text:
Remember, earlier this year Twitter was affected by a bug that showed retweets of random people on their timeline. Well, has been hit Twitter again with a bug that has left users experiencing issues with a fluctuating number of likes and retweets on their tweets.
Users around the world are facing issues with changes in 'retweet' and 'like' count-appearing to be much lower or higher. Twitter confirmed the glitch and said it was working to fix the problem.
Quick NetOne, Telecel, Africom, And Econet Airtime Recharge
If anything goes wrong, click here to enter your query.
WhatsApp Discussions
Click to join a Techzim WhatsApp group:
If you find the group full, please notify us on +263 715 071 199 and we'll update the link.

subset: commoncrawl


text:
Many credit cards include automatic travel protections when you use your card to purchase travel. I've separately compared these protections for ultra premium cards, here: Ultra-Premium Credit Card Travel Insurance. In this post, I compare protections provided by each of Chase's Ultimate Rewards cards including the Sapphire Reserve, Ink Business Preferred, Sapphire Preferred, and more. The following chart summarizes travel insurance provided automatically by each Ultimate Rewards card. Cells in green indicate best in class…
Tag Archives for Ink.
Chase's new 50K offer and their evolving Ultimate Rewards lineup
Chase released a new business credit card in May 2018: Ink Business Unlimited. Like the Chase Freedom card, the Ink Business Unlimited is advertised as a cash back card, but it really earns Ultimate Rewards points: 1.5 points per dollar for all spend. This is especially exciting for thos under 5/24. Just like the Ink Business Cash card, the Ink Business Unlimited offers a welcome bonus of $500 (50,000 Ultimate Rewards points) after $3K spend…
(EXPIRED) $10 off $100 Whole Foods Gift Card
Gyft is offering $10 off $100 on Whole Foods Market Gift Cards with promo code EASTER18. The Deal Get $10 off a $100 Whole Foods Gift Card with promo code EASTER18 Direct link to this promotion Key Details Expires 4/1/18 at 11:59pm PT or when capacity runs out Can be used up to 3 times per household while supplies last. Quick Thoughts If you shop at Whole Foods, it's a good deal to be able to get $10 off on groceries. Additionally,…
Newbie's new credit card plan, and initial results
A bit over a week ago I published "A credit card plan for a well informed newbie." There I detailed a plan for this retiree to quickly rack up huge numbers of points through credit card signups. Readers weighed in with helpful suggestions, and I modified my recommendations. I wrote: Thanks everyone. Based on your input, I'll recommend these changes to Ben: 1. Sign up for Ink Biz Pref and Ink Cash same day in…
Chase Ink Business Preferred Live Application Link Available, But No Landing Page or Bonus Mentioned
A live application link has surfaced for the Ink Business Preferred card.
Chase To Launch New Ink Business Preferred Card with 80K Bonus
Chase will be launching a new Ink business credit card this week which will have an 80K sign-up bonus and earn 3X for travel and more.
Chase Ink Cash Bonus Increased to 30K: Refer Your Friends Too
Chase is offering a 30K bonus on their Ink Cash card if you apply via a current cardholders referral link or in-branch.
Targeted Chase Ink Cash 50K Bonus Offer
Details of a new Chase Ink Cash 50K bonus offer.


text:
Otherwise, you will remain revoked forever. Our office is very familiar with all the requirements needed to clear the Illinois hold. You must answer at least 70% 42 questions correctly on the online test in order to pass. In some states, the information on this website may be considered a lawyer referral service. The attorney listings on this site are paid attorney advertising. The new registration form must be accompanied by applicable titling and registration fees.
How to Obtain Your Illinois Driving Records In Person You must apply for your driving record abstract at any local Driver Service facility within Illinois. For more detail, please read on. If you do not have a copy of those documents our office can order all of them from the Secretary of State archives. Military honor plates Illinois offers a wide variety of distinguished military honor license plates commemorating the different military branches, service medals, specific campaigns, and individual battles. We work closely with the treatment provider to ensure success in clearing the hold. Driver's License Fees The following is a summary of commonly requested information regarding driver's license fees.
