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pancreatic adenocarcinoma chemotherapy

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https://www.readbyqxmd.com/read/29243123/response-assessment-in-pancreatic-ductal-adenocarcinoma-role-of-imaging
#1
Vinit Baliyan, Hamed Kordbacheh, Anushri Parakh, Avinash Kambadakone
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal (GI) malignancy with poor 5-year survival rate. Advances in surgical techniques and introduction of novel combination chemotherapy and radiation therapy regimens have necessitated the need for biomarkers for assessment of treatment response. Conventional imaging methods such as RECIST have been used for response evaluation in clinical trials particularly in patients with metastatic PDAC. However, the role of these approaches for assessing response to loco-regional and systemic therapies is limited due to complex morphological and histological nature of PDAC...
December 14, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/29232340/ablative-therapies-for-locally-advanced-pancreatic-cancer
#2
Rupen Shah, Katherine T Ostapoff, Boris Kuvshinoff, Steven N Hochwald
The vast majority of patients who present with pancreatic adenocarcinoma have locally advanced or metastatic disease at the time of presentation without possibility of cure. Although in recent years there have been some new promising chemotherapy regimens that improve overall survival by a few months, the prognosis remains dismal. There is, however, a subset of patients who experience durable stable disease or partial responses after initial courses of chemotherapy with locally advanced disease. In these select patients, there remains interest in local ablative therapy with or without resection as a means for local control, palliation of symptoms, and possible improved survival...
January 2018: Pancreas
https://www.readbyqxmd.com/read/29229121/efficacy-of-completion-pancreatectomy-for-recurrence-of-adenocarcinoma-in-the-remnant-pancreas
#3
Yusuke Nakayama, Motokazu Sugimoto, Naoto Gotohda, Masaru Konishi, Shinichiro Takahashi
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, with a high rate of recurrence even after complete surgical resection. The aim of this study was to investigate the impact of completion pancreatectomy (CP) on the clinical course of patients with recurrent PDAC in the remnant pancreas. MATERIALS AND METHODS: Between January 2008 and December 2014, 194 patients underwent curative-intent surgical resection (initial pancreatectomy [IP]) for PDAC at our institution...
January 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29223478/phase-ii-trial-of-veliparib-in-patients-with-previously-treated-brca-mutated-pancreas-ductal-adenocarcinoma
#4
Maeve A Lowery, David P Kelsen, Marinela Capanu, Sloane C Smith, Jonathan W Lee, Zsofia K Stadler, Malcolm J Moore, Hedy L Kindler, Talia Golan, Amiel Segal, Hannah Maynard, Ellen Hollywood, MaryEllen Moynahan, Erin E Salo-Mullen, Richard Kinh Gian Do, Alice P Chen, Kenneth H Yu, Laura H Tang, Eileen M O'Reilly
PURPOSE: BRCA-associated cancers have increased sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre phase II trial evaluated the response rate of veliparib in patients with previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC). METHODS: Patients with stage III/IV PDAC and known germline BRCA1/2 or PALB2 mutation, 1-2 lines of treatment, Eastern Cooperative Oncology Group 0-2, were enrolled...
December 7, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29223362/autophagy-inhibition-in-pancreatic-adenocarcinoma
#5
REVIEW
Brian A Boone, Herbert J Zeh, Nathan Bahary
Although some progress has been made in recent years with the development of more effective chemotherapy regimens, new treatment approaches are needed to improve outcomes for patients with pancreatic adenocarcinoma. The cellular process of autophagy, a cell survival mechanism that allows cancer cells to survive the hazardous conditions of the tumor microenvironment and treatment, has emerged as a viable target in pancreatic cancer. We review the mechanism of autophagy, its role in pancreatic carcinogenesis, the preclinical and clinical evidence supporting targeting autophagy in patients with pancreatic adenocarcinoma, and areas of future investigation that hold promise for improving this treatment approach...
