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Pancreatic Neoplasms: HELP
Articles by Dr. M Tempero
Based on 35 articles published since 2009
(Why 35 articles?)
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Between 2009 and 2019, M. Tempero wrote the following 35 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 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.

2 Guideline Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. 2012

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen W / Ben-Josef, Edgar / Benson, Al B / Casper, Ephraim S / Cohen, Steven J / Czito, Brian / Ellenhorn, Joshua D I / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Ma, Wen Wee / Malafa, Mokenge P / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Sasson, Aaron R / Tally, Anitra / Thayer, Sarah P / Whiting, Samuel / Wolff, Robert A / Wolpin, Brian M / Freedman-Cass, Deborah A / Shead, Dorothy A / Anonymous1061005. ·UCSF Helen Diller Family Comprehensive Cancer Center. ·J Natl Compr Canc Netw · Pubmed #22679115.

ABSTRACT: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.

3 Guideline Pancreatic adenocarcinoma. 2010

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen / Ben-Josef, Edgar / Benson, Al B / Berlin, Jordan D / Cameron, John L / Casper, Ephraim S / Cohen, Steven J / Duff, Michelle / Ellenhorn, Joshua D I / Hawkins, William G / Hoffman, John P / Kuvshinoff, Boris W / Malafa, Mokenge P / Muscarella, Peter / Nakakura, Eric K / Sasson, Aaron R / Thayer, Sarah P / Tyler, Douglas S / Warren, Robert S / Whiting, Samuel / Willett, Christopher / Wolff, Robert A / Anonymous3820673. · ·J Natl Compr Canc Netw · Pubmed #20876541.

ABSTRACT: -- No abstract --

4 Review Introduction: Pancreatic Adenocarcinoma: The Emperor of All Cancer Maladies. 2017

Tempero, Margaret A. ·From the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. ·Cancer J · Pubmed #29189324.

ABSTRACT: -- No abstract --

5 Review Pancreatic cancer. 2016

Kleeff, Jorg / Korc, Murray / Apte, Minoti / La Vecchia, Carlo / Johnson, Colin D / Biankin, Andrew V / Neale, Rachel E / Tempero, Margaret / Tuveson, David A / Hruban, Ralph H / Neoptolemos, John P. ·NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. · Department of General, Visceral and Pediatric Surgery, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany. · Departments of Medicine, and Biochemistry and Molecular Biology, Indiana University School of Medicine, the Melvin and Bren Simon Cancer Center, and the Pancreatic Cancer Signature Center, Indianapolis, Indiana, USA. · SWS Clinical School, University of New South Wales, and Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia. · Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. · University Surgical Unit, University Hospital Southampton, Southampton, UK. · Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, UK. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · UCSF Pancreas Center, University of California San Francisco - Mission Bay Campus/Mission Hall, San Francisco, California, USA. · Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York, USA. · The Sol Goldman Pancreatic Cancer Research Center, Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Nat Rev Dis Primers · Pubmed #27158978.

ABSTRACT: Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management.

6 Review Therapeutic advances in pancreatic cancer. 2013

Paulson, Andrew Scott / Tran Cao, Hop S / Tempero, Margaret A / Lowy, Andrew M. ·University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, USA. ·Gastroenterology · Pubmed #23622141.

ABSTRACT: Despite our improved understanding of pancreatic cancer biology and ability to perform more complex pancreatic cancer surgeries that produce better short-term outcomes, major progress toward increasing survival times has been painstakingly slow. Through the often-repeated, dismal survival statistics, it is easy to lose sight of real progress that has been made in pancreatic cancer therapy. It is particularly interesting to observe the extent to which these advances are interdependent and the effects they have had on practice. For example, during the past 5-10 years, we have seen widespread adoption of pancreatic imaging protocols that allow for objectively defined criteria of resectability. This has led to the definition of "borderline resectable pancreatic cancer"--a new clinical category that has affected the design of clinical trials. A major change in our surgical approach has been the move to minimally invasive pancreatectomy, which continues to gain broader acceptance and use, particularly for left-sided lesions. Although many new agents have been developed aimed at putative molecular targets, recent breakthroughs in therapy for advanced disease have arisen from our ability to safely give patients combination cytotoxic chemotherapy. We are now faced with the challenge of combining multidrug, cytotoxic chemotherapies with newer-generation agents. Ultimately, the hope is that drug combinations will be selected based on biomarkers, and strategies for pancreatic cancer therapy will be personalized, which could prolong patients' lives and reduce toxicity. We review the major advances in pancreatic cancer therapy during the last 5 years, and discuss how these have set the stage for greater progress in the near future.

7 Review Changing the way we do business: recommendations to accelerate biomarker development in pancreatic cancer. 2013

Tempero, Margaret A / Klimstra, David / Berlin, Jordan / Hollingsworth, Tony / Kim, Paula / Merchant, Nipun / Moore, Malcolm / Pleskow, Doug / Wang-Gillam, Andrea / Lowy, Andrew M. ·Pancreas Center, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94115, USA. mtempero@medicine.ucsf.edu ·Clin Cancer Res · Pubmed #23344262.

ABSTRACT: Pancreatic ductal adenocarcinoma is the most aggressive of all epithelial malignancies. In contrast to the favorable trends seen in most other common malignancies, the five-year survival of patients with this disease remains only 6%, a statistic that has changed minimally for decades. Only two drugs have been approved by the U.S. Food and Drug Administration (FDA) for use in pancreatic cancer in the last 15 years, and there are no established strategies for early detection.

