
  • Springer S, Masica DL, Dal Molin M, Douville C, Thoburn CJ, Afsari B, Li L, Cohen JD, Thompson E, Allen PJ, Klimstra DS, Schattner MA, Schmidt CM, Yip-Schneider M, Simpson RE, Fernandez-Del Castillo C, Mino-Kenudson M, Brugge W, Brand RE, Singhi AD, Scarpa A, Lawlor R, Salvia R, Zamboni G, Hong SM, Hwang DW, Jang JY, Kwon W, Swan N, Geoghegan J, Falconi M, Crippa S, Doglioni C, Paulino J, Schulick RD, Edil BH, Park W, Yachida S, Hijioka S, van Hooft J, He J, Weiss MJ, Burkhart R, Makary M, Canto MI, Goggins MG, Ptak J, Dobbyn L, Schaefer J, Sillman N, Popoli M, Klein AP, Tomasetti C, Karchin R, Papadopoulos N, Kinzler KW, Vogelstein B, Wolfgang CL, Hruban RH, Lennon AM. A multimodality test to guide the management of patients with a pancreatic cyst. Science translational medicine. 2019 Jul 17;11. (501). PMID: 31316009
  • Kumar S, Saumoy M, Oh A, Schneider Y, Brand RE, Chak A, Ginsberg GG, Kochman ML, Canto MI, Goggins MG, Hur C, Kastrinos F, Katona BW, Rustgi AK. Threshold Analysis of the Cost-effectiveness of Endoscopic Ultrasound in Patients at High Risk for Pancreatic Ductal Adenocarcinoma. Pancreas. 2021 Jul 1;50(6):807-814. PMID: 34149034
  • He HJ, Stein EV, Konigshofer Y, Forbes T, Tomson FL, Garlick R, Yamada E, Godfrey T, Abe T, Tamura K, Borges M, Goggins M, Elmore S, Gulley ML, Larson JL, Ringel L, Haynes BC, Karlovich C, Williams PM, Garnett A, Ståhlberg A, Filges S, Sorbara L, Young MR, Srivastava S, Cole KD. Multilaboratory Assessment of a New Reference Material for Quality Assurance of Cell-Free Tumor DNA Measurements. The Journal of molecular diagnostics : JMD. 2019 Jul;21(4):658-676. Epub 2019 May 2. PMID: 31055023
  • Shindo K, Yu J, Suenaga M, Fesharakizadeh S, Cho C, Macgregor-Das A, Siddiqui A, Witmer PD, Tamura K, Song TJ, Navarro Almario JA, Brant A, Borges M, Ford M, Barkley T, He J, Weiss MJ, Wolfgang CL, Roberts NJ, Hruban RH, Klein AP, Goggins M. Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017 Oct 20;35(30):3382-3390. Epub 2017 Aug 2. PMID: 28767289
  • Poruk KE, Griffin J, Makary MA, He J, Cameron JL, Weiss MJ, Wood LD, Goggins M, Wolfgang CL. Blood Type as a Predictor of High-Grade Dysplasia and Associated Malignancy in Patients with Intraductal Papillary Mucinous Neoplasms. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2019 Mar;23(3):477-483. Epub 2018 Sep 4. PMID: 30187322
  • Hata T, Dal Molin M, Hong SM, Tamura K, Suenaga M, Yu J, Sedogawa H, Weiss MJ, Wolfgang CL, Lennon AM, Hruban RH, Goggins MG. Predicting the Grade of Dysplasia of Pancreatic Cystic Neoplasms Using Cyst Fluid DNA Methylation Markers. Clinical cancer research : an official journal of the American Association for Cancer Research. 2017 Jul 15;23(14):3935-3944. Epub 2017 Feb 1. PMID: 28148542
  • Canto MI, Almario JA, Schulick RD, Yeo CJ, Klein A, Blackford A, Shin EJ, Sanyal A, Yenokyan G, Lennon AM, Kamel IR, Fishman EK, Wolfgang C, Weiss M, Hruban RH, Goggins M. Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance. Gastroenterology. 2018 Sep;155(3):740-751.e2. Epub 2018 May 24. PMID: 29803839
  • Underhill M, Hong F, Lawrence J, Blonquist T, Syngal S. Relationship between individual and family characteristics and psychosocial factors in persons with familial pancreatic cancer. Psycho-oncology. 2018 Jul;27(7):1711-1718. Epub 2018 Apr 19. PMID: 29570238
  • Ayars M, O'Sullivan E, Macgregor-Das A, Shindo K, Kim H, Borges M, Yu J, Hruban RH, Goggins M. IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth. Oncotarget. 2017 Aug 3;8(48):83370-83383. doi: 10.18632/oncotarget.19848. eCollection 2017 Oct 13. PMID: 29137350
  • Abe T, Koi C, Kohi S, Song KB, Tamura K, Macgregor-Das A, Kitaoka N, Chuidian M, Ford M, Dbouk M, Borges M, He J, Burkhart R, Wolfgang CL, Klein AP, Eshleman JR, Hruban RH, Canto MI, Goggins M. Gene Variants That Affect Levels of Circulating Tumor Markers Increase Identification of Patients With Pancreatic Cancer. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2020 May;18(5):1161-1169.e5. Epub 2019 Oct 30. PMID: 31676359
  • Kohi S, Macgregor-Das A, Dbouk M, Yoshida T, Chuidian M, Abe T, Borges M, Lennon AM, Shin EJ, Canto MI, Goggins M. Alterations in the Duodenal Fluid Microbiome of Patients With Pancreatic Cancer. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Feb;20(2):e196-e227. Epub 2020 Nov 5. PMID: 33161160