October 28, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29221990/molecular-and-cellular-mechanisms-of-chemoresistance-in-pancreatic-cancer
#6
REVIEW
Aleksandra Adamska, Omar Elaskalani, Aikaterini Emmanouilidi, Minkyoung Kim, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available options are surgery, embolization, radiation, chemotherapy, immunotherapy and use of other more targeted drugs. In this review, we describe the cellular and molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE (nab-Paclitaxel), which have shown a survival benefit, although modest, for pancreatic cancer patients...
November 22, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29216749/impact-of-palliative-chemotherapy-and-travel-distance-on-hospice-referral-in-patients-with-stage-iv-pancreatic-cancer-a-retrospective-analysis-within-a-veterans-administration-medical-center
#7
Jennifer M Duff, Ryan M Thomas
BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (mPDAC) has a poor prognosis despite chemotherapy advancements. Although hospice utilization has increased, timing of referral is not always optimal. AIM: To investigate whether palliative chemotherapy and travel distance to the treatment center impact hospice referral patterns in veterans of the US military in order to identify potential areas for improving referral timing. DESIGN: Demographic and clinical data were collected retrospectively according to the timing of hospice referral...
January 1, 2017: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/29216209/preliminary-study-of-tumor-heterogeneity-in-imaging-predicts-two-year-survival-in-pancreatic-cancer-patients
#8
Jayasree Chakraborty, Liana Langdon-Embry, Kristen M Cunanan, Joanna G Escalon, Peter J Allen, Maeve A Lowery, Eileen M O'Reilly, Mithat Gönen, Richard G Do, Amber L Simpson
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy...
2017: PloS One
https://www.readbyqxmd.com/read/29212734/predictors-of-response-and-survival-in-locally-advanced-adenocarcinoma-of-the-pancreas-following-neoadjuvant-gtx-with-or-without-radiation-therapy
#9
William H Sherman, Elizabeth Hecht, David Leung, Kyung Chu
LESSONS LEARNED: There is no presenting parameter that predicts the success of neoadjuvant therapy for pancreatic cancer.Despite the images on scans following neoadjuvant therapy, all patients should be evaluated, because inflammation following radiation therapy (RT) may overstate the extent of tumor and vascular involvement. BACKGROUND: In patients presenting with locally advanced pancreatic adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed presenting tumor size, extent of vascular involvement, tumor markers, response to neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without additional chemoradiotherapy with GX on R0 resection rates (≥2 mm margins), and survival...
December 6, 2017: Oncologist
https://www.readbyqxmd.com/read/29209626/neovascular-prostate-specific-membrane-antigen-expression-is-associated-with-improved-overall-survival-under-palliative-chemotherapy-in-patients-with-pancreatic-ductal-adenocarcinoma
#10
Katharina Stock, Konrad Steinestel, Rebekka Wiesch, Jan-Henrik Mikesch, Anna Hansmeier, Marcel Trautmann, Nora Beller, Jan Rehkämper, Eva Wardelmann, Birthe Heitkötter, Wolfgang Hartmann, Jan Sperveslage, Sebastian Huss
Aims: Expression of PSMA (prostate-specific membrane antigen) has been demonstrated in various cancers, including pancreatic ductal adenocarcinoma (PDAC). However, PSMA expression in PDAC-associated neovasculature has so far not been systematically analyzed. Methods and Results: We analyzed PSMA expression in 81 PDAC tissue samples from 61 patients. Microvessel density (MVD) was assessed by software-based image analysis and showed a mean MVD of 63.7 microvessels/0...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29207968/palliative-chemotherapy-for-pancreatic-adenocarcinoma-a-retrospective-cohort-analysis-of-efficacy-and-toxicity-of-the-folfirinox-regimen-focusing-on-the-older-patient
#11
Anne Katrin Berger, Georg Martin Haag, Martin Ehmann, Anne Byl, Dirk Jäger, Christoph Springfeld
BACKGROUND: Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX. METHODS: We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients...