8 Review Monoclonal antibodies and other targeted therapies for pancreatic cancer. 2012

Cinar, Pelin / Tempero, Margaret A. ·Department of Medicine, University of California, San Francisco, CA, USA. ·Cancer J · Pubmed #23187854.

ABSTRACT: Pancreatic cancer continues to be a challenging disease to treat because of its aggressive nature, advanced stage at the time of diagnosis, and limited treatment options that are available. Traditional cytotoxic chemotherapy provides modest benefit to patients with pancreatic adenocarcinoma. Recently, a FOLFIRINOX regimen revealed improved response in overall and progression-free survival over single-agent gemcitabine in metastatic pancreatic cancer, but there is still much needed advancement in the systemic treatment of pancreatic cancer. There is a growing interest in the development of novel agents, while our understanding of molecular pathogenesis of pancreatic adenocarcinoma continues to expand. With identification of various molecular pathways in pancreatic cancer tumorigenesis, potential targets for drug development have been pursued with the use of monoclonal antibodies and small-molecule inhibitors. Although preclinical studies with multiple targeted therapies demonstrated encouraging results in pancreatic cancer, only erlotinib, an epidermal growth factor receptor inhibitor, showed a marginal survival benefit in a phase III clinical trial, when combined with gemcitabine. As further signaling pathways and their importance in pancreatic cancer tumorigenesis are better understood, further clinical trials will need to be designed to study these targeted agents as single agents, in combination with other novel agents or in combination with cytotoxic chemotherapy. In this review, we present the current knowledge on targeted therapy in pancreatic adenocarcinoma and its application in clinical practice.

9 Review Pancreatic cancer treatment and research: an international expert panel discussion. 2011

Tempero, M A / Berlin, J / Ducreux, M / Haller, D / Harper, P / Khayat, D / Schmoll, H-J / Sobrero, A / Van Cutsem, E. ·Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, USA. mtempero@medicine.ucsf.edu ·Ann Oncol · Pubmed #21199884.

ABSTRACT: BACKGROUND: Pancreatic cancer has proven extremely challenging to treat. A collaborative effort is needed to advance research and improve treatment. An expert conference was conducted to elicit perspectives regarding the current treatment and future research of pancreatic cancer. METHODS: The conference comprised an international panel of experts representing five European countries and the United States. RESULTS: Adjuvant radiotherapy is used more frequently in the United States than in Europe. In locally advanced disease, there is now more emphasis on early chemotherapy in both Europe and the United States. In metastatic disease, combination chemotherapy is commonly used in Europe and the United States. This varies by country. Advancing pancreatic research will require improving biorepositories and developing a roadmap to prioritize therapeutic targets in different models. Small randomized phase II trials of both non-selected and enriched patient populations will help identify activity of new agents. Phase III trials should only be initiated in appropriate patients based on strong clinical and biological signals. Developing drugs in the adjuvant setting may be preferable to eliminate some of the challenges of drug development in the advanced disease setting. CONCLUSION: Progress in research combined with encouraging improvements from the past offer hope for the future of pancreatic cancer patients.

10 Review Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. 2009

Philip, Philip A / Mooney, Margaret / Jaffe, Deborah / Eckhardt, Gail / Moore, Malcolm / Meropol, Neal / Emens, Leisha / O'Reilly, Eileen / Korc, Murray / Ellis, Lee / Benedetti, Jacqueline / Rothenberg, Mace / Willett, Christopher / Tempero, Margaret / Lowy, Andrew / Abbruzzese, James / Simeone, Diane / Hingorani, Sunil / Berlin, Jordan / Tepper, Joel. ·Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA. philipp@karmanos.org ·J Clin Oncol · Pubmed #19858397.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality, despite significant improvements in diagnostic imaging and operative mortality rates. The 5-year survival rate remains less than 5% because of microscopic or gross metastatic disease at time of diagnosis. The Clinical Trials Planning Meeting in pancreatic cancer was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to discuss the integration of basic and clinical knowledge in the design of clinical trials in PDAC. Major emphasis was placed on the enhancement of research to identify and validate the relevant targets and molecular pathways in PDAC, cancer stem cells, and the microenvironment. Emphasis was also placed on developing rational combinations of targeted agents and the development of predictive biomarkers to assist selection of patient subsets. The development of preclinical tumor models that are better predictive of human PDAC must be supported with wider availability to the research community. Phase III clinical trials should be implemented only if there is a meaningful clinical signal of efficacy and safety in the phase II setting. The emphasis must therefore be on performing well-designed phase II studies with uniform sets of basic entry and evaluation criteria with survival as a primary endpoint. Patients with either metastatic or locally advanced PDAC must be studied separately.

11 Clinical Trial HALO-109-301: a Phase III trial of PEGPH20 (with gemcitabine and nab-paclitaxel) in hyaluronic acid-high stage IV pancreatic cancer. 2018

Doherty, Gary J / Tempero, Margaret / Corrie, Pippa G. ·Department of Oncology, University of Cambridge, Box 193, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK. · Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Box 193, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK. · Pancreas Center, University of California, San Francisco, CA 94158, USA. ·Future Oncol · Pubmed #29235360.