You can get all these services by visiting the or you can save time and money by getting online services from their online platform. Remove the Hold from Illinois and get your driving privileges back! In addition, you must have had two years of such experience, and meet certain other criteria, such as a lack of specific types of motor vehicle offenses. It may be a Class D initial license or an initial Temporary Visitor Driver's License. We address any issues with your evaluator and verify they are fully resolved prior to submitting the Out of State We will let you know if we can help you obtain a successful outcome and make sure all the requirements by the Secretary of State are followed. This depends on your driving history, past treatment completion and other factors.
Thousands of Illinois drivers forgot to do something before the end of the year, and now it's going to cost them. Fill out the Driver Abstract Request Form 3. You will have three chances to pass the test within the year from the date on which you pay the application fee for an instruction permit or driver's license. If you do it yourself or use an inexperienced lawyer, you will likely be denied and cause serious problems with any future petitions. While the myriad rules and regulations enforced by the apply to drivers of all ages and stages, the state imposes some special requirements and restrictions on older drivers. Those ages 81 through 86 must renew their licenses every two years. Skip the repair shop, our top-rated mechanics come to you.
Armed Forces on active duty outside of Illinois, along with their spouses and children, may drive with an expired Illinois drivers license for up to 120 days upon their return to the state. Senior drivers who are deaf and hard of hearing can call 888 261-5280 for queries. If your license is expired less than a year ago you won't have to take the test again but if it's been more than a year you will need to take the test again. Having incomplete or inaccurate documentation will result in the denial of your petition. Many times a renewal can be made by mail.
There are in-person or via email after access to online driving records website. At first glance the questions may not seem too complicated, but the wrong answer can result in a denial and put the driver in a much worse situation for future petitions. This receipt is valid for 30 days after your previous registration's expiration date. Also, it is important to understand information such as what you need to renew a drivers license and where to renew so that you can be prepared ahead of time. Also, the following information is required: Whether the car is used or new, in case it is used, it must be specified if it is rebuilt or not Specify the title such as registration only, title transfer or corrected title. If deemed necessary, drivers will be required to submit a medical form, indicating their ability to drive safely. Road tests hours may change depending on the amount of customers are scheduled.
Without a hearing you will be unable to drive forever. The renewals can also be done in person at a Secretary of State facility or currency exchange. Certificates are available free of charge and will be mailed to your out-of-state address once requested. We have just taken the time to consolidate it and make the process more simple. There is a beginning and ending date which is determined by the Secretary of State.
You have 2 options to continue with this process. To get your vehicle tested, with your emissions inspection notice. The most common of these conditions is a poor vision, but others which may be age-related include cognitive skills like memory, coordination and flexibility. Illinois drivers who are younger than 74 years of age can opt for the Safe Driver Renewal. The Secretary of State is very particular about the information this documentation must include and frequently rejects submitted documents.


text:
The SolusVM Panel
A 1–stop formula for handling your OpenVZ Linux VPS Package
Each OpenVZ Linux VPS Package web server comes prepared for you to use. At sign–up, you will be able to opt for your Linux OS version (Debian, CentOS or Ubuntu) and you will even receive your very own copy of the SolusVM Virtual Manager – a powerful interface, which permits you to reboot your server at any moment and offers all–inclusive resource use stats.
OpenVZ Linux VPS Package well–prepared for all kinds of jobs
Our OpenVZ Linux VPS Package packs are supplied with all the numerous characteristics and tools you'll need to administer your multi–media websites and apps from just a single place. Every single OpenVZ Linux VPS Package deal offers a range of OS's, SSD space, root/administrator access and regular offsite file backups. You will get secured CPU and RAM allowances for speedier speeds. Also, you'll have a free Web Site Control Panel as a fantastic bonus.
A Free Control Panel
The most helpful way to organize your OpenVZ Linux VPS Package
Your OpenVZ Linux VPS Package includes an assortment of Operating Systems and a 100% free Web Site Control Panel, so that you could start working on your Internet sites right after the registration procedure has been executed. The Control Panel has been developed by our staff of professional web developers and features a drag'n'drop File Manager, thorough reports and a full–featured Domain Name Manager with boundless domain name hosting options.
