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Pancreatic Neoplasms: HELP
Articles by Dr. E O'Reilly
Based on 101 articles published since 2008
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Between 2008 and 2019, E. O'Reilly wrote the following 101 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Guideline Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. 2018

Ter Veer, Emil / van Rijssen, L Bengt / Besselink, Marc G / Mali, Rosa M A / Berlin, Jordan D / Boeck, Stefan / Bonnetain, Franck / Chau, Ian / Conroy, Thierry / Van Cutsem, Eric / Deplanque, Gael / Friess, Helmut / Glimelius, Bengt / Goldstein, David / Herrmann, Richard / Labianca, Roberto / Van Laethem, Jean-Luc / Macarulla, Teresa / van der Meer, Jonathan H M / Neoptolemos, John P / Okusaka, Takuji / O'Reilly, Eileen M / Pelzer, Uwe / Philip, Philip A / van der Poel, Marcel J / Reni, Michele / Scheithauer, Werner / Siveke, Jens T / Verslype, Chris / Busch, Olivier R / Wilmink, Johanna W / van Oijen, Martijn G H / van Laarhoven, Hanneke W M. ·Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France. · Royal Marsden NHS Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Gastroenterology and Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. · Department of Oncology, Hôpital Riviera-Chablais, Vevey, Switzerland. · Department of Surgery, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Nelune Cancer Centre, Prince of Wales Hospital, Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia. · Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. · Cancer Center, ASST Papa Giovanni XXIII, Bergamo, Italy. · Department of Gastroenterology, Gastrointestinal Cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. · Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. · Department of Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine I, Medical University Vienna, Vienna, Austria. · Division of Solid Tumor Translational Oncology, West German Cancer Cancer, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. Electronic address: h.vanlaarhoven@amc.uva.nl. ·Lancet Oncol · Pubmed #29508762.

ABSTRACT: Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.

2 Guideline Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. 2017

Tempero, Margaret A / Malafa, Mokenge P / Al-Hawary, Mahmoud / Asbun, Horacio / Bain, Andrew / Behrman, Stephen W / Benson, Al B / Binder, Ellen / Cardin, Dana B / Cha, Charles / Chiorean, E Gabriela / Chung, Vincent / Czito, Brian / Dillhoff, Mary / Dotan, Efrat / Ferrone, Cristina R / Hardacre, Jeffrey / Hawkins, William G / Herman, Joseph / Ko, Andrew H / Komanduri, Srinadh / Koong, Albert / LoConte, Noelle / Lowy, Andrew M / Moravek, Cassadie / Nakakura, Eric K / O'Reilly, Eileen M / Obando, Jorge / Reddy, Sushanth / Scaife, Courtney / Thayer, Sarah / Weekes, Colin D / Wolff, Robert A / Wolpin, Brian M / Burns, Jennifer / Darlow, Susan. · ·J Natl Compr Canc Netw · Pubmed #28784865.

ABSTRACT: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

3 Guideline Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. 2016

Sohal, Davendra P S / Mangu, Pamela B / Khorana, Alok A / Shah, Manish A / Philip, Philip A / O'Reilly, Eileen M / Uronis, Hope E / Ramanathan, Ramesh K / Crane, Christopher H / Engebretson, Anitra / Ruggiero, Joseph T / Copur, Mehmet S / Lau, Michelle / Urba, Susan / Laheru, Daniel. ·Davendra P.S. Sohal and Alok A. Khorana, Cleveland Clinic, Cleveland, OH · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Manish A. Shah, The Weill Cornell Medical Center · Philip A. Philip, Karmanos Cancer Institute, Detroit · Susan Urba, University of Michigan Cancer Center, Ann Arbor, MI · Eileen M. O'Reilly, Memorial Sloan Kettering Cancer Center · Joseph T. Ruggiero, Weill Cornell Medical College, New York, NY · Hope E. Uronis, Duke University, Durham, NC · Ramesh K. Ramanathan, Mayo Clinic, Scottsdale · Michelle Lau, Community Hospital Based Cancer Center, Tempe, AZ · Christopher H. Crane, The University of Texas MD Anderson Cancer Center, Houston, TX · Anitra Engebretson, Patient Representative, Portland, OR · Mehmet S. Copur, St Francis Medical Center, Grand Island, NE · and Daniel Laheru, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD. ·J Clin Oncol · Pubmed #27247222.