December 6, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29199604/mirna-a-diagnostic-and-therapeutic-tool-for-pancreatic-cancer
#12
Muhammad Imran Qadir, Arooj Faheem
Pancreatic ductal adenocarcinoma (PDAC) is fatal disease and one of the major causes of death among cancer patients. Diagnosis of PDAC during the early stages of cancer using ultrasounds and blood tests is difficult and chemotherapies alone for treating cancers are not very effective. MicroRNAs (miRNAs), small non-coding RNAs that alter the expression of genes in many processes, have been identified to play a significant role in pancreatic cancer regulation. miRNAs are classified as oncomiRs (tumor inducers) and tumor suppressor miRNAs...
2017: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29196965/metabolomic-prediction-of-treatment-outcome-in-pancreatic-ductal-adenocarcinoma-patients-receiving-gemcitabine
#13
Lee Cheng Phua, Shixu Goh, David Wai Meng Tai, Wei Qiang Leow, Syed Muhammad Fahmy Alkaff, Chung Yip Chan, Juinn Huar Kam, Tony Kiat Hon Lim, Eric Chun Yong Chan
PURPOSE: Resistance to gemcitabine remains a key challenge in the treatment of pancreatic ductal adenocarcinoma (PDAC), necessitating the constant search for effective strategies for a priori prediction of clinical outcome. While the existing studies focused on aberration of drug disposition genes and proteins as molecular predictors of gemcitabine treatment outcomes, the metabolic aberration associated with chemoresistance in clinical PDAC has been neglected. This exploratory study investigated the potential role of tissue metabolomics in characterizing the clinical treatment outcome of gemcitabine therapy...
December 1, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29196437/targeting-both-tumour-associated-cxcr2-neutrophils-and-ccr2-macrophages-disrupts-myeloid-recruitment-and-improves-chemotherapeutic-responses-in-pancreatic-ductal-adenocarcinoma
#14
Timothy M Nywening, Brian A Belt, Darren R Cullinan, Roheena Z Panni, Booyeon J Han, Dominic E Sanford, Ryan C Jacobs, Jian Ye, Ankit A Patel, William E Gillanders, Ryan C Fields, David G DeNardo, William G Hawkins, Peter Goedegebuure, David C Linehan
OBJECTIVE: Chemokine pathways are co-opted by pancreatic adenocarcinoma (PDAC) to facilitate myeloid cell recruitment from the bone marrow to establish an immunosuppressive tumour microenvironment (TME). Targeting tumour-associated CXCR2+neutrophils (TAN) or tumour-associated CCR2+ macrophages (TAM) alone improves antitumour immunity in preclinical models. However, a compensatory influx of an alternative myeloid subset may result in a persistent immunosuppressive TME and promote therapeutic resistance...
December 1, 2017: Gut
https://www.readbyqxmd.com/read/29191829/st6gal-i-sialyltransferase-promotes-chemoresistance-in-pancreatic-ductal-adenocarcinoma-by-abrogating-gemcitabine-mediated-dna-damage
#15
Asmi Chakraborty, Kaitlyn A Dorsett, Hoa Q Trummell, Eddy S Yang, Patsy G Oliver, James A Bonner, Donald J Buchsbaum, Susan L Bellis
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Gemcitabine, as a single agent or in combination therapy, remains the frontline chemotherapy despite its limited efficacy due to de novo or acquired chemoresistance. There is an acute need to decipher mechanisms underlying chemoresistance and identify new targets to improve patient outcomes. Here we report a novel role for the ST6Gal-I sialyltransferase in gemcitabine resistance. Utilizing MiaPaCa-2 and BxPC-3 PDAC cells, we find that knockdown (KD) of ST6Gal-I expression, as well as removal of surface α2-6 sialic acids by neuraminidase, enhances gemcitabine-mediated cell death assessed via colonogenic assays and cleaved caspase 3 expression...
November 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29189327/the-pancreatic-cancer-microenvironment
#16
Stephanie K Dougan
Pancreatic ductal adenocarcinoma (PDAC) is composed of a minority of malignant cells within a microenvironment of extracellular matrix, fibroblasts, endothelial cells, and immune cells. Therapeutic failures of chemotherapy, targeted therapy, and immunotherapy have all been attributed to the PDAC microenvironment. In this review, we dissect the components of the microenvironment and explain how each cell type contributes to form a highly immunosuppressive, hypoxic, and desmoplastic cancer. New efforts in single-cell profiling will enable a better understanding of the composition of the microenvironment in primary and metastatic PDAC, as well as an understanding of how the microenvironment may respond to novel therapeutic approaches...
