Pub Date : 2024-08-01Epub Date: 2024-06-06DOI: 10.1007/s10689-024-00404-0
Hans Fa Vasen, Marcia Irene Canto, Michael Goggins
In the 1990s, as prevention became a central strategy in the battle against cancer and the molecular genetics revolution uncovered the genetic basis of numerous hereditary cancer syndromes, there were no options available for patients at increased risk of developing pancreatic cancer. When surveillance efforts for those at familial and hereditary risk of pancreatic cancer emerged in the late 1990s, it was uncertain if early detection was achievable.In this introduction to the special issue, we offer an overview of the history of surveillance for pancreatic cancer, including the first reports of familial pancreatic cancer in the medical literature, the initial results of surveillance in the United States and the initiation of surveillance programs for hereditary pancreatic cancer in the Netherlands.This special issue features a collection of 18 articles written by prominent experts in the field, focusing specifically on refining surveillance methodologies with the primary objective of improving care of high-risk individuals. Several reviews in this collection highlight improved survival rates associated with pancreas surveillance, underlying the potential of early detection and improved management in the continuing fight against pancreatic cancer.
{"title":"Twenty-five years of surveillance for familial and hereditary pancreatic ductal adenocarcinoma: Historical perspectives and introduction to the special issue.","authors":"Hans Fa Vasen, Marcia Irene Canto, Michael Goggins","doi":"10.1007/s10689-024-00404-0","DOIUrl":"10.1007/s10689-024-00404-0","url":null,"abstract":"<p><p>In the 1990s, as prevention became a central strategy in the battle against cancer and the molecular genetics revolution uncovered the genetic basis of numerous hereditary cancer syndromes, there were no options available for patients at increased risk of developing pancreatic cancer. When surveillance efforts for those at familial and hereditary risk of pancreatic cancer emerged in the late 1990s, it was uncertain if early detection was achievable.In this introduction to the special issue, we offer an overview of the history of surveillance for pancreatic cancer, including the first reports of familial pancreatic cancer in the medical literature, the initial results of surveillance in the United States and the initiation of surveillance programs for hereditary pancreatic cancer in the Netherlands.This special issue features a collection of 18 articles written by prominent experts in the field, focusing specifically on refining surveillance methodologies with the primary objective of improving care of high-risk individuals. Several reviews in this collection highlight improved survival rates associated with pancreas surveillance, underlying the potential of early detection and improved management in the continuing fight against pancreatic cancer.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-11DOI: 10.1007/s10689-024-00395-y
Hiroyuki Matsubayashi, Chigusa Morizane
As in Western countries, familial pancreatic cancer accounts for 5-7% of pancreatic cancer (PC) in Japan. Opportunities for diagnosing hereditary pancreatic cancer (HPC) are increasing owing to the coverage of companion diagnostics and cancer genomic profiling by national health insurance in patients with unresectable or recurrent PC refractory to standard chemotherapies. HPC is recognized in 7% of PCs and 15% of familial pancreatic cancer, including germline variants of BRCA1/2, ATM, PALB2, APC, and mismatch repair genes. Individuals with 5-fold or greater inherited risks of PC are recommended to undergo pancreatic surveillance according to Japanese guidelines. The imaging modalities for this surveillance include endoscopic ultrasound, magnetic resonance cholangiopancreatography, abdominal ultrasound, and enhanced computed tomography. Currently, a nationwide prospective surveillance study is ongoing in Japan. Platinum-based chemotherapy is an effective pancreatic cancer treatment in patients with variants of homologous recombination repair genes (BRCA1/2 and PALB2); however, the use of platinum regimens solely based on familial/personal cancer history remains controversial. The efficacy of olaparib maintenance therapy, as confirmed by the POLO study, has significantly impacted the clinical treatment of advanced PC patients in Japan. Since the initiation of precision cancer medicine in 2019, genetic medicine for PC patients has expanded in Japan.
