Marcia Irene Canto1, Jose Alejandro Almario2, Richard D Schulick3, Charles J Yeo4, Alison Klein5, Amanda Blackford5, Eun Ji Shin6, Abanti Sanyal7, Gayane Yenokyan7, Anne Marie Lennon6, Ihab R Kamel8, Elliot K Fishman8, Christopher Wolfgang9, Matthew Weiss9, Ralph H Hruban10, Michael Goggins2. 1. Department of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address: mcanto@jhmi.edu. 2. Department of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. 3. Department of Surgery, University of Colorado School of Medicine, Denver, Colorado. 4. Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania. 5. Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. 6. Department of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. 7. The Johns Hopkins Biostatistics Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 8. Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. 9. Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. 10. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Abstract
BACKGROUND & AIMS: Screening of individuals who have a high risk of pancreatic ductal adenocarcinoma (PDAC), because of genetic factors, frequently leads to identification of pancreatic lesions. We investigated the incidence of PDAC and risk factors for neoplastic progression in individuals at high risk for PDAC enrolled in a long-term screening study. METHODS: We analyzed data from 354 individuals at high risk for PDAC (based on genetic factors of family history), enrolled in Cancer of the Pancreas Screening cohort studies at tertiary care academic centers from 1998 through 2014 (median follow-up time, 5.6 years). All subjects were evaluated at study entry (baseline) by endoscopic ultrasonography and underwent surveillance with endoscopic ultrasonography, magnetic resonance imaging, and/or computed tomography. The primary endpoint was the cumulative incidence of PDAC, pancreatic intraepithelial neoplasia grade 3, or intraductal papillary mucinous neoplasm with high-grade dysplasia (HGD) after baseline. We performed multivariate Cox regression and Kaplan-Meier analyses. RESULTS: During the follow-up period, pancreatic lesions with worrisome features (solid mass, multiple cysts, cyst size > 3 cm, thickened/enhancing walls, mural nodule, dilated main pancreatic duct > 5 mm, or abrupt change in duct caliber) or rapid cyst growth (>4 mm/year) were detected in 68 patients (19%). Overall, 24 of 354 patients (7%) had neoplastic progression (14 PDACs and 10 HGDs) over a 16-year period; the rate of progression was 1.6%/year, and 93% had detectable lesions with worrisome features before diagnosis of the PDAC or HGD. Nine of the 10 PDACs detected during routine surveillance were resectable; a significantly higher proportion of patients with resectable PDACs survived 3 years (85%) compared with the 4 subjects with symptomatic, unresectable PDACs (25%), which developed outside surveillance (log rank P < .0001). Neoplastic progression occurred at a median age of 67 years; the median time from baseline screening until PDAC diagnosis was 4.8 years (interquartile range, 1.6-6.9 years). CONCLUSIONS: In a long-term (16-year) follow-up study of individuals at high-risk for PDAC, we found most PDACs detected during surveillance (9/10) to be resectable, and 85% of these patients survived for 3 years. We identified radiologic features associated with neoplastic progression.
BACKGROUND & AIMS: Screening of individuals who have a high risk of pancreatic ductal adenocarcinoma (PDAC), because of genetic factors, frequently leads to identification of pancreatic lesions. We investigated the incidence of PDAC and risk factors for neoplastic progression in individuals at high risk for PDAC enrolled in a long-term screening study. METHODS: We analyzed data from 354 individuals at high risk for PDAC (based on genetic factors of family history), enrolled in Cancer of the Pancreas Screening cohort studies at tertiary care academic centers from 1998 through 2014 (median follow-up time, 5.6 years). All subjects were evaluated at study entry (baseline) by endoscopic ultrasonography and underwent surveillance with endoscopic ultrasonography, magnetic resonance imaging, and/or computed tomography. The primary endpoint was the cumulative incidence of PDAC, pancreatic intraepithelial neoplasia grade 3, or intraductal papillary mucinous neoplasm with high-grade dysplasia (HGD) after baseline. We performed multivariate Cox regression and Kaplan-Meier analyses. RESULTS: During the follow-up period, pancreatic lesions with worrisome features (solid mass, multiple cysts, cyst size > 3 cm, thickened/enhancing walls, mural nodule, dilated main pancreatic duct > 5 mm, or abrupt change in duct caliber) or rapid cyst growth (>4 mm/year) were detected in 68 patients (19%). Overall, 24 of 354 patients (7%) had neoplastic progression (14 PDACs and 10 HGDs) over a 16-year period; the rate of progression was 1.6%/year, and 93% had detectable lesions with worrisome features before diagnosis of the PDAC or HGD. Nine of the 10 PDACs detected during routine surveillance were resectable; a significantly higher proportion of patients with resectable PDACs survived 3 years (85%) compared with the 4 subjects with symptomatic, unresectable PDACs (25%), which developed outside surveillance (log rank P < .0001). Neoplastic progression occurred at a median age of 67 years; the median time from baseline screening until PDAC diagnosis was 4.8 years (interquartile range, 1.6-6.9 years). CONCLUSIONS: In a long-term (16-year) follow-up study of individuals at high-risk for PDAC, we found most PDACs detected during surveillance (9/10) to be resectable, and 85% of these patients survived for 3 years. We identified radiologic features associated with neoplastic progression.