Data Center Options
A choice of data centers for your OpenVZ Linux VPS Packages
The nearer your web pages are to your readers, the speedier they will be fully–loaded in their Internet browsers. We provide you a range of Data Center Facilities for your OpenVZ Linux VPS Packages. If you are focusing on visitors mainly from the US, you need to go for the USA datacenter in Chicago, IL. If your webpages are mainly intended for visitors from Africa or Europe, then you'd better pick out the United Kingdom datacenter facility in the vicinity of London. In case you want to aim at users in Asia or Australia, then you could not go wrong with the Australian datacenter at the heart of Sydney.
SSD–Based VPS Hosting Services
Improve your web site's overall performance with our SSD–built VPSs
Each of the OpenVZ Linux VPS Packages available from 1 2 3 Free domain .com comes built with SSDs as opposed to common HDDs. Obtaining solid–state disks on your VPS can be a wonderful convenience for your sites. SSDs offer much better read/write data transfer rates and also allow for a lot faster file access. This in essence implies that everything on your web server will job more quickly, including all your websites and web applications.
- US Data Center
US Data Center
Steadfast, Chicago, IL
- UK Data Center
UK Data Center
Maidenhead, Berkshire, UK
- AU Data Center
AU Data Center
Amaze, Sydney, Australia
- BG Data Center
BG Data Center
Telepoint, Sofia, Bulgaria
- Finland Data Center
Finland Data Center
Ficolo/Pori, Finland


text:
Date: 16-Mar-2020
Location: Adelaide, SA, AU
Company: Broadspectrum
The Broadspectrum Village Services team provides comprehensive Village management services including but not limited to facilities maintenance, land management, asset management, domestic services, administration, security, wellbeing and catering.
We are currently accepting Expressions of Interest from Housekeepers, to join our operations team based in South Australia
Local applicants are encouraged to apply FIFO or DIDO from Woomera, Port Augusta or Adelaide (depending on your location). The role will be 2 weeks on 1 week or 2 weeks on, 2 weeks off.
About the Role:
Reporting to the Camp Manager, Housekeepers are responsible for providing professional catering and housekeeping operations.
In the camp you will generally be working autonomously doing 10-12 hours shifts, you will be responsible for the entire cleaning of bedrooms and bathrooms, full laundry cycle, general cleaning and housekeeping duties in the camp.
What's required for the Role:
- Previous commercial cleaning experience
- Strong time management skills
- An open manual Drivers Licence (Car or Higher)
- Current First Aid and CPR certificate (this is not essential on application)
- RSA Certificate (preferred but not essential)
What do Easternwell Offer in Return?
- Competitive rates
- Long term contracts
- Exceptional safety records, standards and practices
- Access to employee benefits
- Opportunities for advancement of your career
- A supportive and family orientated team
Apply Now:
If you believe that you meet the above criteria, have the required qualities and want to work for a company who values its employees, please click the 'apply' button now!
We acknowledge the importance of ours people's diverse experiences, talents and culture that they bring to work with them each day. Embracing Diversity and Creating Inclusion are key components of our Talent Management Strategy. The creation of a Diverse and Inclusive workforce is central to our ability to unlock potential and enhance our success, creating a high-performance business.


text:
|Pancreatic Neoplasms:
|Articles by Thierry Conroy
Thu Mar 19 04:51:09 2020
|Between 2010 and 2020, T. Conroy wrote the following 26 articles about Pancreatic Neoplasms.
|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: firstname.lastname@example.com. ·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.
|Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials). 2014
Bonnetain, Franck / Bonsing, Bert / Conroy, Thierry / Dousseau, Adelaide / Glimelius, Bengt / Haustermans, Karin / Lacaine, François / Van Laethem, Jean Luc / Aparicio, Thomas / Aust, Daniela / Bassi, Claudio / Berger, Virginie / Chamorey, Emmanuel / Chibaudel, Benoist / Dahan, Laeticia / De Gramont, Aimery / Delpero, Jean Robert / Dervenis, Christos / Ducreux, Michel / Gal, Jocelyn / Gerber, Erich / Ghaneh, Paula / Hammel, Pascal / Hendlisz, Alain / Jooste, Valérie / Labianca, Roberto / Latouche, Aurelien / Lutz, Manfred / Macarulla, Teresa / Malka, David / Mauer, Muriel / Mitry, Emmanuel / Neoptolemos, John / Pessaux, Patrick / Sauvanet, Alain / Tabernero, Josep / Taieb, Julien / van Tienhoven, Geertjan / Gourgou-Bourgade, Sophie / Bellera, Carine / Mathoulin-Pélissier, Simone / Collette, Laurence. ·Methodology and Quality of Life Unit in Cancer, EA 3181, University Hospital of Besançon and CTD-INCa Gercor, UNICNCER GERICO, Besançon, France. Electronic address: firstname.lastname@example.com. · Leiden University Medical Center, Leiden, Netherlands. · Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France. · Bordeaux Segalen University & CHRU, Bordeaux, France. · Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden. · Department of Radiation Oncology, Leuven, Belgium. · Digestive Surgical Department, Tenon hospital, Paris, France. · Gastro Intestinal Cancer Unit Erasme Hospital Brussels, Belgium. · Gastroenterology Department, Avicenne Hospital, Paris 13, Bobigny, France. · Institute for Pathology, University Hospital Carl-Gustav-Carus, Dresden, Germany. · Surgical and Gastroenterological Department, Endocrine and Pancreatic Unit, Hospital of 'G.B.Rossi', University of Verona, Italy. · Institut de Cancérologie de l'Ouest - Centre Paul Papin Centre de Lutte Contre le Cancer (CLCC), Angers, France. · Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Oncology Department, Hôpital Saint-Antoine & CTD-INCa GERCOR, Assistance Publique des Hôpitaux de Paris, UPMC Paris VI, Paris, France. · Gastroenterology Department, Hopital la Timone, Assitance publique des Hopitaux de Marseille, Marseille, France. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Department of Surgery, Agia Olga Hospital, Athens, Greece. · Department of Gastroenterology, Institut Gustave Roussy, Villejuif, France. · Biostatistician, Biostatistics Unit, Centre Antoine Lacassagne, Nice, France. · Department of Radiotherapy, Institut fuer Radioonkologie, Vienna, Austria. · Department of Surgical Oncology, Royal Liverpool Hospital, United Kingdom. · Department of Gastroenterology, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Digestive Oncology and Gastro-enterology Department, Jules Bordet Institute, Brussels, Belgium. · Digestive Cancer Registry, INSERM U866, Dijon, France. · Medical Oncology Unit, Ospedali Riuniti di Bergamo, Bergame, Italy. · Inserm, Centre for Research in Epidemiology and Population Health, U1018, Biostatistics Team, Villejuif, France. · Gastroenterology Department, Caritas Hospital, Saarbrücken, Germany. · Department of the Gastrointestinal Tumors and Phase I Unit, Vall d'Hebron University Hospital, Barcelona, Spain. · Statistics Department, EORTC, Brussels, Belgium. · Department of Medical Oncology, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France. · Division of Surgery and Oncology at the University of Liverpool and Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Digestive Surgery, Universitu Hospital Strasbourg, France. · Department of Hepato-pancreatic and Biliary Surgery, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France. · Department of Hepato-gastroenterology and Digestive Oncology, Georges Pompidou European hospital, Paris, France. · Department of Radiation Oncology, Academisch Medisch Centrum, Amsterdam, The Netherlands. · Institut Du Cancer de Montpellier, Comprehensive Cancer Centre, and Data Center for Cancer Clinical Trials, CTD-INCa, Montpellier, France. · Clinical and Epidemiological Research Unit, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France; Data Center for Cancer Clinical Trials, CTD-INCa, Bordeaux, France; INSERM, Centre d'Investigation Clinique - Épidémiologie Clinique CIC-EC 7, F-33000 Bordeaux, France. ·Eur J Cancer · Pubmed #25256896.