与西方国家一样,在日本,家族性胰腺癌占胰腺癌(PC)的 5-7%。由于国家医疗保险覆盖了标准化疗难治性或复发性胰腺癌患者的辅助诊断和癌症基因组分析,诊断遗传性胰腺癌(HPC)的机会正在增加。在 7% 的 PC 和 15% 的家族性胰腺癌中发现了 HPC,包括 BRCA1/2、ATM、PALB2、APC 和错配修复基因的种系变异。根据日本的指南,建议胰腺癌遗传风险为 5 倍或更高的患者接受胰腺监测。这种监测的成像模式包括内镜超声、磁共振胰胆管造影、腹部超声和增强型计算机断层扫描。目前,日本正在进行一项全国性的前瞻性监测研究。对于存在同源重组修复基因(BRCA1/2 和 PALB2)变异的患者,以铂为基础的化疗是一种有效的胰腺癌治疗方法;然而,仅根据家族/个人癌症病史使用铂方案仍存在争议。POLO 研究证实了奥拉帕利维持治疗的疗效,这对日本晚期 PC 患者的临床治疗产生了重大影响。自 2019 年启动癌症精准医疗以来,针对 PC 患者的基因医疗在日本得到了扩展。
{"title":"Familial and hereditary pancreatic cancer in Japan.","authors":"Hiroyuki Matsubayashi, Chigusa Morizane","doi":"10.1007/s10689-024-00395-y","DOIUrl":"10.1007/s10689-024-00395-y","url":null,"abstract":"<p><p>As in Western countries, familial pancreatic cancer accounts for 5-7% of pancreatic cancer (PC) in Japan. Opportunities for diagnosing hereditary pancreatic cancer (HPC) are increasing owing to the coverage of companion diagnostics and cancer genomic profiling by national health insurance in patients with unresectable or recurrent PC refractory to standard chemotherapies. HPC is recognized in 7% of PCs and 15% of familial pancreatic cancer, including germline variants of BRCA1/2, ATM, PALB2, APC, and mismatch repair genes. Individuals with 5-fold or greater inherited risks of PC are recommended to undergo pancreatic surveillance according to Japanese guidelines. The imaging modalities for this surveillance include endoscopic ultrasound, magnetic resonance cholangiopancreatography, abdominal ultrasound, and enhanced computed tomography. Currently, a nationwide prospective surveillance study is ongoing in Japan. Platinum-based chemotherapy is an effective pancreatic cancer treatment in patients with variants of homologous recombination repair genes (BRCA1/2 and PALB2); however, the use of platinum regimens solely based on familial/personal cancer history remains controversial. The efficacy of olaparib maintenance therapy, as confirmed by the POLO study, has significantly impacted the clinical treatment of advanced PC patients in Japan. Since the initiation of precision cancer medicine in 2019, genetic medicine for PC patients has expanded in Japan.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-01DOI: 10.1007/s10689-024-00401-3
A M Onnekink, D C F Klatte, J E van Hooft, S H van den Berg, S M S van der Zwaan, R van Doorn, S C H Hinnen, T P Potjer, E M A Bleiker, M E van Leerdam
Individuals with a germline CDKN2A pathogenic variant (PV) have a highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward genetic testing, family planning, and preimplantation genetic testing (PGT) in confirmed CDKN2A PV carriers and individuals with a 50% risk of the PV (at-risk carriers) using of a one-time questionnaire.A total of 537 individuals were screened for eligibility, of whom 208 of 366 (57%) confirmed carriers (56% female, median age 54 years [IQR 46-63]) and 39 of 171 (23%) at-risk carriers (59% female, median age of 26 years [IQR 22-32]) participated in the study. Primary motivations for genetic testing were to gain control over their personal and children's cancer risk, as well as increasing cancer surveillance practices. In contrast, concerns about obtaining a mortgage and life insurance were frequently cited as reasons for postponing genetic testing. Family planning decisions remained largely unaffected in both confirmed and at-risk carriers; however, the majority of confirmed carriers were still unaware of their familial or personal cancer risk when starting a family. More than 60% of the participants were unfamiliar with PGT and only a minority (19% of confirmed carriers and 10% of at-risk carriers) would be open to considering PGT as a reproductive option. This study found different attitudes toward genetic testing, family planning, and PGT among individuals affected by the CDKN2A PV. Understanding these different attitudes can help clinicians to address the complexities surrounding these issues, especially for younger individuals facing difficult decisions about the timing of genetic testing, family planning, and the potential use of assisted reproductive options.