ABSTRACT: The outlook for patients with advanced pancreatic cancer remains poor, despite significant advances in our understanding of pancreatic tumor biology. One emerging theme highlights the distinct composition of the pancreatic tumor microenvironment. Hyaluronic acid is a hydrophilic glycosaminoglycan whose production within the tumor leads to increased interstitial tumor pressure, thereby limiting the access of potentially effective circulating anticancer drugs via reduced tumor perfusion. PEGylated rHuPH20 is a multiply PEGylated recombinant human hyaluronidase that has shown promising efficacy in preclinical models and early phase clinical trials in pancreatic cancer patients. Here, we discuss these findings, and the rationale for the ongoing randomized Phase III trial (HALO-109-301), which seeks to definitively define the efficacy of PEGylated rHuPH20 alongside gemcitabine and nab-paclitaxel in previously untreated, hyaluronic acid-high, stage IV pancreatic cancer.

12 Clinical Trial A Randomized, Double-Blinded, Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial. 2017

Ko, Andrew H / Murphy, Patrick B / Peyton, James D / Shipley, Dianna L / Al-Hazzouri, Ahmed / Rodriguez, Francisco A / Womack, Mark S / Xiong, Henry Q / Waterhouse, David M / Tempero, Margaret A / Guo, Shuangli / Lane, Cassie M / Earwood, Chris / DeBusk, Laura M / Bendell, Johanna C. ·Division of Hematology and Oncology, University of California, San Francisco, California, USA andrew.ko@ucsf.edu. · Tennessee Oncology, PLLC/SCRI, Nashville, Tennessee, USA. · Florida Cancer Specialists/SCRI, Fort Myers, Florida, USA. · Tennessee Oncology, PLLC/SCRI, Chattanooga, Tennessee, USA. · The Center for Cancer and Blood Disorders/SCRI, Fort Worth, Texas, USA. · Oncology Hematology Care/SCRI, Cincinnati, Ohio, USA. · Division of Hematology and Oncology, University of California, San Francisco, California, USA. · Sarah Cannon Research Institute (SCRI), Nashville, Tennessee, USA. ·Oncologist · Pubmed #28935773.

ABSTRACT: LESSONS LEARNED: The addition of the heat shock protein 27 (Hsp27)-targeting antisense oligonucleotide, apatorsen, to a standard first-line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation. BACKGROUND: This randomized, double-blinded, phase II trial evaluated the efficacy of gemcitabine/nab-paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer. METHODS: Patients were randomized 1:1 to Arm A (gemcitabine/nab-paclitaxel plus apatorsen) or Arm B (gemcitabine/nab-paclitaxel plus placebo). Treatment was administered in 28-day cycles, with restaging every 2 cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and on treatment. The primary endpoint was overall survival (OS). RESULTS: One hundred thirty-two patients were enrolled, 66 per arm. Cytopenias and fatigue were the most frequent grade 3/4 treatment-related adverse events for both arms. Median progression-free survival (PFS) and OS were 2.7 and 5.3 months, respectively, for arm A, and 3.8 and 6.9 months, respectively, for arm B. Objective response rate was 18% for both arms. Patients with high serum level of Hsp27 represented a poor-prognosis subgroup who may have derived modest benefit from addition of apatorsen. CONCLUSION: Addition of apatorsen to chemotherapy does not improve outcomes in unselected patients with metastatic pancreatic cancer in the first-line setting, although a trend toward prolonged PFS and OS in patients with high baseline serum Hsp27 suggests this therapy may warrant further evaluation in this subgroup.

13 Clinical Trial A Phase I Study of FOLFIRINOX Plus IPI-926, a Hedgehog Pathway Inhibitor, for Advanced Pancreatic Adenocarcinoma. 2016

Ko, Andrew H / LoConte, Noelle / Tempero, Margaret A / Walker, Evan J / Kate Kelley, R / Lewis, Stephanie / Chang, Wei-Chou / Kantoff, Emily / Vannier, Michael W / Catenacci, Daniel V / Venook, Alan P / Kindler, Hedy L. ·From the *Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA; †Division of Hematology/Oncology, University of Wisconsin, Madison, WI; ‡Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; and §Department of Radiology and ∥Division of Hematology/Oncology, University of Chicago, Chicago, IL. ·Pancreas · Pubmed #26390428.

ABSTRACT: OBJECTIVES: In mouse models of pancreatic cancer, IPI-926, an oral Hedgehog inhibitor, increases chemotherapy delivery by depleting tumor-associated stroma. This multicenter phase Ib study evaluated IPI-926 in combination with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) in patients with advanced pancreatic cancer. METHODS: Patients were treated with once-daily IPI-926 plus FOLFIRINOX. A 3 + 3 dose escalation design was used, with cohort expansion at the maximum tolerated dose. A subset of patients underwent perfusion computed tomography to assess changes in tumor perfusion. RESULTS: The maximum tolerated dose was identified 1 dose level below standard FOLFIRINOX. Common treatment-related adverse events included liver function test abnormalities, neuropathy, nausea/vomiting, and diarrhea. Objective response rate was high (67%), and patients receiving IPI-926 maintenance showed further declines in CA19-9 levels even after FOLFIRINOX discontinuation. Treatment did not result in consistent increases in tumor perfusion. The study closed early when a separate phase II trial of IPI-926 plus gemcitabine indicated detrimental effects of this combination. CONCLUSIONS: This is the first study to demonstrate the feasibility of using FOLFIRINOX as the chemotherapeutic backbone in a clinical trial design. Although robust antitumor activity and acceptable safety were observed with the addition of IPI-926 to this regimen, future development of Hedgehog inhibitors in pancreatic cancer seems unlikely.

