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

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.

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Spanish national hereditary pancreatic cancer registry (PanFAM).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e12033 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e12033-e12033

Author(s):

Carmen Guillen-Ponce ◽

Evelina Mocci ◽

Julie Earl ◽

Carmen T Guerrero ◽

Maria Celia Calcedo ◽

...

Keyword(s):

Pancreatic Cancer ◽

High Risk ◽

Screening Program ◽

Epidemiological Data ◽

Screening Methods ◽

Familial Pancreatic Cancer ◽

Inherited Predisposition ◽

Screening Study ◽

Age Of Diagnosis ◽

Breast And Prostate Cancer

e12033 Background: Inherited predisposition to Pancreatic Cancer (PC) corresponds 10% of all cases and includes members of families affected with hereditary cancer syndromes as Familial Pancreatic Cancer (FPC), Peutz-Jeghers, familial melanoma, hereditary breast and ovarian cancer, hereditary pancreatitis. An inherited predisposition in early onset PC (≤ 50 years) has also been suggested. We report preliminary data on PanFAM patients and screening of high risk individuals. Methods: PamFAM is a part of the European PANGEN PC case/control study of hereditary PC, co-ordinated by the Ramón y Cajal (RC) hospital and the Spanish National Cancer Research Center, with 16 participating hospitals. All families with clinical evidence of an inherited PC syndrome were recruited and multi-generational pedigrees were constructed. Cancer diagnoses were confirmed, when possible, by review of medical records. Blood samples and epidemiological data were collected for all participating family members. A screening program for early detection of PC, based on endoscopic ultrasound (EUS), CT and circulating tumour cells (CTCs) was offered to high risk individuals. Results: Of 505 Spanish PCs collected by PANGEN, 31 (~6%) were FPC cases; 18 (58%) revealed only PC and the remaining showed clustering with other tumor types, gastric cancer was the most common (13%). Among FPC families, 3 had 3 cases of PC and the remaining had 2 cases. The mean age of diagnosis was 67 years (range 47-85), 20 male and 11 female. Four FPCs were previously diagnosed with cancer (Hodgkin lymphoma, breast and prostate cancer) and 3 with acute pancreatitis. 37 PCs with no family history of cancer were diagnosed at the age of 50 years or earlier (mean 45, range 30-50), 18 male and 19 female. Other 27 eligible families were recruited by RyC hospital, 8 (30%) with FPC and 3 (11%) with PC ≤ 50 years. A cohort of 61 high risk individuals participes in the screening study: 3 had abnormal EUS, 1 a benign pancreatic node and 1 a renal angiolipoma; one young man had 2 CTCs. Conclusions: PanFAM is the first registry in Spain collecting hereditary PC cases and it represents an important resource to identify underlying gene defects and to the development of screening methods precursor lesions detection in high risk individuals.

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Clinical importance of Familial Pancreatic Cancer Registry in Japan: a report from kick-off meeting at International Symposium on Pancreas Cancer 2012

Journal of Hepato-Biliary-Pancreatic Sciences ◽

10.1007/s00534-013-0611-5 ◽

2013 ◽

Vol 20 (6) ◽

pp. 557-566 ◽

Cited By ~ 10

Author(s):

Keita Wada ◽

Kyoichi Takaori ◽

L. William Traverso ◽

Ralph H. Hruban ◽

Toru Furukawa ◽

...

Keyword(s):

Pancreatic Cancer ◽

International Symposium ◽

Cancer Registry ◽

Pancreas Cancer ◽

Clinical Importance ◽

Familial Pancreatic Cancer

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Japanese Familial Pancreatic Cancer Registry with the aim to early detection of pancreatic cancer

Suizo ◽

10.2958/suizo.32.23 ◽

2017 ◽

Vol 32 (1) ◽

pp. 23-29 ◽

Cited By ~ 2

Author(s):

Chigusa MORIZANE ◽

Masayuki KITANO ◽

Susumu HIJIOKA ◽

Tetsuhide ITO ◽

Terumi KAMISAWA ◽

...

Keyword(s):

Pancreatic Cancer ◽

Early Detection ◽

Cancer Registry ◽

Familial Pancreatic Cancer

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

Gut ◽

10.1136/gutjnl-2020-323611 ◽

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.

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S0025 Patients in Familial Pancreatic Cancer Kindreds Demonstrate Increased High-Risk Radiological Features Compared to Those With Deleterious Germline Variants in a High-Risk Pancreatic Surveillance Program

The American Journal of Gastroenterology ◽

10.14309/01.ajg.0000697984.65963.84 ◽

2020 ◽

Vol 115 (1) ◽

pp. S11-S12

Author(s):

Marlon J. Brewer ◽

Ariel Bar-Mashiah ◽

Anne Aronson ◽

Elizabeth Kessel ◽

Christopher J. DiMaio ◽

...

Keyword(s):

Pancreatic Cancer ◽

High Risk ◽

Surveillance Program ◽

Familial Pancreatic Cancer ◽

Germline Variants ◽

Radiological Features

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Genetic and phenotypic characterization of families with familial pancreatic cancer and screening of high-risk individuals.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.242 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 242-242

Author(s):

Carmen Guillen ◽

Julie Earl ◽

Evelina Mocci ◽

Carme Guerrero ◽

Jose Montans ◽

...

Keyword(s):

Pancreatic Cancer ◽

High Risk ◽

Screening Program ◽

Premalignant Lesions ◽

Phenotypic Characterization ◽

Familial Pancreatic Cancer ◽

Cystic Lesions ◽

Term Survival ◽

Clinical Screening ◽

Partial Pancreatectomy

242 Background: The prognosis of patients diagnosed with Pancreatic Cancer (PC) is dismal with a 5-year survival rate of around 5%. Familial Pancreatic Cancer (FPC) is an autosomal dominant rare syndrome defined as families with two or more first-degree relatives with pancreatic cancer that do not fulfill the criteria of any other inherited tumor syndrome. The Spanish familial pancreatic cancer registry, Pan-Gen-FAM was established in 2009 in order to identify and manage families at high risk of developing PC. Methods: Information on the family history of cancer is collected in order to determine the phenotype of individual families and patients are offered genetic testing of known FPC associated genes pertinent to their familial syndrome. An individualized clinical screening program is devised for the early detection of a pancreatic tumor consisting of periodic monitoring by imaging techniques (EUS and MRI) and the evaluation of minimally-invasive tumor biomarkers approaches including Circulating Tumor Cells (CTC) and circulating free DNA in blood. Results: To date the registry includes 125 individuals representing some 41 families. Of 17 families tested so far BRCA2 germline mutations were detected in 5 families and a BRCA1 mutation in 1 family. 43 individuals underwent clinical screening. More pancreatic abnormalities were found by EUS (41%) than by MRI (31%). The most frequent abnormal findings were parenchymal changes associated with chronic pancreatitis. Eight cystic lesions were identified. One lesion was identified as a well differentiated neuroendocrine tumor and another was shown to have benign cytology and whilst carcinoma was found in a third patient, this patient underwent a subsequent partial pancreatectomy. The remaining patients with cystic lesions are undergoing close clinical observation. Seventy three patients underwent CTC determinations and all patients tested negative. Conclusions: Periodic screening of high risk individuals by EUS and RMI can detect small tumors and premalignant lesions. We hypothesize that these persons will have a higher probability of long-term survival than sporadic cases.

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