{"title":"Attitudes toward genetic testing, family planning and preimplantation genetic testing in families with a germline CDKN2A pathogenic variant.","authors":"A M Onnekink, D C F Klatte, J E van Hooft, S H van den Berg, S M S van der Zwaan, R van Doorn, S C H Hinnen, T P Potjer, E M A Bleiker, M E van Leerdam","doi":"10.1007/s10689-024-00401-3","DOIUrl":"10.1007/s10689-024-00401-3","url":null,"abstract":"<p><p>Individuals with a germline CDKN2A pathogenic variant (PV) have a highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward genetic testing, family planning, and preimplantation genetic testing (PGT) in confirmed CDKN2A PV carriers and individuals with a 50% risk of the PV (at-risk carriers) using of a one-time questionnaire.A total of 537 individuals were screened for eligibility, of whom 208 of 366 (57%) confirmed carriers (56% female, median age 54 years [IQR 46-63]) and 39 of 171 (23%) at-risk carriers (59% female, median age of 26 years [IQR 22-32]) participated in the study. Primary motivations for genetic testing were to gain control over their personal and children's cancer risk, as well as increasing cancer surveillance practices. In contrast, concerns about obtaining a mortgage and life insurance were frequently cited as reasons for postponing genetic testing. Family planning decisions remained largely unaffected in both confirmed and at-risk carriers; however, the majority of confirmed carriers were still unaware of their familial or personal cancer risk when starting a family. More than 60% of the participants were unfamiliar with PGT and only a minority (19% of confirmed carriers and 10% of at-risk carriers) would be open to considering PGT as a reproductive option. This study found different attitudes toward genetic testing, family planning, and PGT among individuals affected by the CDKN2A PV. Understanding these different attitudes can help clinicians to address the complexities surrounding these issues, especially for younger individuals facing difficult decisions about the timing of genetic testing, family planning, and the potential use of assisted reproductive options.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-11DOI: 10.1007/s10689-024-00394-z
Bas Boekestijn, Shirin Feshtali, Hans Vasen, Monique E van Leerdam, Bert A Bonsing, J Sven D Mieog, Martin N Wasser
Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease and especially patients with lesions smaller than 10 mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.
{"title":"Screening for pancreatic cancer in high-risk individuals using MRI: optimization of scan techniques to detect small lesions.","authors":"Bas Boekestijn, Shirin Feshtali, Hans Vasen, Monique E van Leerdam, Bert A Bonsing, J Sven D Mieog, Martin N Wasser","doi":"10.1007/s10689-024-00394-z","DOIUrl":"10.1007/s10689-024-00394-z","url":null,"abstract":"<p><p>Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease and especially patients with lesions smaller than 10 mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-25DOI: 10.1007/s10689-024-00392-1
Louise Wang, Rachel Levinson, Catherine Mezzacappa, Bryson W Katona
Individuals with hereditary pancreatic cancer risk include high risk individuals (HRIs) with germline genetic susceptibility to pancreatic cancer (PC) and/or a strong family history of PC. Previously, studies have shown that PC surveillance in HRIs can downstage PC diagnosis and extend survival leading to pancreatic surveillance being recommended for certain HRIs. However, the optimal surveillance strategy remains uncertain, including which modalities should be used for surveillance, how frequently should surveillance be performed, and which sub-groups of HRIs should undergo surveillance. Additionally, in the ideal world PC surveillance should also be cost-effective. Cost-effectiveness analysis is a valuable tool that can consider the costs, potential health benefits, and risks among various PC surveillance strategies. In this review, we summarize the cost-effectiveness of various PC surveillance strategies for HRIs for hereditary pancreatic cancer and provide potential avenues for future work in this field. Additionally, we include cost-effectiveness studies among individuals with new-onset diabetes (NoD), a high-risk group for sporadic PC, as a comparison.