ABSTRACT: PURPOSE: To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer. METHODS: American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Twenty-four randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens. Additional information is available at www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

4 Editorial Evolving panorama of treatment for metastatic pancreas adenocarcinoma. 2013

O'Reilly, Eileen M. · ·J Clin Oncol · Pubmed #23547071.

ABSTRACT: -- No abstract --

5 Editorial Targeting thrombosis in exocrine pancreas cancer: a continued need for improved therapies. 2011

Epstein, Andrew S / O'Reilly, Eileen M. · ·Expert Rev Anticancer Ther · Pubmed #22117145.

ABSTRACT: -- No abstract --

6 Editorial Refinement of adjuvant therapy for pancreatic cancer. 2010

O'Reilly, Eileen M. · ·JAMA · Pubmed #20823441.

ABSTRACT: -- No abstract --

7 Review Genomic profiling in pancreatic ductal adenocarcinoma and a pathway towards therapy individualization: A scoping review. 2019

Singh, Ritu R / Goldberg, Johanna / Varghese, Anna M / Yu, Kenneth H / Park, Wungki / O'Reilly, Eileen M. ·Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai St. Luke's and Mount Sinai West, New York, NY 10019, USA. Electronic address: ritu.singh@mountsinai.org. · MSK Library, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: goldbejb@mskcc.org. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA; David M. Rubenstein Center for Pancreatic Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA; David M. Rubenstein Center for Pancreatic Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: oreillye@mskcc.org. ·Cancer Treat Rev · Pubmed #30927677.

ABSTRACT: CONTEXT: Pancreatic cancer (PDAC) is one of the most challenging cancers to treat with modest recent improvements in survival from new systemic therapies. There is growing interest in individualized therapy underpinned by somatic and germline genomic alterations. OBJECTIVE: A systematic review of data on therapies targeting somatic and germline alterations, and their downstream pathways in PDAC. METHOD: A systematic literature search was conducted using PRISMA guidelines to include relevant results published after January 1, 2008. RESULTS: A total of 71 relevant studies were included. We identified 36 studies targeting the KRAS-pathway, the most common being with MEK-inhibitor therapy. Twenty-two studies were identified that evaluated platinum-based chemotherapy and PARP inhibitors in patients with deleterious mutations in DNA damage repair genes and have shown encouraging results. Immunotherapy has demonstrated activity in patients with mismatch repair deficiency/microsatellite instability. CONCLUSION: Evidence from translational and clinical research presents an exciting platform for genomic targeted therapy in PDAC. Validity for targeting BRCA with platinum and PARP inhibitors and microsatellite instability with immune therapy has been established, nonetheless, evidence for targeting the common driver oncogenes is lacking and much work is needed. Of importance is identifying the subgroup of KRAS -wild type PDAC (approximately 5%) where there is enrichment for targetable opportunities.

8 Review Ablative Radiotherapy Doses for Locally Advanced: Pancreatic Cancer (LAPC). 2017

Crane, Christopher H / O'Reilly, Eileen M. · ·Cancer J · Pubmed #29189331.

ABSTRACT: Standard palliative doses of radiation for locally advanced unresectable pancreatic cancer have had minimal to no impact on survival. Randomized trials evaluating these palliative doses have not shown a significant survival benefit with the use of radiation as consolidation after chemotherapy. Results from nonrandomized studies of 3- to 5-fraction low-dose stereotactic radiation (SBRT) have likewise had a minimal impact, but with less toxicity and a shorter treatment time. Doses of SBRT have been reduced to half the level that is necessary (biological equivalent dose, BED of 53 Gy) to achieve tumor ablation in the treatment of other solid tumors (100 Gy BED) to protect the gastrointestinal (GI) tract. The survival benefit of these palliative options is modest. In contrast, ablative doses of radiation (100 Gy BED) can be delivered using the same SBRT technique in 15 to 25 fractions. In addition to precision tumor targeting and solutions for respiratory motion as with SBRT, the delivery of ablative doses takes advantage of heterogeneous dosing, increased fractionation, which allows higher doses to be given, as well as adaptive planning to address day-to-day GI tract motion in selected cases. These higher doses have resulted in encouraging long-term survival results in multiple studies. In this review, we discuss the critical concepts and components of techniques that can be used to deliver ablative radiotherapy doses for patients with pancreatic tumors: fractionation, intentional dose heterogeneity, respiratory gating, image guidance, and adaptive planning.