14 Clinical Trial A Multicenter, Open-Label Phase II Clinical Trial of Combined MEK plus EGFR Inhibition for Chemotherapy-Refractory Advanced Pancreatic Adenocarcinoma. 2016

Ko, Andrew H / Bekaii-Saab, Tanios / Van Ziffle, Jessica / Mirzoeva, Olga M / Joseph, Nancy M / Talasaz, AmirAli / Kuhn, Peter / Tempero, Margaret A / Collisson, Eric A / Kelley, R Kate / Venook, Alan P / Dito, Elizabeth / Ong, Anna / Ziyeh, Sharvina / Courtin, Ryan / Linetskaya, Regina / Tahiri, Sanaa / Korn, W Michael. ·Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. andrewko@medicine.ucsf.edu. · Ohio State University Comprehensive Cancer Center, Columbus, Ohio. · Department of Pathology, University of California San Francisco, San Francisco, California. · Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. · Guardant Health, Inc., Redwood City, California. · University of Southern California, Los Angeles, California. ·Clin Cancer Res · Pubmed #26251290.

ABSTRACT: PURPOSE: On the basis of preclinical evidence of synergistic activity between MEK and EGFR inhibitors in pancreatic ductal adenocarcinoma (PDAC), we evaluated the safety and efficacy of selumetinib, a MEK1/2 inhibitor, plus erlotinib in patients with previously treated advanced PDAC. EXPERIMENTAL DESIGN: In this single-arm phase II trial, eligible patients received the combination of erlotinib 100 mg plus selumetinib 100 mg daily in 3-week cycles. Study assessments included measurement of clinical outcomes, with a primary endpoint of overall survival, and exploration of potential molecular predictors of treatment benefit. RESULTS: Forty-six patients were enrolled and received a median of two cycles (range, 1-7). Although no objective responses were observed, 19 patients (41%) showed evidence of stable disease for ≥6 weeks, and 13 of 34 patients (38%) had a CA19-9 decline ≥50%. Median progression-free survival was 1.9 months [95% confidence interval (CI), 1.4-3.3 months], with a median overall survival of 7.3 months (95% CI, 5.2-8.0 months). Common adverse events included rash, diarrhea, and nausea/vomiting. Patients with tumors exhibiting an epithelial phenotype (demonstrated by a high level of E-cadherin expression) were more likely to be sensitive to study treatment. Tumor-derived DNA was detectable in plasma from the majority of patients using next-generation digital DNA sequencing, and its relative abundance correlated with tumor burden. CONCLUSIONS: A therapeutic strategy of dual targeted inhibition of the MEK and EGFR pathways shows modest antitumor activity in pancreatic cancer. Specific molecular subtypes may derive greatest benefit from this combination. Further exploration, both with more potent MEK inhibitors and in molecularly enriched patient subsets, is warranted.

15 Clinical Trial A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. 2013

Ko, A H / Tempero, M A / Shan, Y-S / Su, W-C / Lin, Y-L / Dito, E / Ong, A / Wang, Y-W / Yeh, C G / Chen, L-T. ·Division of Hematology/Oncology, Comprehensive Cancer Center, University of California, San Francisco, 1600 Divisadero Street, San Francisco, CA 94115, USA. andrewko@medicine.ucsf.edu ·Br J Cancer · Pubmed #23880820.

ABSTRACT: BACKGROUND: PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer. METHODS: Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ≥70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m(-2) was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS(3-month)). RESULTS: A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS(3-month) of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively. CONCLUSION: PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.

16 Clinical Trial A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. 2012

Ko, Andrew H / Truong, Thach-Giao / Kantoff, Emily / Jones, Kimberly A / Dito, Elizabeth / Ong, Anna / Tempero, Margaret A. ·Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 94115, USA. andrewko@medicine.ucsf.edu ·Cancer Chemother Pharmacol · Pubmed #23053263.

ABSTRACT: BACKGROUND: Substantial antitumor activity has previously been demonstrated with the addition of nab-paclitaxel (Abraxane [Celgene, Summit, NJ]), an albumin-bound formulation of paclitaxel, to gemcitabine in patients with advanced pancreatic cancer. Given preclinical evidence of synergy when a fluoropyrimidine is added to gemcitabine plus a taxane in a sequence-specific schedule, we conducted a phase I study to evaluate the combination of nab-paclitaxel, gemcitabine, and capecitabine administered biweekly in patients with metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with previously untreated metastatic pancreatic cancer and an ECOG performance status of 0-1 were eligible to participate. Study design utilized a 3 + 3 dose-escalation schema, with expanded cohort at maximum-tolerated dose (MTD). Treatment was administered in 14-day cycles, with capecitabine given on days 1-7 and both gemcitabine (at fixed-dose rate infusion) and nab-paclitaxel on day 4 of each cycle. Dose-limiting toxicity (DLT) definitions included grade 3-4 hematologic toxicities and grade 2-4 hand-foot syndrome, neuropathy, or diarrhea. RESULTS: Fifteen patients were enrolled across two dose levels. Final MTD was established at nab-paclitaxel 100 mg/m(2), gemcitabine 750 mg/m(2), and capecitabine 750 mg/m(2) twice daily. Patients received a median of four treatment cycles (range 1-16). The most frequent adverse events (any grade) for the entire study cohort included fatigue, rash/hand-foot syndrome, nausea/vomiting, diarrhea, neuropathy, and elevated liver function tests. Ten patients (66.7 %) experienced at least one grade 3-4 adverse event. Grade 3-4 hematologic toxicities were uncommon. Two of 14 evaluable patients (14.3 %) exhibited a partial response, and 6 of 12 patients (50 %) with elevated CA19-9 at baseline had a ≥50 % biomarker decline. CONCLUSION: While well tolerated overall, this regimen demonstrated only modest antitumor activity in patients with metastatic pancreatic cancer. Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of gemcitabine/nab-paclitaxel. The lower doses used in the current study suggest that dose intensity may be a critical aspect to optimize multidrug regimens.

