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      Management of Patients With Pancreatic Cancer Using the “Right Track” Model

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          Abstract

          Pancreatic cancer is one of the few cancer types in the US with incidence and death rates continuing to rise. As the disease threatens to become the second leading cause of cancer-related deaths in the country, it is imperative to review the best practices currently available to extend and improve patient lives. To provide a roadmap for healthcare professionals detecting, diagnosing, and caring for patients with pancreatic cancer as a supplement to national guidelines focused on recommended treatment regimens, the Pancreatic Cancer Action Network (PanCAN)’s Scientific and Medical Affairs staff and expert Scientific and Medical Advisory Board have created a series of position statements. The statements are based upon scientific evidence and clinical observations published in the literature and research conducted through PanCAN’s internal programs and initiatives. This review summarizes the rationale and sources for these position statements related to diagnosis, treatment, and care for pancreatic cancer and provides information about resources to make these recommendations accessible to patients and their medical teams. Pancreatic cancer is a complex and extremely challenging disease. Beyond treatment recommendations outlined in national guidelines, steps can be taken to help patients feel better and live longer. Under the framework of the “Right Track” model—right team, right tests, right treatments, data sharing—PanCAN’s position statements can provide supplementary guidance to healthcare professionals for the short- and long-term management of patients with the disease.

          Abstract

          The Pancreatic Cancer Action Network (PanCAN) position statements can provide supplementary guidance to healthcare professionals for the management of pancreatic cancer. This review summarizes the rationale and sources for these position statements related to diagnosis, treatment, and care and provides information about resources to make these recommendations accessible for patients and their medical teams.

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          Most cited references77

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          Cancer statistics, 2023

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.
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            Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

            The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.
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              Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

              (2017)
              We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.
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                Author and article information

                Contributors
                Journal
                Oncologist
                Oncologist
                oncolo
                The Oncologist
                Oxford University Press (US )
                1083-7159
                1549-490X
                July 2023
                12 April 2023
                12 April 2023
                : 28
                : 7
                : 584-595
                Affiliations
                Scientific and Medical Affairs, Pancreatic Cancer Action Network , Los Angeles, CA, USA
                Department of Hematology/Oncology, Vanderbilt-Ingram Cancer Center , Nashville, TN, USA
                Department of Gastroenterology Hepatology and Nutrition, MD Anderson Cancer Center , Houston, TX, USA
                Department of Gastrointestinal Oncology, University of Chicago , Chicago, IL, USA
                Scientific and Medical Affairs, Pancreatic Cancer Action Network , Los Angeles, CA, USA
                Scientific and Medical Affairs, Pancreatic Cancer Action Network , Los Angeles, CA, USA
                Oncology Nutrition Services, Dartmouth-Hitchcock Medical Center and Clinics , Lebanon, NH, USA
                Department of Surgery-General Surgery, Cedars-Sinai Medical Center , Los Angeles, CA, USA
                Department of Hematology & Medical Oncology, Virginia Mason Medical Center , Seattle, WA, USA
                Scientific and Medical Affairs, Pancreatic Cancer Action Network , Los Angeles, CA, USA
                Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute , Tampa, FL, USA
                Author notes
                Corresponding author: Allison Rosenzweig, PhD, Scientific & Medical Affairs, Pancreatic Cancer Action Network, 1500 Rosecrans Ave., Suite 200, Manhattan Beach, CA 90266, USA. Tel: 310-706-3383; Fax: 310-725-0029; Email: arosenzweig@ 123456pancan.org
                Corresponding author: Jason Fleming, MD, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. Email: jason.fleming@ 123456moffitt.org
                Author information
                https://orcid.org/0000-0003-1987-2725
                https://orcid.org/0000-0002-5450-842X
                Article
                oyad080
                10.1093/oncolo/oyad080
                10322133
                37043728
                2de2a4a8-0020-4d0d-87f8-373ff094bca7
                © The Author(s) 2023. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

                History
                : 26 January 2022
                : 17 February 2023
                Page count
                Pages: 12
                Categories
                Gastrointestinal Cancer
                AcademicSubjects/MED00010

                Oncology & Radiotherapy
                pancreatic cancer,guidelines,pancan,position statement,right track model
                Oncology & Radiotherapy
                pancreatic cancer, guidelines, pancan, position statement, right track model

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