9 Review Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients. 2017

Dhir, Mashaal / Malhotra, Gautam K / Sohal, Davendra P S / Hein, Nicholas A / Smith, Lynette M / O'Reilly, Eileen M / Bahary, Nathan / Are, Chandrakanth. ·Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA. · Department of Surgery, University of Nebraska Medical Center, Omaha, NE, 98198, USA. · Division of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. · Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, 68198, USA. · David M. Rubenstein Center for Pancreatic Cancer, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, 15232, USA. · Department of Surgery, Division of Surgical Oncology, University of Nebraska Medical Center, Omaha, NE, 98198, USA. care@unmc.edu. · Department of Surgery/Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA. care@unmc.edu. ·World J Surg Oncol · Pubmed #29017581.

ABSTRACT: BACKGROUND: Recent years have seen standardization of the anatomic definitions of pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy (NAT). The aim of the current review was to summarize the evidence for NAT in pancreatic adenocarcinoma since 2009, when consensus criteria for resectable (R), borderline resectable (BR), and locally advanced (LA) disease were endorsed. METHODS: PubMed search was undertaken along with extensive backward search of the references of published articles to identify studies utilizing NAT for pancreatic adenocarcinoma. Abstracts from ASCO-GI 2014 and 2015 were also searched. RESULTS: A total of 96 studies including 5520 patients were included in the final quantitative synthesis. Pooled estimates revealed 36% grade ≥ 3 toxicities, 5% biliary complications, 21% hospitalization rate and low mortality (0%, range 0-16%) during NAT. The majority of patients (59%) had stable disease. On an intention-to-treat basis, R0-resection rates varied from 63% among R patients to 23% among LA patients. R0 rates were > 80% among all patients who were resected after NAT. Among R and BR patients who underwent resection after NAT, median OS was 30 and 27.4 months, respectively. CONCLUSIONS: The current study summarizes the recent literature for NAT in pancreatic adenocarcinoma and demonstrates improving outcomes after NAT compared to those historically associated with a surgery-first approach for pancreatic adenocarcinoma.

10 Review Immunotherapy in pancreatic ductal adenocarcinoma: an emerging entity? 2017

Sahin, I H / Askan, G / Hu, Z I / O'Reilly, E M. ·Department of Medicine, Emory University School of Medicine, Atlanta. · Department of Pathology, Pathology, Memorial Sloan Kettering Cancer Center, New York. · Department of Medicine, Icahn School of Medicine, Mount Sinai Health System, New York. · Department of Medicine, Weill Cornell Medicine, New York, USA. ·Ann Oncol · Pubmed #28945842.

ABSTRACT: The genomic-plasticity of the immune system creates a broad immune repertoire engaged to tackle cancer cells. Promising clinical activity has been observed with several immune therapy strategies in solid tumors including melanoma, lung, kidney, and bladder cancers, albeit as yet immunotherapy-based treatment approaches in pancreatic ductal adenocarcinoma (PDAC) remain to have proven value. While translational and early clinical studies have demonstrated activation of antitumor immunity, most recent late-phase clinical trials have not confirmed the early promise in PDAC except in MSI-High PDAC patients. These results may in part be explained by multiple factors, including the poorly immunogenic nature of PDAC along with immune privilege, the complex tumor microenvironment, and the genetic plasticity of PDAC cells. These challenges have led to disappointments in the field, nonetheless they have also advanced our understanding that may tailor the future steps for immunotherapy for PDAC. Therefore, there is significant hope that progress is on the horizon.