17 Clinical Trial Optimizing the administration of fixed-dose rate gemcitabine plus capecitabine using an alternating-week schedule: a dose finding and early efficacy study in advanced pancreatic and biliary carcinomas. 2012

Ko, Andrew H / Espinoza, Anne M / Jones, Kimberly A / Venook, Alan P / Bergsland, Emily K / Kelley, Robin K / Dito, Elizabeth / Ong, Anna / Hanover, Cherry S / Coakley, Fergus V / Tempero, Margaret A. ·Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. andrewko@medicine.ucsf.edu ·Am J Clin Oncol · Pubmed #21552099.

ABSTRACT: OBJECTIVES: This multisite study sought to optimize the dosing, schedule, and administration of fixed-dose rate (FDR) gemcitabine plus capecitabine for advanced pancreatic and biliary tract cancers using an alternating-week dose schedule of both agents. METHODS: Patients with previously untreated advanced pancreatic and biliary tract cancers with Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. For the dose-finding portion, a standard 3+3 dose-escalation schema was used, with the gemcitabine dose kept at 1000 mg/m(2) administered by FDR (10 mg/m(2)/min) on day 1 of each 14-day cycle, and capecitabine given on days 1 to 7 at doses ranging from 800 to 1500 mg/m(2) twice daily. Primary study objective was determination of maximum tolerated dose (MTD). The cohort at MTD was expanded for further efficacy assessment. RESULTS: A total of 45 patients (median age 61 y; 93% pancreatic/7% biliary; 84% with metastatic disease) were enrolled. Median number of cycles received was 11.5. The MTD using this dose schedule was FDR gemcitabine 1000 mg/m(2) plus capecitabine 1000 mg/m(2) bid, due to a high incidence of late hand-foot syndrome observed at the next higher dose level. Most common nonhematologic adverse events related to treatment included nausea/vomiting (overall rate, 64%; all grade 1/2) and hand-foot syndrome (overall rate, 60%; grade 3, 22%). The incidence of grade 3/4 hematologic adverse events was 24%. Six of 41 evaluable patients (14.6%) had a partial response; 18 of 31 patients (58%) with elevated baseline CA 19-9 level had ≥50% biomarker decline during treatment. Estimated median time to tumor progression and overall survival were 5.5 and 9.8 months, respectively (5.5 and 10.1 mo in the metastatic pancreatic cancer cohort). CONCLUSIONS: This dosing schedule of FDR gemcitabine plus capecitabine is active in patients with advanced pancreatobiliary cancers. Given its favorable toxicity profile and convenience, this regimen represents an appropriate front-line option for this patient population and may serve as the foundation on which new investigational agents are added in future trial design.

18 Clinical Trial A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory metastatic pancreatic cancer. 2010

Ko, Andrew H / Venook, Alan P / Bergsland, Emily K / Kelley, R Kate / Korn, W Michael / Dito, Elizabeth / Schillinger, Brian / Scott, Janet / Hwang, Jimmy / Tempero, Margaret A. ·University of California at San Francisco Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, 4th Floor, Box 1705, San Francisco, CA 94115, USA. andrewko@medicine.ucsf.edu ·Cancer Chemother Pharmacol · Pubmed #20130876.

ABSTRACT: PURPOSE: No standard of care exists for patients with metastatic pancreatic cancer following progression on first-line chemotherapy. Based on potential for additive or synergistic activity by concurrent inhibition of VEGF and EGFR, we conducted a phase II study evaluating the combination of bevacizumab plus erlotinib in this patient population. METHODS: Patients with metastatic pancreatic adenocarcinoma, ECOG performance status 0-1, and previous exposure to 1-3 systemic therapies (at least one gemcitabine-based) were eligible. Treatment consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily. RESULTS: Thirty-six patients were enrolled, including eight who had previously received VEGF-targeted therapy and nine prior erlotinib. Median number of treatment cycles was 2 (range, 1-7). Common toxicities included rash (72%), diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). One patient demonstrated partial response and seven others stable disease for >2 cycles. CA19-9 decline ≥25% was observed in 4/26 patients with baseline levels >2x ULN. Estimated median time to progression was 40 days (95% CI, 35-41 days) and median survival 102 days (95% CI, 74-117 days), with a 6-month survival rate of 22%. Baseline concentration of circulating endothelial cells (CD45(-)/CD34(+)/CD31(+)) was inversely associated with overall survival. CONCLUSIONS: The combination of bevacizumab and erlotinib is safe but relatively ineffective in patients with gemcitabine-refractory metastatic pancreatic cancer. Future studies should focus on refining subsets of patients in this challenging population likely to benefit from treatment beyond first-line.

