Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield ...and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in
.
Prospectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound.
Three hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia.
This long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in
. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival.
MRI surveillance in a cohort of CDKN2A-p16-Leiden mutation carriers with a 20% lifetime risk of PDAC led to increased resection rates and improved survival. Patients with screen-detected PDAC were ...evaluated for main pancreatic duct (MPD) abnormalities in this retrospective review.
Since 2000 annual MRI and optional EUS was performed in mutation carriers. Data of patients with screen-detected PDAC was collected on gender, age at diagnosis, site of tumor, size, outcome of surgery, pathology findings and survival. All MRIs were re-evaluated for MPD abnormalities.
23 PDAC were detected in 22 (10%) of 217 mutation carriers, 10 (45%) males and 12 (55%) females. The mean age at diagnosis was 59.8 years (range 39.2–74.3 years). Revision of the MRI/MRCP revealed a lesion and dilatation of the MPD in 8 of the 22 patients. In 5 of 7 patients with PDAC detected during follow-up, the previous MRI showed MPD dilatation without evidence of tumor. The mean size of PDAC was 12.3 mm (range 5–19 mm). All tumors were resectable.
MPD dilation is common in patients with screen-detected PDAC. Abnormalities on MRI during surveillance of high-risk individuals requires intense follow-up or prompt treatment, as early treatment results in a better prognosis.
Background
CDKN2A‐p16‐Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis.
Objective
...To assess the cost‐effectiveness of surveillance, as compared to no surveillance.
Methods
In 2000, a surveillance program was initiated at Leiden University Medical Center with annual MRI and optional endoscopic ultrasound. Data were collected on the resection rate of screen‐detected tumors and on survival. The Kaplan–Meier method and a parametric cure model were used to analyze and compare survival. Based on the surveillance and survival data from the screening program, a state‐transition model was constructed to estimate lifelong outcomes.
Results
A total of 347 mutation carriers participated in the surveillance program. PDAC was detected in 31 patients (8.9%) and the tumor could be resected in 22 patients (71.0%). Long‐term cure among patients with resected PDAC was estimated at 47.1% (p < 0.001). The surveillance program was estimated to reduce mortality from PDAC by 12.1% and increase average life expectancy by 2.10 years. Lifelong costs increased by €13,900 per patient, with a cost‐utility ratio of €14,000 per quality‐adjusted life year gained. For annual surveillance to have an acceptable cost‐effectiveness in other settings, lifetime PDAC risk needs to be 10% or higher.
Conclusion
The tumor could be resected in most patients with a screen‐detected PDAC. These patients had considerably better survival and as a result annual surveillance was found to be cost‐effective.
CDKN2A-p16-Leiden mutation carriers have a substantial risk of developing pancreatic ductal adenocarcinoma (PDAC). One of the main clinical features of hereditary cancer is the development of ...multiple cancers. Since 2000, we have run a surveillance program for CDKN2A-p16-Leiden mutation carriers. The patients are offered a yearly MRI with optionally endoscopic ultrasound. In patients with a confirmed lesion, usually, a partial resection of the pancreas is recommended. A total of 18 PDAC (8.3%) were detected in 218 mutation carriers. In this report, we describe two CDKN2A-p16-Leiden patients with a synchronous and metachronous PDAC. Including two previously-reported cases, we identified four patients with multiple PDAC: two of 18 patients within the surveillance program (11%) and two patients with a proven CDKN2A-p16-Leiden mutation not participating in the surveillance program. In conclusion, this study demonstrated a high risk of developing multiple PDAC in CDKN2A-p16-Leiden mutation carriers. After detecting a primary tumor, it is very important to exclude the presence of a second synchronous tumor. Moreover, after a partial pancreatectomy for PDAC, close surveillance is necessary. In view of the current findings, offering a total pancreatectomy might be an appropriate option in patients with an early PDAC.
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mutation carriers have a 20% to 25% risk of developing pancreatic ductal adenocarcinoma (PDAC). Better understanding of the natural course of PDAC might allow the surveillance protocol to be ...improved. The aims of the study were to evaluate the role of cystic precursor lesions in the development of PDAC and to assess the growth rate. In 2000, a surveillance program was initiated, consisting of annual MRI in carriers of a
mutation. The study cohort included 204 (42% male) patients. Cystic precursor lesions were found in 52 (25%) of 204 mutation carriers. Five (9.7%) of 52 mutation carriers with cystic lesions and 8 (7.0%) of 114 mutation carriers without cystic lesions developed PDAC (
= 0.56). Three of 6 patients with a cystic lesion of ≥10 mm developed PDAC. The median size of all incident PDAC detected between 9 and 12 months since the previous normal MRI was 15 mm, suggesting an annual growth rate of about 15 mm/year. In conclusion, our findings show that patients with and without a cystic lesions have a similar risk of PDAC. However, cystic precursor lesions between 10 and 20 mm increase the risk of PDAC substantially. In view of the large size of the screen-detected tumors, a shorter interval of screening might be recommended for all patients.
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In 3–5 % of all cases of pancreatic ductal adenocarcinoma (PDAC), hereditary factors influence etiology. While surveillance of high-risk individuals may improve the prognosis, this study describes ...two very different outcomes in patients with screen-detected lesions. In 2000, a surveillance program of carriers of a
CDKN2A/p16
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Leiden
-mutation consisting of annual MRI was initiated. Patients with a suspected pancreatic lesion undergo CT-scan and Endoscopic Ultrasound, and surgery is offered when a lesion is confirmed. In 2015, two patients with a screen-detected solid lesion were identified. In both patients, lesions were visible on MRI and CT scan, while the EUS was unremarkable. Surgical resection of the head of the pancreas resulted in nearly fatal complications in the first patient. This patient was shown to have a benign lesion. In contrast, timely identification of an early cancer in the second patient was accompanied by an uneventful postoperative course. These cases underline the risks inherent to a PDAC prevention program. All patients should be fully informed about the possible outcomes before joining a surveillance program.
Background
Widespread abdominal imaging has led to a substantial increase in the detection of incidentalomas. Currently, an increasing number of centers offer surveillance of the pancreas to ...individuals at high risk (IARs) of pancreatic ductal adenocarcinoma (PDAC).
Objective
The aims of this study were to evaluate the frequency and type of incidental findings in a magnetic resonance imaging (MRI)-based surveillance program for IARs for PDAC, and to discuss the benefit of detecting these lesions.
Methods
The outcome of MRI screening was reviewed in 568 individuals from three long-term pancreas surveillance programs conducted at three large European expert centers. All MRIs were studied in detail for the presence of incidental lesions.
Results
The most common lesions were liver cysts, renal cysts and liver hemangioma, which together comprised 75% of all lesions. Only five (0.9%) patients underwent surgery for a benign lesion. Cancer was detected in 11 patients (1.9%); early detection of tumors was beneficial in at least five cases.
Conclusion
The present study demonstrates that extrapancreatic incidentaloma is a common finding in IARs for PDAC, but rarely requires additional treatment. CDKN2A-p16-Leiden mutation carriers were the only patient group found to harbor a substantial number of cancers, and detection resulted in benefit in several cases.
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate ...detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.
Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer FPC) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.
Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.
Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.
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