11 Review Pancreatic ductal adenocarcinoma: State-of-the-art 2017 and new therapeutic strategies. 2017

Chiaravalli, Marta / Reni, Michele / O'Reilly, Eileen M. ·Medical Oncology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States. · Medical Oncology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy. · Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Weill Cornell Medical College, Weill Cornell Medicine, New York, NY 10065, United States. Electronic address: oreillye@mskcc.org. ·Cancer Treat Rev · Pubmed #28869888.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an overall 5-year survival of 8% for all stages combined. The majority of patients present with stage IV disease at diagnosis and these patients have an overall 5-year survival of 3%. Currently, the standard of care for metastatic pancreas adenocarcinoma is combination cytotoxic therapy, namely FOLFIRINOX or gemcitabine plus nab-paclitaxel for good performance status patients. Given the challenges and the rising incidence of PDAC expected to become the second leading cause of cancer-related death by 2030, there is a major unmet need to develop more effective therapies. In this setting, the molecular and genomic characterization of PDAC have underpinned the use of targeted therapies. To date, the results from targeted agent evaluation have been disappointing with some exceptions. Novel promising strategies depend on biomarker identification and patient selection e.g. germline mutations in DNA repair or mismatch repair genes, where the addition of a platinum agent or checkpoint inhibitor can have a positive impact on survival. This article will review the state-of-the-art treatment of metastatic pancreatic cancer with an emphasis on novel promising therapeutic strategies and an overview on emerging biomarkers.

12 Review Management of Metastatic Pancreatic Adenocarcinoma. 2016

Cheema, Ahmad R / O'Reilly, Eileen M. ·Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Pl, New York, NY 10029, USA; Department of Medicine, Mount Sinai St. Luke's-West Hospital Center, 1111 Amsterdam Avenue, New York, NY 10025, USA. · Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, Office 1021, New York, NY 10065, USA; Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: oreillye@mskcc.org. ·Surg Clin North Am · Pubmed #27865284.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and clinically challenging malignancies to treat, with an estimated 5-year survival rate of approximately 7%. At the time of initial presentation, a majority of patients have metastatic disease. The median overall survival in these patients with good performance status is 8.5 to 11.1 months and in patients with significantly impaired performance status, even less. Strategies to integrate novel agents with traditional cytotoxic therapies are under investigation and hold promise for improving outcomes in patients with metastatic PDAC. This article focuses on the current management options and novel therapeutics for metastatic PDAC.

13 Review Current management and future directions in metastatic pancreatic adenocarcinoma. 2016

Varghese, Anna M / Lowery, Maeve A / Yu, Kenneth H / O'Reilly, Eileen M. ·Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. ·Cancer · Pubmed #27649047.

ABSTRACT: Of the anticipated 50,000 individuals expected to be diagnosed with pancreatic cancer in 2016, the majority will have metastatic disease. Given the noncurative nature of advanced pancreatic adenocarcinoma, treatment is aimed at inducing disease regression, controlling symptom, and extending life. The last 5 years have been marked by advances in the treatment of metastatic pancreatic cancer, specifically the approval by the US Food and Drug Administration of 2 combination chemotherapy regimens and the widespread use of a third, which have reproducibly been shown to improve survival. Ongoing studies are building on these regimens along with targeted and immunotherapeutic agents. This article will review the current treatment standards and emerging targets for metastatic pancreatic cancer. Cancer 2016;122:3765-3775. © 2016 American Cancer Society.

14 Review Adjuvant and Neoadjuvant Therapy for Pancreatic Cancer. 2016

Li, Daneng / O'Reilly, Eileen M. ·Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. · Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: oreillye@mskcc.org. ·Surg Oncol Clin N Am · Pubmed #27013366.

ABSTRACT: Pancreas adenocarcinoma is an aggressive malignancy. The risk of recurrence remains high even for patients with localized disease undergoing surgical resection. Adjuvant systemic therapy has demonstrated the ability to reduce the risk of recurrence and prolong survival. Determination of optimal adjuvant treatment, systemic therapy, and/or combinations to further improve recurrence rates and overall survival are still needed. Neoadjuvant therapy represents an alternative emerging paradigm of investigation with several theoretic advantages over adjuvant therapy. This article summarizes the major adjuvant and neoadjuvant studies for pancreas adenocarcinoma and highlights key areas of ongoing investigation.

15 Review Genomic instability in pancreatic adenocarcinoma: a new step towards precision medicine and novel therapeutic approaches. 2016

Sahin, Ibrahim H / Lowery, Maeve A / Stadler, Zsofia K / Salo-Mullen, Erin / Iacobuzio-Donahue, Christine A / Kelsen, David P / O'Reilly, Eileen M. ·a Department of Medicine , Icahn School of Medicine at Mount Sinai St Luke's Roosevelt Hospital Center , New York , NY , USA. · b Department of Medicine , Memorial Sloan Kettering Cancer Center , New York , NY , USA. · c Department of Medicine , Weill Cornell Medical College , New York , NY , USA. ·Expert Rev Gastroenterol Hepatol · Pubmed #26881472.

