scholarly journals Long-term yield of pancreatic cancer surveillance in high-risk individuals

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323611
Author(s):  
Kasper A Overbeek ◽  
Iris J M Levink ◽  
Brechtje D M Koopmann ◽  
Femme Harinck ◽  
Ingrid C A W Konings ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Diagnostic Yield ◽  
Susceptibility Gene ◽  
Cancer Surveillance ◽  
Ductal Adenocarcinoma ◽  
Familial Pancreatic Cancer ◽  
Low Grade ◽  
Mutation Carriers

ObjectiveWe aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.DesignFrom 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.Results366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1–32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001).ConclusionThe diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

scholarly journals PancPRO: Risk Assessment for Individuals With a Family History of Pancreatic Cancer

2007 ◽  
Vol 25 (11) ◽  
pp. 1417-1422 ◽  
Author(s):  
Wenyi Wang ◽  
Sining Chen ◽  
Kieran A. Brune ◽  
Ralph H. Hruban ◽  
Giovanni Parmigiani ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pancreatic Cancer ◽  
Family History ◽  
High Risk ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Familial Pancreatic Cancer ◽  
Cancer Susceptibility Gene

Purpose The rapid fatality of pancreatic cancer is, in large part, the result of an advanced stage of diagnosis for the majority of patients. Identification of individuals at high risk of developing pancreatic cancer is a first step towards the early detection of this disease. Individuals who may harbor a major pancreatic cancer susceptibility gene are one such high-risk group. The goal of this study was to develop and validate PancPRO, a Mendelian model for pancreatic cancer risk prediction in individuals with familial pancreatic cancer, to identify high-risk individuals. Methods PancPRO was built by extending the Bayesian modeling framework developed for BRCAPRO, trained using published data, and validated using independent prospective data on 961 families enrolled onto the National Familial Pancreas Tumor Registry, including 26 individuals who developed incident pancreatic cancer during follow-up. Results We developed a risk prediction model, PancPRO, and free software for the estimation of pancreatic cancer susceptibility gene carrier probabilities and absolute pancreatic cancer risk. Model validation demonstrated an observed to predicted pancreatic cancer ratio of 0.83 (95% CI, 0.52 to 1.20) and high discriminatory ability, with an area under the receiver operating characteristic curve of 0.75 (95% CI, 0.68 to 0.81) for PancPRO. Conclusion PancPRO is the first risk prediction model for pancreatic cancer. When we validated our model using the largest registry of familial pancreatic cancer, our model provided accurate risk assessment. Our findings highlight the importance of detailed family history for clinical cancer risk assessment and demonstrate that accurate genetic risk assessment is possible even when the causative genes are not known.

scholarly journals Health behaviours and beliefs in individuals with familial pancreatic cancer

2019 ◽  
Vol 18 (4) ◽  
pp. 457-464 ◽  
Author(s):  
Meghan Underhill-Blazey ◽  
Traci Blonquist ◽  
Janette Lawrence ◽  
Fangxin Hong ◽  
Matthew B. Yurgelun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Alcohol Consumption ◽  
Cancer Surveillance ◽  
Comprehensive Cancer Center ◽  
Familial Pancreatic Cancer ◽  
Impact Of Event Scale ◽  
Event Scale ◽  
Modifiable Factors ◽  
Integrative Therapies

Abstract Individuals at high risk for pancreatic cancer are recommended surveillance and healthy lifestyle behaviours and patient experience with recommendations are understudied. To describe engagement and experience with surveillance, tobacco and alcohol use, health beliefs and motivation (Champion Health Belief Measure) and the relationship with personal, psychosocial (Impact of Event Scale), and familial characteristics. Interest in integrative therapies (complementary therapies) are described. A multi-site cross-sectional survey including individuals at high risk for pancreatic cancer with no diagnosis of pancreatic cancer who have been evaluated at a comprehensive cancer center. Descriptive statistics and Wilcoxon rank sum test and Fisher’s exact test were used to assess univariate associations. Of the 132 respondents (72% response rate), 92 (70%) reported undergoing surveillance which was associated with older age (p = 0.001). Of which, 36% and 51% report that magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS), respectively, were uncomfortable; 22% and 30% dread the next MRI or EUS, respectively. Of those who reported alcohol consumption (n = 88); 15% consumed 1 or more drinks daily and no alcohol consumption was associated with higher Impact of Event scale scores (p = 0.024). A total of six participants were currently smoking every day or some days. Participants reported high motivation to engage in heathy behaviours and 92% were interested in integrative therapies. In these select participants, most were engaging in pancreatic cancer surveillance, alcohol intake was moderate, and tobacco intake was minimal. Modifiable factors, such as experience and comfort with surveillance could be addressed. The sample is motivated to engage in behavioural health intervention.