  • Lennon AM, Canto MI. Pancreatic Cysts - Part 2: Should We Be Less Cyst Centric? Pancreas. 2017 Jul;46(6):745-750. PMID: 28609361
  • Kawamoto M, Kohi S, Abe T, Dbouk M, Macgregor-Das A, Koi C, Song KB, Borges M, Sugimine R, Laheru D, Hruban RH, Roberts N, Klein AP, Goggins M. Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis. International journal of cancer. 2022 Apr 1;150(7):1123-1133. Epub 2021 Dec 6. PMID: 34817877
  • Yu J, Sadakari Y, Shindo K, Suenaga M, Brant A, Almario JAN, Borges M, Barkley T, Fesharakizadeh S, Ford M, Hruban RH, Shin EJ, Lennon AM, Canto MI, Goggins M. Digital next-generation sequencing identifies low-abundance mutations in pancreatic juice samples collected from the duodenum of patients with pancreatic cancer and intraductal papillary mucinous neoplasms. Gut. 2017 Sep;66(9):1677-1687. Epub 2016 Jul 18. PMID: 27432539
  • Biller LH, Wolpin BM, Goggins M. Inherited Pancreatic Cancer Syndromes and High-Risk Screening. Surgical oncology clinics of North America. 2021 Oct;30(4):773-786. Epub 2021 Jul 22. PMID: 34511196
  • Blackford AL, Canto MI, Klein AP, Hruban RH, Goggins M. Recent Trends in the Incidence and Survival of Stage 1A Pancreatic Cancer: A Surveillance, Epidemiology, and End Results Analysis. Journal of the National Cancer Institute. 2020 Nov 1;112(11):1162-1169. PMID: 31958122
  • Hata T, Dal Molin M, McGregor-Das A, Song TJ, Wolfgang C, Eshleman JR, Hruban RH, Goggins M. Simple Detection of Telomere Fusions in Pancreatic Cancer, Intraductal Papillary Mucinous Neoplasm, and Pancreatic Cyst Fluid. The Journal of molecular diagnostics : JMD. 2018 Jan;20(1):46-55. Epub 2017 Dec 8. PMID: 29229290
  • Macgregor-Das A, Yu J, Tamura K, Abe T, Suenaga M, Shindo K, Borges M, Koi C, Kohi S, Sadakari Y, Dal Molin M, Almario JA, Ford M, Chuidian M, Burkhart R, He J, Hruban RH, Eshleman JR, Klein AP, Wolfgang CL, Canto MI, Goggins M. Detection of Circulating Tumor DNA in Patients with Pancreatic Cancer Using Digital Next-Generation Sequencing. The Journal of molecular diagnostics : JMD. 2020 Jun;22(6):748-756. Epub 2020 Mar 20. PMID: 32205290
  • Winnard PT Jr, Bharti SK, Sharma RK, Krishnamachary B, Mironchik Y, Penet MF, Goggins MG, Maitra A, Kamel I, Horton KM, Jacobs MA, Bhujwalla ZM. Brain metabolites in cholinergic and glutamatergic pathways are altered by pancreatic cancer cachexia. Journal of cachexia, sarcopenia and muscle. 2020 Dec;11(6):1487-1500. Epub 2020 Oct 2. PMID: 33006443
  • Tie J, Wang Y, Cohen J, Li L, Hong W, Christie M, Wong HL, Kosmider S, Wong R, Thomson B, Choi J, Fox A, Field K, Burge M, Shannon J, Kotasek D, Tebbutt NC, Karapetis C, Underhill C, Haydon A, Schaeffer J, Ptak J, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study. PLoS medicine. 2021 May 3;18(5):e1003620. doi: 10.1371/journal.pmed.1003620. eCollection 2021 May. PMID: 33939694
  • Tanaka H, Tamura K, Abe T, Yoshida T, Macgregor-Das A, Dbouk M, Blackford AL, Borges M, Lennon AM, He J, Burkhart R, Canto MI, Goggins M. Serum Carboxypeptidase Activity and Genotype-Stratified CA19-9 to Detect Early-Stage Pancreatic Cancer. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Oct;20(10):2267-2275.e2. Epub 2021 Oct 12. PMID: 34648951
  • Tie J, Cohen JD, Lo SN, Wang Y, Li L, Christie M, Lee M, Wong R, Kosmider S, Skinner I, Wong HL, Lee B, Burge ME, Yip D, Karapetis CS, Price TJ, Tebbutt NC, Haydon AM, Ptak J, Schaeffer MJ, Silliman N, Dobbyn L, Popoli M, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Prognostic significance of postsurgery circulating tumor DNA in nonmetastatic colorectal cancer: Individual patient pooled analysis of three cohort studies. International journal of cancer. 2021 Feb 15;148(4):1014-1026. Epub 2020 Oct 6. PMID: 32984952
  • Dbouk M, Katona BW, Brand RE, Chak A, Syngal S, Farrell JJ, Kastrinos F, Stoffel EM, Blackford AL, Rustgi AK, Dudley B, Lee LS, Chhoda A, Kwon R, Ginsberg GG, Klein AP, Kamel I, Hruban RH, He J, Shin EJ, Lennon AM, Canto MI, Goggins M. The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022 Oct 1;40(28):3257-3266. Epub 2022 Jun 15. PMID: 35704792
  • Saba H, Goggins M. Familial Pancreatic Cancer. Gastroenterology clinics of North America. 2022 Sep;51(3):561-575. Epub 2022 Aug 29. PMID: 36153110
  • Stoffel EM, Brand RE, Goggins M. Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention. Gastroenterology. 2023 Apr;164(5):752-765. Epub 2023 Feb 18. PMID: 36804602