ABSTRACT: Pancreatic cancer is one of the most challenging cancers. Whole genome sequencing studies have been conducted to elucidate the underlying fundamentals underscoring disease behavior. Studies have identified a subgroup of pancreatic cancer patients with distinct molecular and clinical features. Genetic fingerprinting of these tumors is consistent with an unstable genome and defective DNA repair pathways, which creates unique susceptibility to agents inducing DNA damage. BRCA1/2 mutations, both germline and somatic, which lead to impaired DNA repair, are found to be important biomarkers of genomic instability as well as of response to DNA damaging agents. Recent studies have elucidated that PARP inhibitors and platinum agents may be effective to induce tumor regression in solid tumors bearing an unstable genome including pancreatic cancer. In this review we discuss the characteristics of genomic instability in pancreatic cancer along with its clinical implications and the utility of DNA targeting agents particularly PARP inhibitors as a novel treatment approach.

16 Review Molecular signature of pancreatic adenocarcinoma: an insight from genotype to phenotype and challenges for targeted therapy. 2016

Sahin, Ibrahim H / Iacobuzio-Donahue, Christine A / O'Reilly, Eileen M. ·a 1 Icahn School of Medicine at Mount Sinai St Luke's Roosevelt Hospital Center , NY, USA. · b 2 Memorial Sloan Kettering Cancer Center , NY, USA. · c 3 Weill Medical College of Cornell University, David M. Rubenstein Center for Pancreatic Cancer Research , 300 East 66th street, office 1021, NY 10065, USA ; oreillye@mskcc.org. ·Expert Opin Ther Targets · Pubmed #26439702.

ABSTRACT: INTRODUCTION: Pancreatic adenocarcinoma remains one of the most clinically challenging cancers despite an in-depth characterization of the molecular underpinnings and biology of this disease. Recent whole-genome-wide studies have elucidated the diverse and complex genetic alterations which generate a unique oncogenic signature for an individual pancreatic cancer patient and which may explain diverse disease behavior in a clinical setting. AREAS COVERED: In this review article, we discuss the key oncogenic pathways of pancreatic cancer including RAS-MAPK, PI3KCA and TGF-β signaling, as well as the impact of these pathways on the disease behavior and their potential targetability. The role of tumor suppressors particularly BRCA1 and BRCA2 genes and their role in pancreatic cancer treatment are elaborated upon. We further review recent genomic studies and their impact on future pancreatic cancer treatment. EXPERT OPINION: Targeted therapies inhibiting pro-survival pathways have limited impact on pancreatic cancer outcomes. Activation of pro-apoptotic pathways along with suppression of cancer-stem-related pathways may reverse treatment resistance in pancreatic cancer. While targeted therapy or a 'precision medicine' approach in pancreatic adenocarcinoma remains an elusive challenge for the majority of patients, there is a real sense of optimism that the strides made in understanding the molecular underpinnings of this disease will translate into improved outcomes.

17 Review Genetic Diversity of Pancreatic Ductal Adenocarcinoma and Opportunities for Precision Medicine. 2016

Knudsen, Erik S / O'Reilly, Eileen M / Brody, Jonathan R / Witkiewicz, Agnieszka K. ·Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: erik.knudsen@utsouthwestern.edu. · Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Surgery, Jefferson Pancreatic, Biliary, and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. · Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: agnes.witkiewicz@utsouthwestern.edu. ·Gastroenterology · Pubmed #26385075.

ABSTRACT: Patients with pancreatic ductal adenocarcinoma (PDA) have a poor prognosis despite new treatments; approximately 7% survive for 5 years. Although there have been advances in systemic, primarily cytotoxic, therapies, it has been a challenge to treat patients with PDA using targeted therapies. Sequence analyses have provided a wealth of information about the genetic features of PDA and have identified potential therapeutic targets. Preclinical and early-phase clinical studies have found specific pathways could be rationally targeted; it might also be possible to take advantage of the genetic diversity of PDAs to develop therapeutic agents. The genetic diversity and instability of PDA cells have long been thought of as obstacles to treatment, but are now considered exploitable features. We review the latest findings in pancreatic cancer genetics and the promise of targeted approaches in PDA therapy.