November 2017: Cancer Journal
https://www.readbyqxmd.com/read/29184680/stereotactic-body-radiotherapy-for-locally-advanced-unresectable-pancreatic-cancer-patterns-of-care-and-overall-survival
#17
Michael J Dohopolski, Scott M Glaser, John A Vargo, Goundappa K Balasubramani, Sushil Beriwal
Background: Unresectable pancreatic cancer remains a challenging disease to treat. Stereotactic body radiotherapy (SBRT) allows for a higher biologically equivalent dose in an abbreviated course more convenient for patients and the integration of systemic therapy. We sought to investigate utilization trends and survival outcomes for patients treated with pancreatic SBRT versus conventionally fractionated radiotherapy (CFRT). Methods: We engaged the National Cancer Database (NCDB) from 1998-2012 and identified locally-advanced unresectable patients with histologically confirmed, non-metastatic, pancreatic adenocarcinoma who received radiotherapy...
October 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29180759/nano-enabled-pancreas-cancer-immunotherapy-using-immunogenic-cell-death-and-reversing-immunosuppression
#18
Jianqin Lu, Xiangsheng Liu, Yu-Pei Liao, Felix Salazar, Bingbing Sun, Wen Jiang, Chong Hyun Chang, Jinhong Jiang, Xiang Wang, Anna M Wu, Huan Meng, Andre E Nel
While chemotherapy delivery by nanocarriers has modestly improved the survival prospects of pancreatic ductal adenocarcinoma (PDAC), additional engagement of the immune response could be game changing. We demonstrate a nano-enabled approach for accomplishing robust anti-PDAC immunity in syngeneic mice through the induction of immunogenic cell death (ICD) as well as interfering in the immunosuppressive indoleamine 2,3-dioxygenase (IDO) pathway. This is accomplished by conjugating the IDO inhibitor, indoximod (IND), to a phospholipid that allows prodrug self-assembly into nanovesicles or incorporation into a lipid bilayer that encapsulates mesoporous silica nanoparticles (MSNP)...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29180478/perioperative-spatiotemporally-coordinated-activation-of-t-and-nk-cells-prevents-recurrence-of-pancreatic-cancer
#19
Jennifer Brooks, Bettina Fleischmann-Mundt, Norman Woller, Julia Niemann, Silvia Ribback, Kristin Peters, Ihsan Ekin Demir, Nina Armbrecht, Guralp O Ceyhan, Michael P Manns, Thomas C Wirth, Stefan Kubicka, Gunter Bernhardt, Mark J Smyth, Diego F Calvisi, Engin Gürlevik, Florian Kühnel
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating cancer resistant to therapy, including checkpoint immunotherapies, and early tumor resection and (neo)adjuvant chemotherapy fails to improve a poor prognosis. In a transgenic mouse model of resectable PDAC, we investigated the coordinated activation of T and NK cells in addition to gemcitabine chemotherapy to prevent tumor recurrence. Only neoadjuvant, but not adjuvant treatment with a PD-1 antagonist effectively supported chemotherapy and suppressed local tumor recurrence and improved survival involving both NK and T cells...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29177608/identification-of-educational-gaps-among-oncologists-who-manage-patients-with-pancreatic-cancer
#20
Justin A Barnes, Melissa L Ellis, Sharon Hwang, Joan Emarine, Patti Merwin, Gregory D Salinas, Benjamin L Musher
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDA) is associated with poor outcomes and presents oncologists with a myriad of clinical challenges. This study was conducted to assess oncologists' practice patterns and to identify the greatest areas of need for future PDA continuing medical education (CME) programs. METHODS: Case vignettes have been validated as an effective tool to assess how physicians approach and treat a wide array of diseases. In order to assess practice patterns for resectable, locally advanced unresectable, and metastatic PDA, an online case vignette survey was distributed to practicing medical oncologists...
November 27, 2017: Journal of Gastrointestinal Cancer
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