有遗传性胰腺癌风险的人包括对胰腺癌(PC)有种系遗传易感性和/或有胰腺癌家族史的高危人群(HRIs)。以前的研究表明,对高危人群进行 PC 监测可以降低 PC 诊断的晚期并延长生存期,因此建议对某些高危人群进行胰腺监测。然而,最佳的监测策略仍不确定,包括监测应采用哪些方式、监测的频率以及哪些 HRI 亚群应接受监测。此外,在理想情况下,PC 监测还应具有成本效益。成本效益分析是一种非常有价值的工具,它可以考虑各种 PC 监测策略的成本、潜在健康益处和风险。在本综述中,我们总结了针对遗传性胰腺癌 HRIs 的各种 PC 监测策略的成本效益,并提供了该领域未来工作的潜在途径。此外,我们还纳入了对散发性胰腺癌高危人群--新发糖尿病(NoD)患者的成本效益研究,作为对比。
{"title":"Review of the cost-effectiveness of surveillance for hereditary pancreatic cancer.","authors":"Louise Wang, Rachel Levinson, Catherine Mezzacappa, Bryson W Katona","doi":"10.1007/s10689-024-00392-1","DOIUrl":"10.1007/s10689-024-00392-1","url":null,"abstract":"<p><p>Individuals with hereditary pancreatic cancer risk include high risk individuals (HRIs) with germline genetic susceptibility to pancreatic cancer (PC) and/or a strong family history of PC. Previously, studies have shown that PC surveillance in HRIs can downstage PC diagnosis and extend survival leading to pancreatic surveillance being recommended for certain HRIs. However, the optimal surveillance strategy remains uncertain, including which modalities should be used for surveillance, how frequently should surveillance be performed, and which sub-groups of HRIs should undergo surveillance. Additionally, in the ideal world PC surveillance should also be cost-effective. Cost-effectiveness analysis is a valuable tool that can consider the costs, potential health benefits, and risks among various PC surveillance strategies. In this review, we summarize the cost-effectiveness of various PC surveillance strategies for HRIs for hereditary pancreatic cancer and provide potential avenues for future work in this field. Additionally, we include cost-effectiveness studies among individuals with new-onset diabetes (NoD), a high-risk group for sporadic PC, as a comparison.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141096845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-02-06DOI: 10.1007/s10689-024-00359-2
Michael J Pflüger, Lodewijk A A Brosens, Ralph H Hruban
Infiltrating ductal adenocarcinoma of the pancreas, referred to here as "pancreatic cancer," is one of the deadliest of all of the solid malignancies. The five-year survival rate in the United States for individuals diagnosed today with pancreatic cancer is a dismal 12%. Many invasive cancers, including pancreatic cancer, however, arise from histologically and genetically well-characterized precursor lesions, and these precancers are curable. Precursor lesions therefore are an attractive target for early detection and treatment. This is particularly true for individuals with an increased risk of developing invasive cancer, such as individuals with a strong family history of pancreatic cancer, and individuals with a germline variant known to increase the risk of developing pancreatic cancer. There is therefore a need to understand the precursor lesions that can give rise to invasive pancreatic cancer in these individuals.
{"title":"Precursor lesions in familial and hereditary pancreatic cancer.","authors":"Michael J Pflüger, Lodewijk A A Brosens, Ralph H Hruban","doi":"10.1007/s10689-024-00359-2","DOIUrl":"10.1007/s10689-024-00359-2","url":null,"abstract":"<p><p>Infiltrating ductal adenocarcinoma of the pancreas, referred to here as \"pancreatic cancer,\" is one of the deadliest of all of the solid malignancies. The five-year survival rate in the United States for individuals diagnosed today with pancreatic cancer is a dismal 12%. Many invasive cancers, including pancreatic cancer, however, arise from histologically and genetically well-characterized precursor lesions, and these precancers are curable. Precursor lesions therefore are an attractive target for early detection and treatment. This is particularly true for individuals with an increased risk of developing invasive cancer, such as individuals with a strong family history of pancreatic cancer, and individuals with a germline variant known to increase the risk of developing pancreatic cancer. There is therefore a need to understand the precursor lesions that can give rise to invasive pancreatic cancer in these individuals.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-23DOI: 10.1007/s10689-024-00397-w
Cristina-Marianini-Rios, María E Castillo Sanchez, Ana García García de Paredes, Mercedes Rodríguez, Emma Barreto, Jorge Villalón López, Raquel Fuentes, María Muñoz Beltrán, Alfonso Sanjuanbenito, Eduardo Lobo, Alejandra Caminoa, Ignacio Ruz-Caracuel, Sergio López Durán, José Ramón Foruny Olcina, Javier Blázquez, Enrique Vázquez Sequeros, Alfredo Carrato, Jose Carlos Martínez Ávila, Julie Earl
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the Western world. The number of diagnosed cases and the mortality rate are almost equal as the majority of patients present with advanced disease at diagnosis. Between 4 and 10% of pancreatic cancer cases have an apparent hereditary background, known as hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC), when the genetic basis is unknown. Surveillance of high-risk individuals (HRI) from these families by imaging aims to detect PDAC at an early stage to improve prognosis. However, the genetic basis is unknown in the majority of HRIs, with only around 10-13% of families carrying known pathogenic germline mutations. The aim of this study was to assess an individual's genetic cancer risk based on sex and personal and family history of cancer. The Best Linear Unbiased Prediction (BLUP) methodology was used to estimate an individual's predicted risk of developing cancer during their lifetime. The model uses different demographic factors in order to estimate heritability. A reliable estimation of heritability for pancreatic cancer of 0.27 on the liability scale, and 0.07 at the observed data scale as obtained, which is different from zero, indicating a polygenic inheritance pattern of PDAC. BLUP was able to correctly discriminate PDAC cases from healthy individuals and those with other cancer types. Thus, providing an additional tool to assess PDAC risk HRI with an assumed genetic predisposition in the absence of known pathogenic germline mutations.