19 Clinical Trial Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904. 2009

Kulke, Matthew H / Tempero, Margaret A / Niedzwiecki, Donna / Hollis, Donna R / Kindler, Hedy L / Cusnir, Michael / Enzinger, Peter C / Gorsch, Stefan M / Goldberg, Richard M / Mayer, Robert J. ·Dana-Farber Cancer Institute, Boston, MA, USA. matthew_kulke@dfci.harvard.edu ·J Clin Oncol · Pubmed #19858396.

ABSTRACT: PURPOSE: The relative value of gemcitabine-based combination chemotherapy therapy and prolonged infusions of gemcitabine in patients with advanced pancreatic cancer remains controversial. We explored the efficacy and toxicity of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in a multi-institutional, randomized, phase II study. PATIENTS AND METHODS: Patients with metastatic pancreatic cancer were randomly assigned to one of the following four regimens: gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 with cisplatin 50 mg/m(2) on days 1 and 15 (arm A); gemcitabine 1,500 mg/m(2) at a rate of 10 mg/m(2)/min on days 1, 8, and 15 (arm B); gemcitabine 1,000 mg/m(2) with docetaxel 40 mg/m(2) on days 1 and 8 (arm C); or gemcitabine 1,000 mg/m(2) with irinotecan 100 mg/m(2) on days 1 and 8 (arm D). Patients were observed for response, toxicity, and survival. Results Two hundred fifty-nine patients were enrolled onto the study, of whom 245 were eligible and received treatment. Anticipated rates of myelosuppression, fatigue, and expected regimen-specific toxicities were observed. The overall tumor response rates were 12% to 14%, and the median overall survival times were 6.4 to 7.1 months among the four regimens. CONCLUSION: Gemcitabine/cisplatin, fixed dose rate gemcitabine, gemcitabine/docetaxel, and gemcitabine/irinotecan have similar antitumor activity in metastatic pancreatic cancer. In light of recent negative randomized studies directly comparing several of these regimens with standard gemcitabine, none of these approaches can be recommended for routine use in patients with this disease.

20 Article Referral frequency, attrition rate, and outcomes of germline testing in patients with pancreatic adenocarcinoma. 2019

Walker, Evan J / Carnevale, Julia / Pedley, Christina / Blanco, Amie / Chan, Salina / Collisson, Eric A / Tempero, Margaret A / Ko, Andrew H. ·Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA, 94143, USA. · Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 550 16th Street, San Francisco, CA, 94143, USA. · Cancer Genetics and Prevention Program, University of California, San Francisco, San Francisco, CA, 94143, USA. · Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA, 94143, USA. Andrew.ko@ucsf.edu. · Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 550 16th Street, San Francisco, CA, 94143, USA. Andrew.ko@ucsf.edu. ·Fam Cancer · Pubmed #30267352.

ABSTRACT: Hereditary predisposition is estimated to account for 10% of all pancreatic cancer cases. However, referral patterns and clinical workflow for germline testing in this disease differ significantly by institution, and many at-risk patients may not undergo appropriate counseling and testing. We undertook an analysis of patients diagnosed with pancreatic cancer (PDAC) who were referred to the Clinical Genetics program of a high-volume academic center over a 3-year period to assess referral frequency, evaluate the yield of germline testing in this selected patient cohort, and elucidate the reasons individuals did not undergo recommended germline testing. Medical records of patients with PDAC referred for genetic counseling between January 2015 and October 2017 were reviewed for demographic, medical/family history, and disease-specific data. If testing did not occur, reasons were documented. Genetic test results were categorized as negative, variants of unknown significance, or established pathogenic mutations. Descriptive statistics included means with standard deviations; associations were analyzed with t test and Fisher's exact test. 32% (137 of 432) of PDAC patients were referred for genetic counseling, but only 64% attended their appointment and 60% ultimately underwent germline testing. Common reasons for attrition included worsening disease severity, lack of patient follow-up, insurance concerns, and logistic/travel challenges. Pathogenic germline mutations were detected in 20% (16 of 82) of patients tested, distributed across races/ethnicities, and significantly associated with younger age and positive family history of breast cancer. PDAC patients frequently do not undergo genetic counseling/germline testing despite appropriate referrals, highlighting a need to develop streamlined processes to engage more patients in testing, especially those with high-risk features.

21 Article Early Response Assessment in Pancreatic Ductal Adenocarcinoma Through Integrated PET/MRI. 2018

Wang, Zhen J / Behr, Spencer / Consunji, Martin V / Yeh, Benjamin M / Ohliger, Michael A / Gao, Kenneth / Ko, Andrew H / Cinar, Pelin / Tempero, Margaret A / Collisson, Eric A. ·1 Department of Radiology and Biomedical Imaging, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA 94143. · 2 Department of Medicine, University of California San Francisco, San Francisco, CA. ·AJR Am J Roentgenol · Pubmed #30063366.

