Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium

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Abstract

Background and aim

The International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals).

Methods

A modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed.

Results

Consensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline ATM mutation carriers with one affected first-degree relative are now considered eligible for surveillance. Experts agreed that preferred surveillance tests are endoscopic ultrasound and MRI/magnetic retrograde cholangiopancreatography, but no consensus was reached on how to alternate these modalities. Annual surveillance is recommended in the absence of concerning lesions. Main areas of disagreement included if and how surveillance should be performed for hereditary pancreatitis, and the management of indeterminate lesions.

Conclusions

Pancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.

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Most cited references 89

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ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors

M. Falconi, B Eriksson, G. Kaltsas … (2016)

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European evidence-based guidelines on pancreatic cystic neoplasms

(2018)

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring 5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

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Elevated circulating branched chain amino acids are an early event in pancreatic adenocarcinoma development

Jared Mayers, Chen-Chen Wu, Clary Clish … (2014)

Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months 1 . PDAC has been linked with obesity and glucose intolerance 2-4 , but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from pancreatic cancer cases and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched chain amino acids (BCAAs) are associated with a greater than 2–fold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years prior to diagnosis when occult disease is likely present. We show that plasma BCAAs are also elevated in mice with early stage pancreatic cancers driven by mutant Kras expression, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early stage disease. Together, these findings suggest that increased whole–body protein breakdown is an early event in development of PDAC.

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Journal

Journal ID (nlm-journal-id): 2985108R

Journal ID (pubmed-jr-id): 3923

Journal ID (nlm-ta): Gut

Journal ID (iso-abbrev): Gut

Title: Gut

ISSN (Print): 0017-5749

ISSN (Electronic): 1468-3288

Publication date Nihms-submitted: 29 April 2020

Publication date (Electronic): 31 October 2019

Publication date (Print): January 2020

Publication date PMC-release: 15 June 2020

Volume: 69

Issue: 1

Pages: 7-17

Affiliations

[1 ]Pathology, Medicine Oncology, Johns Hopkins University, Baltimore, Maryland, USA

[2 ]Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands

[3 ]Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

[4 ]GI Cancer Genetics and Prevention Program, Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA

[5 ]Department of Surgery, Division of Surgical Oncology, Denver, Colorado, USA

[6 ]Division of Visceral, Thoracic and Vascular Surgery, University of Marburg, Marburg, Germany

[7 ]Department of Surgey, University of Verona, Verona, Italy

[8 ]Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain

[9 ]Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

[10 ]The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, Maryland, USA

[11 ]Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands

[12 ]Gastroenterology, Endocrinology, Metabolism and Infectiology, University of Marburg, Marburg, Germany

[13 ]Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands

[14 ]Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA

[15 ]Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City, New York, USA

[16 ]Division of Digestive and Liver Diseases, Columbia University, New York City, New York, USA

[17 ]Oncology, Johns Hopkins University, Baltimore, Maryland, USA

[18 ]Medicine, Johns Hopkins University, Baltimore, Maryland, USA

[19 ]Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA

[20 ]New York University Medical Center, New York City, New York, USA

[21 ]University of Michigan, Ann Arbor, Michigan, USA

[22 ]Gastroenterology and Hepatology, Leiden University, Leiden, The Netherlands

Author notes

Collaborators International Cancer of the Pancreas Screening (CAPS) consortium Paolo Giorgio Arcidiacono, Reiko Ashida, Margreet Ausems, Marc Besselink, Katharina Biermann, Bert Bonsing, Teri Brentnall, Amitabh Chak, Dayna Early, Carloz Fernandez-Del Castillo, Harold Frucht, Toru Furukawa, Steven Gallinger, Jennifer Geurts, Bas Groot Koerkamp, Pascal Hammel, Frederik Hes, Julio Iglesias-Garcia, Ihab Kamel, Masayuki Kitano, Günter Klöppel, Nanda Krak, Robert Kurtz, Richard Kwon, Jesse Lachter, Jeffrey Lee, Michael Levy, Giuseppe Malleo, Cheryl Meguid, Anirban Maitra, Daniel Margolis, Johan Offerhaus, Sara Olson, Salvatore Paiella, Walter Park, Gloria Petersen, Jan-Werner Poley, Francisco X Real, John Saltzman, Richard Schulick, Alina Stoita, Kyoichi Takaori, Masao Tanaka, Eric Tamm, Mark Topazian, Enrique Vazquez-Sequeiros, Frank Vleggaar, Wouter De Vos tot Nederveen Cappel, Charles Yeo, Martin Wasser, Anja Wagner, Michael Wallace, Christopher Wolfgang, Laura Wood.

Contributors The consensus meeting was initiated and organised by MG, MIC, MB, and DLC. The consensus study design was developed by KAO and revised and approved by MB, DLC, MG, and MIC. Relevant literature was collected and summarised by KAO. Presentations during the development workgroup meeting were given by MG, RB, MDC, EF, TMG, SS, MIC, and MB, and the discussions facilitated by JF and JEvH. All authors except KAO, and all previously mentioned study collaborators provided the data (votes) for this study. Data were collected and analysed by KAO. The results were critically reviewed by MB, DLC, MG, and MIC. The manuscript was drafted by MG, KAO, DLC, MIC, and MB. All authors approved the fnal manuscript.

Correspondence to Dr Michael Goggins, Pathology, Medicine Oncology, Johns Hopkins University, Baltimore, Maryland, USA; mgoggins@ 123456jhmi.edu

Author information

Michael Goggins http://orcid.org/0000-0002-4286-2296

Kasper Alexander Overbeek http://orcid.org/0000-0003-1829-9963

Thomas M Gress http://orcid.org/0000-0002-9333-5461

Walter Park http://orcid.org/0000-0001-8187-4188

Article

Accession ID: PMC7295005 Pmcid ID: PMC7295005 Pmc-uid ID: 7295005 Manuscript ID: nihpa1559700

DOI: 10.1136/gutjnl-2019-319352

PMC ID: 7295005

PubMed ID: 31672839

SO-VID: c30d548a-d2eb-4684-be21-3235fc7f0fc4

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Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium

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Abstract

Background and aim

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Cancer Metabolism

Most cited references 89

ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors

European evidence-based guidelines on pancreatic cystic neoplasms

Elevated circulating branched chain amino acids are an early event in pancreatic adenocarcinoma development

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