scholarly journals Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1612
Author(s):  
Julie Earl ◽  
Emma Barreto ◽  
María E. Castillo ◽  
Raquel Fuentes ◽  
Mercedes Rodríguez-Garrote ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Somatic Mutation ◽  
Disease Status ◽  
Clinical Analysis ◽  
Cytotoxic Agents ◽  
Disease Stage ◽  
Ductal Adenocarcinoma ◽  
Familial Pancreatic Cancer ◽  
Circulating Free Dna

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

scholarly journals Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1090
Author(s):  
Hassan Sadozai ◽  
Animesh Acharjee ◽  
Thomas Gruber ◽  
Beat Gloor ◽  
Eva Karamitopoulou
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Disease Progression ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Ductal Adenocarcinoma ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition

Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.

scholarly journals Sa1365 – Patient-Reported Burden of Intensified Surveillance and Surgery in High-Risk Individuals Under Pancreatic Cancer Surveillance

2019 ◽  
Vol 156 (6) ◽  
pp. S-328
Author(s):  
Kasper A. Overbeek ◽  
Djuna Cahen ◽  
Anne Kamps ◽  
Ingrid C. Konings ◽  
Femme Harinck ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Cancer Surveillance ◽  
Patient Reported

scholarly journals Outcome of Pancreatic Cancer Surveillance Among High-Risk Individuals Tested for Germline Mutations in BRCA1 and BRCA2

2019 ◽  
Vol 12 (9) ◽  
pp. 599-608 ◽  
Author(s):  
Amethyst Saldia ◽  
Sara H. Olson ◽  
Pamela Nunes ◽  
Xiaolin Liang ◽  
Marguerite L. Samson ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Germline Mutations ◽  
Cancer Surveillance ◽  
Brca1 And Brca2

The Spanish familial pancreatic cancer registry panfam: Screening of high-risk individuals

Pancreatology ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. S126
Author(s):  
Carmen Guillèn-Ponce ◽  
Julie Earl ◽  
Maria Teresa Salazar Lopez ◽  
Celia Calcedo ◽  
Reyes Ferreiro ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Cancer Registry ◽  
Familial Pancreatic Cancer

Tu1348 - Diagnostic Yield of Pancreatic Cancer Screening in High-Risk Individuals: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 154 (6) ◽  
pp. S-938-S-939
Author(s):  
Juan E. Corral ◽  
Karl Mareth ◽  
Douglas L. Riegert-Johnson ◽  
Ananya Das ◽  
Michael B. Wallace
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Cancer Screening ◽  
High Risk ◽  
Diagnostic Yield ◽  
Meta Analysis ◽  
Pancreatic Cancer Screening

scholarly journals Genomic Features and Clinical Management of Patients with Hereditary Pancreatic Cancer Syndromes and Familial Pancreatic Cancer

2019 ◽  
Vol 20 (3) ◽  
pp. 561 ◽  
Author(s):  
Akihiro Ohmoto ◽  
Shinichi Yachida ◽  
Chigusa Morizane
Keyword(s):  
Pancreatic Cancer ◽  
Checkpoint Inhibitors ◽  
Susceptibility Gene ◽  
Treatment Strategies ◽  
Familial Pancreatic Cancer ◽  
Cancer Syndrome ◽  
Increased Risk ◽  
Clinical Benefits ◽  
Surveillance Programs ◽  
Cancer Syndromes

Pancreatic cancer (PC) is one of the most devastating malignancies; it has a 5-year survival rate of only 9%, and novel treatment strategies are urgently needed. While most PC cases occur sporadically, PC associated with hereditary syndromes or familial PC (FPC; defined as an individual having two or more first-degree relatives diagnosed with PC) accounts for about 10% of cases. Hereditary cancer syndromes associated with increased risk for PC include Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma, familial adenomatous polyposis, Lynch syndrome and hereditary breast and ovarian cancer syndrome. Next-generation sequencing of FPC patients has uncovered new susceptibility genes such as PALB2 and ATM, which participate in homologous recombination repair, and further investigations are in progress. Previous studies have demonstrated that some sporadic cases that do not fulfil FPC criteria also harbor similar mutations, and so genomic testing based on family history might overlook some susceptibility gene carriers. There are no established screening procedures for high-risk unaffected cases, and it is not clear whether surveillance programs would have clinical benefits. In terms of treatment, poly (ADP-ribose) polymerase inhibitors for BRCA-mutated cases or immune checkpoint inhibitors for mismatch repair deficient cases are promising, and clinical trials of these agents are underway.

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