{"title":"The best linear unbiased prediction (BLUP) method as a tool to estimate the lifetime risk of pancreatic ductal adenocarcinoma in high-risk individuals with no known pathogenic germline variants.","authors":"Cristina-Marianini-Rios, María E Castillo Sanchez, Ana García García de Paredes, Mercedes Rodríguez, Emma Barreto, Jorge Villalón López, Raquel Fuentes, María Muñoz Beltrán, Alfonso Sanjuanbenito, Eduardo Lobo, Alejandra Caminoa, Ignacio Ruz-Caracuel, Sergio López Durán, José Ramón Foruny Olcina, Javier Blázquez, Enrique Vázquez Sequeros, Alfredo Carrato, Jose Carlos Martínez Ávila, Julie Earl","doi":"10.1007/s10689-024-00397-w","DOIUrl":"10.1007/s10689-024-00397-w","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the Western world. The number of diagnosed cases and the mortality rate are almost equal as the majority of patients present with advanced disease at diagnosis. Between 4 and 10% of pancreatic cancer cases have an apparent hereditary background, known as hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC), when the genetic basis is unknown. Surveillance of high-risk individuals (HRI) from these families by imaging aims to detect PDAC at an early stage to improve prognosis. However, the genetic basis is unknown in the majority of HRIs, with only around 10-13% of families carrying known pathogenic germline mutations. The aim of this study was to assess an individual's genetic cancer risk based on sex and personal and family history of cancer. The Best Linear Unbiased Prediction (BLUP) methodology was used to estimate an individual's predicted risk of developing cancer during their lifetime. The model uses different demographic factors in order to estimate heritability. A reliable estimation of heritability for pancreatic cancer of 0.27 on the liability scale, and 0.07 at the observed data scale as obtained, which is different from zero, indicating a polygenic inheritance pattern of PDAC. BLUP was able to correctly discriminate PDAC cases from healthy individuals and those with other cancer types. Thus, providing an additional tool to assess PDAC risk HRI with an assumed genetic predisposition in the absence of known pathogenic germline mutations.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-16DOI: 10.1007/s10689-024-00388-x
Julie Earl, Raquel Fuentes, María E Castillo Sanchez, Ana García García de Paredes, María Muñoz, Alfonso Sanjuanbenito, Eduardo Lobo, Alejandra Caminoa, Mercedes Rodríguez, Emma Barreto, Jorge Villalón López, Ignacio Ruz-Caracuel, Sergio López Durán, José Ramón Foruny Olcina, Bárbara Luna Sánchez, Sonia Camaño Páez, Ana Torres, Javier Blázquez, Enrique Vázquez Sequeros, Alfredo Carrato
The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29-83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy.