Authors: Marc F Catalano; Anand Sahai; Michael Levy; Joseph Romagnuolo; Maurits Wiersema; William Brugge; Martin Freeman; Kenji Yamao; Marcia Canto; Lyndon V Hernandez Journal: Gastrointest Endosc Date: 2009-02-24 Impact factor: 9.427
Authors: Wilson T Kwong; Robert D Lawson; Gordon Hunt; Syed M Fehmi; James A Proudfoot; Ronghui Xu; Andrew Giap; Raymond S Tang; Ingrid Gonzalez; Mary L Krinsky; Thomas J Savides Journal: Dig Dis Sci Date: 2015-04-30 Impact factor: 3.199
Authors: Mee Joo Kang; Jin-Young Jang; Soo Jin Kim; Kyoung Bun Lee; Ji Kon Ryu; Yong-Tae Kim; Yong Bum Yoon; Sun-Whe Kim Journal: Clin Gastroenterol Hepatol Date: 2010-09-17 Impact factor: 11.382
Authors: J W Poley; I Kluijt; D J Gouma; F Harinck; A Wagner; C Aalfs; C H J van Eijck; A Cats; E J Kuipers; Y Nio; P Fockens; M J Bruno Journal: Am J Gastroenterol Date: 2009-06-02 Impact factor: 10.864
Authors: Fay Kastrinos; Bhramar Mukherjee; Nabihah Tayob; Fei Wang; Jennifer Sparr; Victoria M Raymond; Prathap Bandipalliam; Elena M Stoffel; Stephen B Gruber; Sapna Syngal Journal: JAMA Date: 2009-10-28 Impact factor: 56.272
Authors: P Langer; P H Kann; V Fendrich; N Habbe; M Schneider; M Sina; E P Slater; J T Heverhagen; T M Gress; M Rothmund; D K Bartsch Journal: Gut Date: 2009-05-25 Impact factor: 23.059
Authors: Hans Vasen; Isaura Ibrahim; Carmen Guillen Ponce; Emily P Slater; Elvira Matthäi; Alfredo Carrato; Julie Earl; Kristin Robbers; Anneke M van Mil; Thomas Potjer; Bert A Bonsing; Wouter H de Vos Tot Nederveen Cappel; Wilma Bergman; Martin Wasser; Hans Morreau; Günter Klöppel; Christoph Schicker; Martin Steinkamp; Jens Figiel; Irene Esposito; Evelina Mocci; Enrique Vazquez-Sequeiros; Alfonso Sanjuanbenito; Maria Muñoz-Beltran; José Montans; Peter Langer; Volker Fendrich; Detlef K Bartsch Journal: J Clin Oncol Date: 2016-04-25 Impact factor: 44.544
Authors: D K Bartsch; K Dietzel; M Bargello; E Matthaei; G Kloeppel; I Esposito; J T Heverhagen; T M Gress; E P Slater; P Langer Journal: Fam Cancer Date: 2013-03 Impact factor: 2.375
Authors: Toshiya Abe; Amanda L Blackford; Koji Tamura; Madeline Ford; Patrick McCormick; Miguel Chuidian; Jose Alejandro Almario; Michael Borges; Anne Marie Lennon; Eun Ji Shin; Alison P Klein; Ralph H Hruban; Marcia I Canto; Michael Goggins Journal: J Clin Oncol Date: 2019-03-18 Impact factor: 44.544
Authors: Stephen P Pereira; Lucy Oldfield; Alexander Ney; Phil A Hart; Margaret G Keane; Stephen J Pandol; Debiao Li; William Greenhalf; Christie Y Jeon; Eugene J Koay; Christopher V Almario; Christopher Halloran; Anne Marie Lennon; Eithne Costello Journal: Lancet Gastroenterol Hepatol Date: 2020-03-02
Authors: Michael Skaro; Neha Nanda; Christian Gauthier; Matthäus Felsenstein; Zhengdong Jiang; Miaozhen Qiu; Koji Shindo; Jun Yu; Danielle Hutchings; Ammar A Javed; Ross Beckman; Jin He; Christopher L Wolfgang; Elizabeth Thompson; Ralph H Hruban; Alison P Klein; Michael Goggins; Laura D Wood; Nicholas J Roberts Journal: Gastroenterology Date: 2019-02-01 Impact factor: 22.682
Authors: Marcia Irene Canto; Tossapol Kerdsirichairat; Charles J Yeo; Ralph H Hruban; Eun Ji Shin; Jose Alejandro Almario; Amanda Blackford; Madeline Ford; Alison P Klein; Ammar A Javed; Anne Marie Lennon; Atif Zaheer; Ihab R Kamel; Elliot K Fishman; Richard Burkhart; Jin He; Martin Makary; Matthew J Weiss; Richard D Schulick; Michael G Goggins; Christopher L Wolfgang Journal: J Gastrointest Surg Date: 2019-06-13 Impact factor: 3.452
Authors: Shounak Majumder; Massimo Raimondo; William R Taylor; Tracy C Yab; Calise K Berger; Brian A Dukek; Xiaoming Cao; Patrick H Foote; Chung Wah Wu; Mary E Devens; Douglas W Mahoney; Thomas C Smyrk; Rahul Pannala; Suresh T Chari; Santhi Swaroop Vege; Mark D Topazian; Bret T Petersen; Michael J Levy; Elizabeth Rajan; Ferga C Gleeson; Barham Abu Dayyeh; Cuong C Nguyen; Douglas O Faigel; Timothy A Woodward; Michael B Wallace; Gloria Petersen; Hatim T Allawi; Graham P Lidgard; John B Kisiel; David A Ahlquist Journal: Clin Gastroenterol Hepatol Date: 2019-07-16 Impact factor: 11.382