18 Review Novel Therapeutics for Pancreatic Adenocarcinoma. 2015

Lowery, Maeve A / O'Reilly, Eileen M. ·Gastrointestinal Oncology Service, Department of Medicine, Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, 300 East 66th Street, New York, NY 10065, USA. · Gastrointestinal Oncology Service, Department of Medicine, Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, 300 East 66th Street, New York, NY 10065, USA. Electronic address: oreillye@mskcc.org. ·Hematol Oncol Clin North Am · Pubmed #26226910.

ABSTRACT: The last decade has seen significant developments in the use of combination systemic therapy for advanced pancreatic ductal adenocarcinoma (PDAC), with median survival approaching 1 year for select patients treated with FOLFIRINOX in the metastatic setting. However, it is sobering that these developments have been achieved with the use of traditional cytotoxics rather than from successes in the more modern fields of molecularly targeted therapies or immunotherapy. This article highlights several promising therapeutic approaches to PDAC currently under clinical evaluation, including immune therapies, molecularly targeted therapies, strategies for stromal depletion, and targeted therapy for genetically selected patients.

19 Review Adjuvant and neoadjuvant systemic therapy for pancreas adenocarcinoma. 2015

Li, Daneng / O'Reilly, Eileen M. ·Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY. · Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: oreillye@mskcc.org. ·Semin Oncol · Pubmed #25726058.

ABSTRACT: The last two decades of research in the adjuvant setting of pancreas adenocarcinoma have established the value of adjuvant systemic therapy as being able to delay recurrence and increase overall survival. International standards of care in the adjuvant setting include either 6 months of gemcitabine or 5-fluorouracil and leucovorin. The added value of additional agents in the adjuvant setting is being evaluated in several large adjuvant studies. The role of a targeted agent in the adjuvant setting remains investigational. Other major areas of exploration include the integration of adjuvant immunotherapeutic approaches, which provide promise in a setting of micrometastatic disease volumes where such approaches may have greatest value.

20 Review Novel directions in neoadjuvant therapy for pancreas adenocarcinoma. 2015

Yang, Andrew / O'Reilly, Eileen M. ·Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 East 66th street, Office 1021, New York, NY 10065, USA. ·Expert Rev Gastroenterol Hepatol · Pubmed #25686370.

ABSTRACT: Surgical resection of pancreatic carcinoma has long represented the only viable option for a potential cure of pancreas cancer. The use of adjuvant chemotherapy post-resection has been established in treating micro metastases and prolonging disease-free survival. However, studies of neoadjuvant therapy have not come to any definitive conclusion regarding the overall efficacy of such treatment, despite the theoretical benefits. In this review, we examine the historical precedent as well as the current state of affairs regarding neoadjuvant therapy in resectable and borderline resectable pancreatic adenocarcinoma. In addition, we review the definitions for resectable and borderline resectable disease and highlight key areas of clinical investigation in the field and summarize the major ongoing neoadjuvant studies focused on resectable pancreatic adenocarcinoma.

21 Review Sunitinib malate for the treatment of pancreas malignancies--where does it fit? 2013

Mankal, Pavan / O'Reilly, Eileen. ·Columbia University College of Physicians and Surgeons, St. Luke's-Roosevelt Hospital Center, Department of Medicine, New York, USA. ·Expert Opin Pharmacother · Pubmed #23458511.

ABSTRACT: INTRODUCTION: Sunitinib , a broad-spectrum multikinase inhibitor, was recently approved for use in progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs). Its mechanism of action affects various signaling cascades involving antiangiogenesis and tumor proliferation, including vascular endothelial growth factors and platelet-derived growth factors. AREAS COVERED: In this article, we review sunitinib's mechanism of action at a molecular level and review key preclinical and clinical studies for pNETs and more limited data regarding sunitinib's evaluation in pancreas adenocarcinoma. The data for sunitinib in pNETs are placed in the context of the changing landscape of therapeutic options for this cancer, and relevant ongoing clinical trials and future directions are highlighted. EXPERT OPINION: Sunitinib malate has become integrated into routine clinical management for pNETs; however, its role in pancreas adenocarcinoma is not established.

22 Review Adjuvant therapy for pancreas adenocarcinoma. 2013

O'Reilly, Eileen M. ·Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. oreillye@mskcc.org ·J Surg Oncol · Pubmed #22886586.