ABSTRACT: BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.
|New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. 2012
Van Laethem, J-L / Verslype, C / Iovanna, J L / Michl, P / Conroy, T / Louvet, C / Hammel, P / Mitry, E / Ducreux, M / Maraculla, T / Uhl, W / Van Tienhoven, G / Bachet, J B / Maréchal, R / Hendlisz, A / Bali, M / Demetter, P / Ulrich, F / Aust, D / Luttges, J / Peeters, M / Mauer, M / Roth, A / Neoptolemos, J P / Lutz, M / Anonymous1151075. ·Gastrointestinal Cancer Unit, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. firstname.lastname@example.com ·Ann Oncol · Pubmed #21810728.
ABSTRACT: Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.
|Primary Thromboprophylaxis in Pancreatic Cancer Patients: Why Clinical Practice Guidelines Should Be Implemented. 2020
Farge, Dominique / Bournet, Barbara / Conroy, Thierry / Vicaut, Eric / Rak, Janusz / Zogoulous, George / Barkun, Jefferey / Ouaissi, Mehdi / Buscail, Louis / Frere, Corinne. ·Institut Universitaire d'Hématologie, Université de Paris, EA 3518, F-75010 Paris, France. · Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital, Internal Medicine, Autoimmune and Vascular Disease Unit, F-75010 Paris, France. · Department of Medicine, McGill University, Montreal, Québec, QC H4A 3J1, Canada. · University of Toulouse, F-31059 Toulouse, France. · CHU de Toulouse, Department of Gastroenterology and Pancreatology, F-31059 Toulouse, France. · Institut de Cancérologie de Lorraine, Department of Medical Oncology, Université de Lorraine, APEMAC, EA4360, F-54519 Vandoeuvre-lès-Nancy, France. · Department of Biostatistics, Université de Paris, F-75010 Paris, France. · Assistance Publique Hôpitaux de Paris, Department of Biostatistics, Fernand Widal Hospital, F-75010 Paris, France. · McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, QC H4A 3J1, Canada. · Department of Digestive, Oncological, Endocrine, and Hepatic Surgery, and Hepatic Transplantation, Trousseau Hospital, CHRU Trousseau, F-37170 Chambray-les-Tours, France. · Institute of Cardiometabolism and Nutrition, Sorbonne Université, INSERM UMRS_1166, GRC 27 GRECO, F-75013 Paris, France. · Assistance Publique Hôpitaux de Paris, Department of Haematology, Pitié-Salpêtrière Hospital, F-75013 Paris, France. ·Cancers (Basel) · Pubmed #32155940.
ABSTRACT: Exocrine pancreatic ductal adenocarcinoma, simply referred to as pancreatic cancer (PC) has the worst prognosis of any malignancy. Despite recent advances in the use of adjuvant chemotherapy in PC, the prognosis remains poor, with fewer than 8% of patients being alive at 5 years after diagnosis. The prevalence of PC has steadily increased over the past decades, and it is projected to become the second-leading cause of cancer-related death by 2030. In this context, optimizing and integrating supportive care is important to improve quality of life and survival. Venous thromboembolism (VTE) is a common but preventable complication in PC patients. VTE occurs in one out of five PC patients and is associated with significantly reduced progression-free survival and overall survival. The appropriate use of primary thromboprophylaxis can drastically and safely reduce the rates of VTE in PC patients as shown from subgroup analysis of non-PC targeted placebo-controlled randomized trials of cancer patients and from two dedicated controlled randomized trials in locally advanced PC patients receiving chemotherapy. Therefore, primary thromboprophylaxis with a Grade 1B evidence level is recommended in locally advanced PC patients receiving chemotherapy by the International Initiative on Cancer and Thrombosis clinical practice guidelines since 2013. However, its use and potential significant clinical benefit continues to be underrecognized worldwide. This narrative review aims to summarize the main recent advances in the field including on the use of individualized risk assessment models to stratify the risk of VTE in each patient with individual available treatment options.
|An update on treatment options for pancreatic adenocarcinoma. 2019
Lambert, Aurélien / Schwarz, Lilian / Borbath, Ivan / Henry, Aline / Van Laethem, Jean-Luc / Malka, David / Ducreux, Michel / Conroy, Thierry. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Université de Lorraine, Nancy, France. · Department of Digestive Surgery, Rouen University Hospital and Université de Rouen Normandie, France. · Department of Gastroenterology and Digestive Oncology, Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium. · Department of Supportive Care in Oncology, Institut de Cancérologie de Lorraine, Nancy, France. · Department of Gastroenterology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Belgium. · Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. · Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, 50519 Vandoeuvre-lès-Nancy CEDEX, France. ·Ther Adv Med Oncol · Pubmed #31598142.