{"title":"The Spanish Familial Pancreatic Cancer Registry (PANGENFAM): a decade follow-up of individuals at high-risk for pancreatic cancer.","authors":"Julie Earl, Raquel Fuentes, María E Castillo Sanchez, Ana García García de Paredes, María Muñoz, Alfonso Sanjuanbenito, Eduardo Lobo, Alejandra Caminoa, Mercedes Rodríguez, Emma Barreto, Jorge Villalón López, Ignacio Ruz-Caracuel, Sergio López Durán, José Ramón Foruny Olcina, Bárbara Luna Sánchez, Sonia Camaño Páez, Ana Torres, Javier Blázquez, Enrique Vázquez Sequeros, Alfredo Carrato","doi":"10.1007/s10689-024-00388-x","DOIUrl":"10.1007/s10689-024-00388-x","url":null,"abstract":"<p><p>The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29-83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-11DOI: 10.1007/s10689-024-00389-w
Nicolette Juliana Rodriguez, Sapna Syngal
Among individuals with pancreatic ductal adenocarcinoma (PDAC) 5-10% have a pathogenic germline variant (PGV) in a PDAC susceptibility gene. Guidelines recommend genetic testing among all individuals with PDAC. Additionally, at-risk relatives of PDAC patients benefit from their own genetic education, risk assessment, and testing. Multigene panel testing (MGPT) can identify individuals with inherited cancer risk who can benefit from early cancer surveillance and risk reduction strategies. This manuscript discusses various healthcare delivery models for MGPT including traditional in-person genetic counseling, novel integrated in-person infrastructures, telemedicine genetics care via telephone- or video-visits and direct-to-consumer testing. Barriers and facilitators to care on the individual, provider, and system level are also outlined including specific considerations for historically marginalized communities.
{"title":"Expanding access to genetic testing for pancreatic cancer.","authors":"Nicolette Juliana Rodriguez, Sapna Syngal","doi":"10.1007/s10689-024-00389-w","DOIUrl":"10.1007/s10689-024-00389-w","url":null,"abstract":"<p><p>Among individuals with pancreatic ductal adenocarcinoma (PDAC) 5-10% have a pathogenic germline variant (PGV) in a PDAC susceptibility gene. Guidelines recommend genetic testing among all individuals with PDAC. Additionally, at-risk relatives of PDAC patients benefit from their own genetic education, risk assessment, and testing. Multigene panel testing (MGPT) can identify individuals with inherited cancer risk who can benefit from early cancer surveillance and risk reduction strategies. This manuscript discusses various healthcare delivery models for MGPT including traditional in-person genetic counseling, novel integrated in-person infrastructures, telemedicine genetics care via telephone- or video-visits and direct-to-consumer testing. Barriers and facilitators to care on the individual, provider, and system level are also outlined including specific considerations for historically marginalized communities.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-03-05DOI: 10.1007/s10689-024-00363-6
J-Matthias Löhr, Daniel Öhlund, Emma Söreskog, Emil Andersson, Miroslav Vujasinovic, Niklas Zethraeus, Malin Sund
Screening of the general population for cancer is a matter of primary prevention reducing the burden of disease. Whilst this is successful for several cancers including breast, colon and prostate, the situation to screen and hence prevent pancreatic cancer is different. The organ is not as accessible to simple physical exam or biological samples (fecal or blood test). Neither exists a blood test such as PSA that is cost-effective. Reviewing the evidence from screening risk groups for pancreatic cancer, one must conclude that there is no rational at present to screen the general population, for a lack of appropriate tests.
{"title":"Can our experience with surveillance for inherited pancreatic cancer help to identify early pancreatic cancer in the general population?","authors":"J-Matthias Löhr, Daniel Öhlund, Emma Söreskog, Emil Andersson, Miroslav Vujasinovic, Niklas Zethraeus, Malin Sund","doi":"10.1007/s10689-024-00363-6","DOIUrl":"10.1007/s10689-024-00363-6","url":null,"abstract":"<p><p>Screening of the general population for cancer is a matter of primary prevention reducing the burden of disease. Whilst this is successful for several cancers including breast, colon and prostate, the situation to screen and hence prevent pancreatic cancer is different. The organ is not as accessible to simple physical exam or biological samples (fecal or blood test). Neither exists a blood test such as PSA that is cost-effective. Reviewing the evidence from screening risk groups for pancreatic cancer, one must conclude that there is no rational at present to screen the general population, for a lack of appropriate tests.</p>","PeriodicalId":12336,"journal":{"name":"Familial Cancer","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}