Late-Stage Pancreatic Cancer Detected During High-Risk Individual Surveillance: A Systematic Review and Meta-Analysis

Chhoda, Ankit; Vodusek, Ziga; Wattamwar, Kapil; Mukherjee, Eric M.; Gunderson, Craig G.; Grimshaw, Alyssa; Sharma, Anup; Ahuja, Nita; Kastrinos, Fay; Farrell, James J.

doi:10.1053/j.gastro.2021.11.021

Cited by 31 publications

(22 citation statements)

References 43 publications

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“…International Cancer of Pancreas Screening (CAPS) Consortium was then established with the aim of early diagnosis of PC for those with familial risk, and the first consensus conference was held in 2011 (14) with a recent update in 2019 (15). The consensus meeting strongly recommended EUS and MRI as screening modalities due to their high resolution and lack of ionizing radiation although a recent meta-analysis suggested the difficulty of diagnosis of malignant lesions in the early stage (18). Although several studies have reported the usefulness of screening in HRIs (10)(11)(12), these data had been published mainly from Western countries, and data from Asia, such as Japan, are still lacking.…”

Section: Discussionmentioning

confidence: 99%

New Screening System Using Forward-Viewing Radial Endoscopic Ultrasound and Magnetic Resonance Imaging for High-Risk Individuals With Familial History of Pancreatic Cancer

et al. 2022

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Background and AimsAttention is increasingly being paid to family history of pancreatic cancer (PC) as a risk factor for developing PC. It is mandatory to develop a screening system for early detection of PC; however, the relationship between a family history of PC and the incidence of pancreatic abnormalities, such as pancreatic cyst and chronic pancreatitis (CP), in the Japanese population remains unknown.Patients and MethodsIndividuals with a family history of PC were prospectively enrolled in a screening program using forward-viewing radial endoscopic ultrasound (FR-EUS) and magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) as the diagnostic modalities.ResultsIn total, forty-three individuals in 37 families were enrolled (mean age, 54 years). All individuals underwent FR-EUS and MRI with no complications. FR-EUS revealed resectable PC (n = 1, 2.3%), pancreatic cysts (n = 24, 55.8%), intraductal papillary mucinous neoplasm (IPMN; n = 13, 30.2%), and early CP-like appearance (n = 15, 34.9%). The detection rate of early CP-like appearance was significantly higher by EUS than by MRI. Pancreatic cysts and IPMN detected by FR-EUS were significantly correlated to age (≥60 years) and less correlated to men (hazard ratio [HR] 22.4; 95% confidence interval [CI], 2.10–236.0; p < 0.01 and HR 0.092; 95% CI, 0.01–0.83; p = 0.033, respectively). Early CP-like appearance detected by FR-EUS was significantly correlated with men and smoking (HR 5.0; 95% CI, 1.3–19.3; p = 0.02 and HR 4.02; 95% CI, 0.991–16.3; p = 0.05, respectively).ConclusionA screening system using FR-EUS and MRI/MRCP for individuals with a family history of PC was useful for identifying curable PC and pancreatic abnormalities. The incidence of pancreatic cysts, such as IPMN and early CP-like appearance, was also high in the Japanese cohort.

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Section: Discussionmentioning

confidence: 99%

New Screening System Using Forward-Viewing Radial Endoscopic Ultrasound and Magnetic Resonance Imaging for High-Risk Individuals With Familial History of Pancreatic Cancer

et al. 2022

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“…Regarding the latter, recent reports have shown, unfortunately, that incidental PDAC exists and that 12-month surveillance may sometimes be ineffective [57,58]. In addition, a non-negligible amount of PDAC detected within surveillance is diagnosed at an advanced stage, raising the question of whether this surveillance strategy may be tailored according to an individualized risk-profile [59]. If the screening is negative for pancreatic abnormalities, then it should be repeated annually to possibly improve the early identification of PDAC or pre-malignant lesions.…”

Section: Preventative Implicationsmentioning

confidence: 99%

Germline Aberrations in Pancreatic Cancer: Implications for Clinical Care

Casolino

Corbo

Beer

et al. 2022

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis and represents a major public health issue, as both its incidence and mortality are expecting to increase steeply over the next years. Effective screening strategies are lacking, and most patients are diagnosed with unresectable disease precluding the only chance of cure. Therapeutic options for advanced disease are limited, and the treatment paradigm is still based on chemotherapy, with a few rare exceptions to targeted therapies. Germline variants in cancer susceptibility genes—particularly those involved in mechanisms of DNA repair—are emerging as promising targets for PDAC treatment and prevention. Hereditary PDAC is part of the spectrum of several syndromic disorders, and germline testing of PDAC patients has relevant implications for broad cancer prevention. Germline aberrations in BRCA1 and BRCA2 genes are predictive biomarkers of response to poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitor olaparib and platinum-based chemotherapy in PDAC, while mutations in mismatch repair genes identify patients suitable for immune checkpoint inhibitors. This review provides a timely and comprehensive overview of germline aberrations in PDAC and their implications for clinical care. It also discusses the need for optimal approaches to better select patients for PARP inhibitor therapy, novel therapeutic opportunities under clinical investigation, and preclinical models for cancer susceptibility and drug discovery.

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“…On the basis of these early findings, however, multiple professional society guidelines now recommend that EUS-/MRCP-based PDAC surveillance be considered for individuals with PDAC susceptibility gene PGVs and a family history of PDAC, and/or those from familial pancreatic cancer families. 19,23,24 Other recent data, 25,26 however, have demonstrated disappointing rates of advanced-stage PDAC in high-risk individuals undergoing regular EUS-/MRCP-based surveillance, highlighting the importance of long-term outcomes data.…”

mentioning

confidence: 99%

“…Both studies also demonstrate reasonable numbers-needed-to-screen to detect a single PDAC case (70 CDKN2A carriers/y in Klatte et al 7 and 194 high-risk individuals/y in Dbouk et al 27 ). Another more sobering lesson learned from these studies 7,27 and others, 21,25,26 however, is the rapid pace at which PDACs can develop even in high-risk individuals undergoing regular surveillance, including numerous cases of non-stage I PDACs diagnosed within 12 months of prior reassuring imaging. Nonetheless, the encouraging long-term outcomes reported by these two studies 7,27 reinforce guidelines 19,23,24 recommending MRCP-/EUS-based PDAC surveillance for certain individuals with genetic/familial high risk.…”

mentioning

confidence: 99%

Building on More Than 20 Years of Progress in Pancreatic Cancer Surveillance for High-Risk Individuals

Yurgelun

2022

JCO

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Late-Stage Pancreatic Cancer Detected During High-Risk Individual Surveillance: A Systematic Review and Meta-Analysis

Cited by 31 publications

References 43 publications

New Screening System Using Forward-Viewing Radial Endoscopic Ultrasound and Magnetic Resonance Imaging for High-Risk Individuals With Familial History of Pancreatic Cancer

New Screening System Using Forward-Viewing Radial Endoscopic Ultrasound and Magnetic Resonance Imaging for High-Risk Individuals With Familial History of Pancreatic Cancer

Germline Aberrations in Pancreatic Cancer: Implications for Clinical Care

Building on More Than 20 Years of Progress in Pancreatic Cancer Surveillance for High-Risk Individuals

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