ABSTRACT: Pancreatic cancer is one of the most lethal solid organ tumors. Due to the rising incidence, late diagnosis, and limited treatment options, it is expected to be the second leading cause of cancer deaths in high income countries in the next decade. The multidisciplinary treatment of this disease depends on the stage of cancer at diagnosis (resectable, borderline, locally advanced, and metastatic disease), and combines surgery, chemotherapy, chemoradiotherapy, and supportive care. The landscape of multidisciplinary pancreatic cancer treatment is changing rapidly, especially in locally advanced disease, and the number of treatment options in metastatic disease, including personalized medicine, innovative targets, immunotherapy, therapeutic vaccines, adoptive T-cell transfer, or stemness inhibitors, will probably expand in the near future. This review summarizes the current literature and provides an overview of how new therapies or new therapeutic strategies (neoadjuvant therapies, conversion surgery) will guide multidisciplinary disease management, future clinical trials, and, hopefully, will increase overall survival.
|Systemic treatment of pancreatic cancer revisited. 2019
Ducreux, Michel / Seufferlein, Thomas / Van Laethem, Jean-Luc / Laurent-Puig, Pierre / Smolenschi, Cristina / Malka, David / Boige, Valérie / Hollebecque, Antoine / Conroy, Thierry. ·Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, Université Paris Saclay, France. Electronic address: email@example.com. · Department of Internal Medicine I, University of Ulm, Ulm, Germany. · Department of Gastroenterology and Digestive oncology, Erasme University Hospital, Université Libre de Bruxelles, Bruxelles, Belgium. · Assistance Publique-Hôpitaux de Paris, Department of Biology, European Georges Pompidou Hospital, Paris, France. · Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, France. · Département de Médecine Oncologique, Gustave Roussy Cancer Center Grand Paris, France; Département d'Innovation Thérapeutique, Gustave Roussy Cancer Center Grand Paris, France. · Département d'oncologie médicale, Institut de Cancérologie de Lorraine, Université de Lorraine, Nancy, France. ·Semin Oncol · Pubmed #30638624.
ABSTRACT: Pancreatic cancer is considered to be one of the most aggressive cancers. For unknown reasons, the incidence of pancreatic cancer is slowly rising and so too are mortality rates. Over 75% of patients are diagnosed with locally advanced disease or with metastases; and more than 95% of patients have metastases at diagnosis or will develop metastases during their follow-up. Despite recent improvements in the therapy of pancreatic cancer, initially with demonstration of the activity of the FOLFIRINOX regimen and subsequently the approval of nab-paclitaxel in combination with gemcitabine, prognosis remains poor and the 5-year survival rate is less than 5%. To date, neither personalized medicine nor immunotherapy, the 2 recent revolutions of cancer treatment, have delivered major positive results in the treatment of pancreatic cancer; and it is especially clear that immune checkpoint inhibitors will not become a major tool in the treatment of pancreatic cancer. There are many ongoing studies, including those exploring combinations of chemotherapy with immunotherapy. Vaccines or T cells modified with a chimeric antigen receptor (CAR-T cells) could also play a role in the treatment of cancer in the future. The aim of this review is to discuss recent improvements in standard of care, major obstacles to overcome, recent results of new treatment combinations, and the most interesting innovative approaches.
|Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC). 2018
Neuzillet, Cindy / Gaujoux, Sébastien / Williet, Nicolas / Bachet, Jean-Baptiste / Bauguion, Lucile / Colson Durand, Laurianne / Conroy, Thierry / Dahan, Laetitia / Gilabert, Marine / Huguet, Florence / Marthey, Lysiane / Meilleroux, Julie / de Mestier, Louis / Napoléon, Bertrand / Portales, Fabienne / Sa Cunha, Antonio / Schwarz, Lilian / Taieb, Julien / Chibaudel, Benoist / Bouché, Olivier / Hammel, Pascal / Anonymous6240961 / Anonymous6250961 / Anonymous6260961 / Anonymous6270961 / Anonymous6280961 / Anonymous6290961 / Anonymous6300961 / Anonymous6310961 / Anonymous6320961 / Anonymous6330961. ·Department of Medical Oncology, Curie Institute, Versailles Saint-Quentin University (UVSQ), Saint-Cloud, France. Electronic address: firstname.lastname@example.com. · Department of Digestive, Hepato-Biliary and Pancreatic Surgery, Cochin Hospital, AP-HP, Paris Descartes Faculty of Medicine, Paris Descartes University, Sorbonne Paris Cité, Paris, France. · Hepato-Gastroenterology Department, University Hospital of Saint-Etienne, Saint Priest en Jarez, France. · Hepato-Gastroenterology Department, Pitié Salpétrière University Hospital, AP-HP, Paris Cedex 13, France. · Hepato-Gastroenterology Department, Departmental Hospital Center, La Roche sur Yon, France. · Department of Radiotherapy, Henri Mondor Hospital, AP-HP, Université Paris Est Creteil, Créteil, France. · Department of Medical Oncology, Lorraine Institute of Oncology and Lorraine University, Vandoeuvre-lès-Nancy Cedex, France. · Digestive Oncology Department, "DACCORD" (Digestif, Anatomie pathologique, Chirurgie, CISIH, Oncologie, Radiothérapie, Dermatologie) pole, CHU Timone, Marseille Cedex 05, France. · Paoli Calmettes Institute, Department of Medical Oncology and Cancer Research Center of Marseille (CRCM), INSERM U1068 Stress Cell, Aix-Marseille University, Marseille, France. · Department of Oncology and Radiotherapy, Tenon Hospital, East Paris University Hospitals, AP-HP, Paris Sorbonne University, Paris, France. · Gastroenterology Department, Béclère Hospital, AP-HP, Clamart, France. · Pathology Department, Toulouse University Hospital, Toulouse, France. · Department of Gastroenterology-Pancreatology, Beaujon Hospital, APHP, Paris 7 University, Clichy, France. · Jean Mermoz Private Hospital, Ramsay Générale de Santé, Lyon, France. · Digestive Oncology Department, Regional Institute of Cancer, Montpellier, France. · INSERM UMR 935, Paul Brousse Hospital, Hepatobiliary Center, AP-HP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. · Department of Digestive Surgery, Hôpital Charles Nicolle, Rouen University Hospital, Rouen, France and Genomic and Personalized Medicine in Cancer and Neurological Disorders, UMR 1245 INSERM, Rouen University, France. · Hepato-Gastroenterology and Digestive Oncology Department, Georges Pompidou European Hospital, AP-HP, Paris, France. · Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France. · Hepato-Gastroenterology and Digestive Oncology Department, Robert Debré University Hospital, Avenue Général Koenig, 51092 Reims Cedex, France. · Department of Digestive Oncology, Beaujon University Hospital (AP-HP), Paris VII Diderot University, Clichy-la-Garenne, France. Electronic address: firstname.lastname@example.com. ·Dig Liver Dis · Pubmed #30219670.
ABSTRACT: BACKGROUND: This document is a summary of the French intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018. DESIGN: This collaborative work was produced under the auspices of all French medical and surgical societies involved in the management of PA. It is based on the previous guidelines, recent literature review and expert opinions. Recommendations were graded in three categories, according to the level of evidence. RESULTS: Over the last seven years, significant changes in PA management have been implemented in clinical practice. Imaging/staging: diffusion magnetic resonance imaging is useful before surgery to rule out small liver metastases. SURGERY: centralization of pancreatic surgery in expert centers is associated with a decreased postoperative mortality. Adjuvant chemotherapy: modified FOLFIRINOX in fit patients, or gemcitabine, or 5-FU, or gemcitabine plus capecitabine, to be discussed on a case-by-case basis. Locally advanced PA: no survival benefit of chemoradiotherapy. Metastatic PA: FOLFIRINOX and gemcitabine plus nab-paclitaxel combination are first-line standards in fit patients; second-line with 5FU/nal-IRI or 5FU/oxaliplatin combination after first-line gemcitabine. CONCLUSION: Guidelines for management of PA are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research. However, as each individual case is particular, they cannot substitute to multidisciplinary tumor board discussion.
|Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions. 2017
Lambert, Aurélien / Gavoille, Céline / Conroy, Thierry. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France. · Department of Medical Oncology and Université de Lorraine, Institut de Cancérologie de Lorraine, 6 avenue de Bourgogne, CS 30511, 54511 Vandœuvre-lès-Nancy, France. ·Therap Adv Gastroenterol · Pubmed #28835777.