ABSTRACT: OBJECTIVE: The purpose of this study is to investigate early changes in SUBJECTS AND METHODS: Thirteen patients with advanced PDAC underwent integrated FDG PET/MRI before and 4 weeks after treatment initiation. Patients were classified as responders or nonresponders according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at subsequent CT performed 8-12 weeks after treatment initiation. Changes in the primary tumor's maximum standardized uptake value (SUV RESULTS: Seven patients had a partial response according to RECIST, and six did not. Responders displayed significantly greater decreases in MTV (p = 0.003) and TLG (p = 0.006) in the primary pancreatic tumor at 4 weeks. Responders also displayed a greater increase in the mean (p = 0.004) and minimum (p = 0.024) ADC of the primary tumors. Tumor size change at 4 weeks was not significantly different between responders and nonresponders (p = 0.11). PET responders enjoyed longer progression-free survival (PFS) (p = 0.0004) and overall survival (OS) (p = 0.013) than did nonresponders, using either a 60% reduction in MTV or 65% reduction in TLG as a threshold. MRI responders had significantly longer PFS (p = 0.0002) and OS (p = 0.027) than did nonresponders, using a 20% increase in either mean or minimum ADC as a threshold. CONCLUSION: Integrated PET/MRI can provide early response assessment in patients with advanced PDAC, thus potentially allowing early treatment adaptation in nonresponders.

22 Article Active Systemic Treatment of Pancreatic Cancer. 2017

Tempero, Margaret. ·Presented by Margaret Tempero, MD, Professor of Medicine and Director of the University of California San Francisco (UCSF) Pancreas Center, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California. ·J Natl Compr Canc Netw · Pubmed #28515255.

ABSTRACT: By 2020, pancreatic cancer is expected to be the second most common cause of cancer-related death, exceeded only by lung cancer. During her presentation at the NCCN 22nd Annual Conference, Dr. Margaret Tempero offered an update on the current state of systemic treatment of pancreatic cancer, focusing on resectable/borderline resectable, locally advanced, and metastatic disease.

23 Article Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer. 2017

Capello, Michela / Bantis, Leonidas E / Scelo, Ghislaine / Zhao, Yang / Li, Peng / Dhillon, Dilsher S / Patel, Nikul J / Kundnani, Deepali L / Wang, Hong / Abbruzzese, James L / Maitra, Anirban / Tempero, Margaret A / Brand, Randall / Firpo, Matthew A / Mulvihill, Sean J / Katz, Matthew H / Brennan, Paul / Feng, Ziding / Taguchi, Ayumu / Hanash, Samir M. ·Departments of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · International Agency for Research on Cancer (IARC) Lyon, France. · Division of Medical Oncology, Duke University, Durham, NC, USA. · Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Pancreas Center, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA · Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA. · Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·J Natl Cancer Inst · Pubmed #28376157.

ABSTRACT: Background: CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early-stage disease. We and others have identified protein biomarker candidates that have the potential to complement CA19-9. We have carried out sequential validations starting with 17 protein biomarker candidates to determine which markers and marker combination would improve detection of early-stage disease compared with CA19-9 alone. Methods: Candidate biomarkers were subjected to enzyme-linked immunosorbent assay based sequential validation using independent multiple sample cohorts consisting of PDAC cases (n = 187), benign pancreatic disease (n = 93), and healthy controls (n = 169). A biomarker panel for early-stage PDAC was developed based on a logistic regression model. All statistical tests for the results presented below were one-sided. Results: Six out of the 17 biomarker candidates and CA19-9 were validated in a sample set consisting of 75 PDAC patients, 27 healthy subjects, and 19 chronic pancreatitis patients. A second independent set of 73 early-stage PDAC patients, 60 healthy subjects, and 74 benign pancreatic disease patients (combined validation set) yielded a model that consisted of TIMP1, LRG1, and CA19-9. Additional blinded testing of the model was done using an independent set of plasma samples from 39 resectable PDAC patients and 82 matched healthy subjects (test set). The model yielded areas under the curve (AUCs) of 0.949 (95% confidence interval [CI] = 0.917 to 0.981) and 0.887 (95% CI = 0.817 to 0.957) with sensitivities of 0.849 and 0.667 at 95% specificity in discriminating early-stage PDAC vs healthy subjects in the combined validation and test sets, respectively. The performance of the biomarker panel was statistically significantly improved compared with CA19-9 alone (P < .001, combined validation set; P = .008, test set). Conclusion: The addition of TIMP1 and LRG1 immunoassays to CA19-9 statistically significantly improves the detection of early-stage PDAC.