ABSTRACT: Adjuvant therapy for pancreas adenocarcinoma in 2012 includes consideration of systemic therapy based on high level evidence and combined chemoradiotherapy based on less robust data. Current major adjuvant questions are examining the role of the addition of a second agent, either cytotoxic or targeted agent, to gemcitabine and whether or not the utilization of combined chemoradiotherapy improves overall survival. Progress to date has been modest and incremental in the adjuvant setting.

23 Review Postresection surveillance for pancreatic cancer performance status, imaging, and serum markers. 2012

O'Reilly, Eileen M / Lowery, Maeve A. ·Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. oreillye@mskcc.org ·Cancer J · Pubmed #23187849.

ABSTRACT: Approximately 15% of patients with a diagnosis of pancreatic adenocarcinoma are candidates for potentially curative surgery. However, most patients who undergo such surgery will die from recurrent disease, most within the first few years, whereas nearly all succumb by 5 to 7 years from diagnosis. Currently, there is a lack of high-level evidence to guide consensus recommendations as to the optimal surveillance strategy after resection. There is considerable variability in clinical practice, ranging from frequent clinical follow-up, with serial Ca 19-9 measurement and routine computed tomographic imaging on a 3- to 6-monthly basis, to a practice of no routine serum or imaging follow-up after surgery. In most part, this divergence in practice reflects a lack of data to define optimal practice. The argument in favor of limited surveillance presumably stems from the relatively uniform poor outcomes after recurrence and the absence of evidence indicating that early detection of local, regional, or metastatic recurrence improves outcomes. However, recent advancements in the treatment of metastatic disease offer hope that earlier detection and initiation of treatment for recurrent disease may positively impact clinical outcomes and at least urges review of the topic. One advantage to the development of defined guidelines would be greater consistency in the setting of both routine clinical follow-up and follow-up after adjuvant therapy on trial.

24 Review Exocrine pancreas cancer and thromboembolic events: a systematic literature review. 2012

Epstein, Andrew S / O'Reilly, Eileen M. ·Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ·J Natl Compr Canc Netw · Pubmed #22773799.

ABSTRACT: Exocrine pancreas cancer continues to represent a significant therapeutic challenge, with high rates of mortality and morbidity, including from thromboembolic events, which have long been described as a frequent complication of the disease. This article provides a systematic and comprehensive review of the literature to address the clinical and pathologic features recognized in pancreas cancer pertaining to thrombosis, and to discuss ongoing investigations of prophylactic anticoagulation in the hopes of improving disease-related outcomes.

25 Review Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature. 2012

Karamurzin, Yevgeniy / Zeng, Zhaoshi / Stadler, Zsofia K / Zhang, Liying / Ouansafi, Ihsane / Al-Ahmadie, Hikmat A / Sempoux, Christine / Saltz, Leonard B / Soslow, Robert A / O'Reilly, Eileen M / Paty, Philip B / Coit, Daniel G / Shia, Jinru / Klimstra, David S. ·Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ·Hum Pathol · Pubmed #22516243.

ABSTRACT: Immunohistochemical detection of DNA mismatch repair proteins and polymerase chain reaction detection of microsatellite instability have enhanced the recognition of mismatch repair-deficient neoplasms in patients with Lynch syndrome and, consequently, led to the identification of tumors that have not been included in the currently known Lynch syndrome tumor spectrum. Here, we report 4 such unusual tumors. Three of the 4, a peritoneal mesothelioma, a pancreatic acinar cell carcinoma, and a pancreatic well-differentiated neuroendocrine tumor, represented tumor types that, to the best of our knowledge, have not been previously reported in Lynch syndrome. The fourth tumor was an adrenocortical carcinoma, which has rarely been reported previously in Lynch syndrome. Three of our 4 patients carried a pathogenic germ-line mutation in a mismatch repair gene. The unusual tumor in each of the 3 patients showed loss of the mismatch repair protein corresponding to the mutation. The fourth patient did not have mutation information but had a history of colonic and endometrial carcinomas; both lacked MSH2 and MSH6 proteins. Interestingly, none of the 4 unusual tumors revealed microsatellite instability on polymerase chain reaction testing, whereas an appendiceal carcinoma from 1 of the study patients who was tested simultaneously did. The recognition of such tumors expands the repertoire of usable test samples for the workup of high-risk families. As yet, however, there are no data to support the inclusion of these tumors into general screening guidelines for detecting Lynch syndrome, nor are there data to warrant surveillance for these tumors in patients with Lynch syndrome.

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