Browsing by Author "Klein, Alison P."

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    A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO
    (Springer Nature, 2021) Blackford, Amanda L.; Childs, Erica J.; Porter, Nancy; Petersen, Gloria M.; Rabe, Kari G.; Gallinger, Steven; Borgida, Ayelet; Syngal, Sapna; Cote, Michele L.; Schwartz, Ann G.; Goggins, Michael G.; Hruban, Ralph H.; Parmigiani, Giovanni; Klein, Alison P.; Epidemiology, Richard M. Fairbanks School of Public Health
    Introduction: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. Methods: We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations. Results: BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]). Discussion: The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer.
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    Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases: Workshop Proceedings
    (Wolters Kluwer, 2022) Mastracci, Teresa L.; Apte, Minoti; Amundadottir, Laufey T.; Alvarsson, Alexandra; Artandi, Steven; Bellin, Melena D.; Bernal-Mizrachi, Ernesto; Caicedo, Alejandro; Campbell-Thompson, Martha; Cruz-Monserrate, Zobeida; El Ouaamari, Abdelfattah; Gaulton, Kyle J.; Geisz, Andrea; Goodarzi, Mark O.; Hara, Manami; Hull-Meichle, Rebecca L.; Kleger, Alexander; Klein, Alison P.; Kopp, Janel L.; Kulkarni, Rohit N.; Muzumdar, Mandar D.; Naren, Anjaparavanda P.; Oakes, Scott A.; Olesen, Søren S.; Phelps, Edward A.; Powers, Alvin C.; Stabler, Cherie L.; Tirkes, Temel; Whitcomb, David C.; Yadav, Dhiraj; Yong, Jing; Zaghloul, Norann A.; Sander, Maike; Pandol, Stephen J.; Biology, School of Science
    The Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases Workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report summarizes the workshop proceedings. The goal of the workshop was to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into six major themes, including: (a) Pancreas Anatomy and Physiology; (b) Diabetes in the Setting of Exocrine Disease; (c) Metabolic Influences on the Exocrine Pancreas; (d) Genetic Drivers of Pancreatic Diseases; (e) Tools for Integrated Pancreatic Analysis; and (f) Implications of Exocrine-Endocrine Crosstalk. For each theme, there were multiple presentations followed by panel discussions on specific topics relevant to each area of research; these are summarized herein. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of the normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.
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    A multimodality test to guide the management of patients with a pancreatic cyst
    (American Association for the Advancement of Science, 2019-07-17) Springer, Simeon; Masica, David L.; Dal Molin, Marco; Douville, Christopher; Thoburn, Christopher J.; Afsari, Bahman; Li, Lu; Cohen, Joshua D.; Thompson, Elizabeth; Allen, Peter J.; Klimstra, David S.; Schattner, Mark A.; Schmidt, C. Max; Yip-Schneider, Michele; Simpson, Rachel E.; Castillo, Carlos Fernandez-Del; Mino-Kenudson, Mari; Brugge, William; Brand, Randall E.; Singhi, Aatur D.; Scarpa, Aldo; Lawlor, Rita; Salvia, Roberto; Zamboni, Giuseppe; Hong, Seung-Mo; Hwang, Dae Wook; Jang, Jin-Young; Kwon, Wooil; Swan, Niall; Geoghegan, Justin; Falconi, Massimo; Crippa, Stefano; Doglioni, Claudio; Paulino, Jorge; Schulick, Richard D.; Edil, Barish H.; Park, Walter; Yachida, Shinichi; Hijioka, Susumu; van Hooft, Jeanin; He, Jin; Weiss, Matthew J.; Burkhart, Richard; Makary, Martin; Canto, Marcia I.; Goggins, Michael G.; Ptak, Janine; Dobbyn, Lisa; Schaefer, Joy; Sillman, Natalie; Popoli, Maria; Klein, Alison P.; Tomasetti, Cristian; Karchin, Rachel; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Wolfgang, Christopher L.; Hruban, Ralph H.; Lennon, Anne Marie; Surgery, School of Medicine
    Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.