24 Article Hypermutation In Pancreatic Cancer. 2017

Humphris, Jeremy L / Patch, Ann-Marie / Nones, Katia / Bailey, Peter J / Johns, Amber L / McKay, Skye / Chang, David K / Miller, David K / Pajic, Marina / Kassahn, Karin S / Quinn, Michael C J / Bruxner, Timothy J C / Christ, Angelika N / Harliwong, Ivon / Idrisoglu, Senel / Manning, Suzanne / Nourse, Craig / Nourbakhsh, Ehsan / Stone, Andrew / Wilson, Peter J / Anderson, Matthew / Fink, J Lynn / Holmes, Oliver / Kazakoff, Stephen / Leonard, Conrad / Newell, Felicity / Waddell, Nick / Wood, Scott / Mead, Ronald S / Xu, Qinying / Wu, Jianmin / Pinese, Mark / Cowley, Mark J / Jones, Marc D / Nagrial, Adnan M / Chin, Venessa T / Chantrill, Lorraine A / Mawson, Amanda / Chou, Angela / Scarlett, Christopher J / Pinho, Andreia V / Rooman, Ilse / Giry-Laterriere, Marc / Samra, Jaswinder S / Kench, James G / Merrett, Neil D / Toon, Christopher W / Epari, Krishna / Nguyen, Nam Q / Barbour, Andrew / Zeps, Nikolajs / Jamieson, Nigel B / McKay, Colin J / Carter, C Ross / Dickson, Euan J / Graham, Janet S / Duthie, Fraser / Oien, Karin / Hair, Jane / Morton, Jennifer P / Sansom, Owen J / Grützmann, Robert / Hruban, Ralph H / Maitra, Anirban / Iacobuzio-Donahue, Christine A / Schulick, Richard D / Wolfgang, Christopher L / Morgan, Richard A / Lawlor, Rita T / Rusev, Borislav / Corbo, Vincenzo / Salvia, Roberto / Cataldo, Ivana / Tortora, Giampaolo / Tempero, Margaret A / Anonymous5740887 / Hofmann, Oliver / Eshleman, James R / Pilarsky, Christian / Scarpa, Aldo / Musgrove, Elizabeth A / Gill, Anthony J / Pearson, John V / Grimmond, Sean M / Waddell, Nicola / Biankin, Andrew V. ·The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales Australia, Liverpool, New South Wales, Australia; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Genetic and Molecular Pathology, Adelaide, South Australia, Australia; School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; South Eastern Area Laboratory Services Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia; Sonic Genetics, Douglass Hanly Moir Pathology, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Macarthur Cancer Therapy Centre, Campbelltown Hospital, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Department of Anatomical Pathology, SydPath, St Vincent's Hospital, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia. · Department of Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. · Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; School of Medicine, Western Sydney University, Penrith, New South Wales, Australia. · Department of Surgery, Fiona Stanley Hospital, Murdoch, Washington. · Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia. · Department of Surgery, Princess Alexandra Hospital, Woollongabba, Queensland, Australia. · School of Surgery, University of Western Australia, Australia and St John of God Pathology, Subiaco, Washington. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. · Department of Pathology, Southern General Hospital, Greater Glasgow & Clyde National Health Service, Glasgow, United Kingdom. · Greater Glasgow and Clyde Bio-repository, Pathology Department, Queen Elizabeth University Hospital, Glasgow, United Kingdom. · Cancer Research UK Beatson Institute, Glasgow, United Kingdom; Institute for Cancer Science, University of Glasgow, Glasgow, United Kingdom. · Universitätsklinikum Erlangen, Erlangen, Germany. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland. · ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Department of Medicine, University and Hospital Trust of Verona, Verona, Italy. · Division of Hematology and Oncology, University of California, San Francisco, California. · Australian Pancreatic Cancer Genome Initiative. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom. · Universitätsklinikum Erlangen, Department of Surgery, University of Erlangen-Nueremberg, Germany. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia. · The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; University of Melbourne Centre for Cancer Research, The University of Melbourne, Melbourne, Victoria, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Electronic address: nic.waddell@qimrberghofer.edu.au. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales Australia, Liverpool, New South Wales, Australia; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. Electronic address: andrew.biankin@glasgow.ac.uk. ·Gastroenterology · Pubmed #27856273.

ABSTRACT: Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

25 Article Preoperative FOLFIRINOX for borderline resectable pancreatic cancer: Is radiation necessary in the modern era of chemotherapy? 2016

Kim, Sunhee S / Nakakura, Eric K / Wang, Zhen J / Kim, Grace E / Corvera, Carlos U / Harris, Hobart W / Kirkwood, Kimberly S / Hirose, Ryutaro / Tempero, Margaret A / Ko, Andrew H. ·Division of Hematology/Oncology, University of California San Francisco, San Francisco, California. · Department of Surgery, University of California San Francisco, San Francisco, California. eric.nakakura@ucsf.edu. · Department of Radiology, University of California San Francisco, San Francisco, California. · Department of Pathology, University of California San Francisco, San Francisco, California. · Department of Surgery, University of California San Francisco, San Francisco, California. · Division of Hematology/Oncology, University of California San Francisco, San Francisco, California. andrewko@medicine.ucsf.edu. ·J Surg Oncol · Pubmed #27444658.

ABSTRACT: BACKGROUND: No consensus exists regarding the optimal neoadjuvant treatment paradigm for patients with borderline resectable pancreatic cancer (BRPC), including the respective roles of chemotherapy and radiation. METHODS: We performed a retrospective analysis, including detailed pathologic and radiologic review, of pancreatic cancer patients undergoing FOLFIRINOX, with or without radiation therapy (RT), prior to surgical resection at a high-volume academic center over a 4-year period. RESULTS: Of 26 patients meeting inclusion criteria, 22 (84.6%) received FOLFIRINOX alone without RT (median number of treatment cycles = 9). The majority of patients met formal radiographic criteria for BRPC, with the superior mesenteric vein representing the most common vessel involved. R0 resection rate was 90.9%, with 12 patients (54.5%) requiring vascular reconstruction. Treatment response was classified as moderate or marked in 16 patients (72.7%) according to the College of American Pathologists grading system. Estimated median disease-free and overall survival rates are 22.6 months and not reached (NR), respectively. CONCLUSIONS: This is one of the largest series to describe the use of neoadjuvant FOLFIRINOX, without radiation therapy, in patients with BRPC undergoing surgical resection. Given the high R0 resection rates and favorable clinical outcomes with chemotherapy alone, this strategy should be further assessed in prospective study design. J. Surg. Oncol. 2016;114:587-596. © 2016 Wiley Periodicals, Inc.

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