ABSTRACT: Pancreatic cancer (PC) incidence rates are rapidly increasing in developed countries, with half the patients being metastatic at diagnosis. For decades, fluorouracil, then gemcitabine regimens were the preferred palliative first-line options for fit patients with metastatic PC. FOLFIRINOX (a combination of bolus and infusional fluorouracil, leucovorin, irinotecan and oxaliplatin) was introduced to clinical practice in 2010 due to the results of the phase II/III trial (PRODIGE 4/ACCORD 11) comparing FOLFIRINOX with single-agent gemcitabine as first-line treatment for patients with MPC. Median overall survival, progression-free survival, and objective response rate were superior with FOLFIRINOX over gemcitabine and there was prolonged time to definitive deterioration in quality of life. Although FOLFIRINOX was also associated with increased toxicity, mainly febrile neutropenia and diarrhea, there has been rapid uptake of this regimen. This review closely examines optimal management and prevention of toxicities, international recommendations for first-line treatment, and use of modified FOLFIRINOX protocols. In this review, we also look at the potential benefit of FOLFIRINOX in selected groups of patients: second-line therapy, adjuvant chemotherapy, induction therapy in patients with borderline resectable and locally advanced PC. Robust validation of the FOLFIRINOX regimen in these settings requires confirmation in further randomized trials.
|FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. 2016
Suker, Mustafa / Beumer, Berend R / Sadot, Eran / Marthey, Lysiane / Faris, Jason E / Mellon, Eric A / El-Rayes, Bassel F / Wang-Gillam, Andrea / Lacy, Jill / Hosein, Peter J / Moorcraft, Sing Yu / Conroy, Thierry / Hohla, Florian / Allen, Peter / Taieb, Julien / Hong, Theodore S / Shridhar, Ravi / Chau, Ian / van Eijck, Casper H / Koerkamp, Bas Groot. ·Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Hepatogastroenterology, Antoine Beclère Hospital, Assistance publique-Hôpitaux de Paris, Paris Sud University, Clamart, France. · Department of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. · Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Medicine, Division of Medical Oncology, University of Kentucky-Markey Cancer Center, Lexington, KY, USA. · Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Hematology, Medical Oncology, Hemostasis, Rheumatology and Infectious Diseases, Paracelsus Medical University of Salzburg, Salzburg, Austria. · Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Sorbonne Paris Cité, Paris Descartes University, Cancer Research Personalized Medicine (CARPEM), Paris, France. · Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. Electronic address: email@example.com. ·Lancet Oncol · Pubmed #27160474.
ABSTRACT: BACKGROUND: 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. METHODS: We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. FINDINGS: We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%). INTERPRETATION: Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. FUNDING: None.
|Current standards and new innovative approaches for treatment of pancreatic cancer. 2016
Conroy, Thierry / Bachet, Jean-Baptiste / Ayav, Ahmet / Huguet, Florence / Lambert, Aurélien / Caramella, Caroline / Maréchal, Raphaël / Van Laethem, Jean-Luc / Ducreux, Michel. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, 6 avenue de Bourgogne, CS 30519, 54519, Vandoeuvre-lès-Nancy, France. Electronic address: email@example.com. · Department of Hepato-Gastroenterology, Pitié-Salpétrière University Hospital, 47-83 boulevard de l'hôpital, 75651, Paris Cedex 13, France. · Department of Surgery, Nancy University Hospital Lorraine and Lorraine University, rue du Morvan, 54511, Vandoeuvre-lès Nancy, France. · Department of Radiation Therapy, Tenon Hospital, Paris Est University Hospitals, 4 rue de la Chine, 75020, Paris, France. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, 6 avenue de Bourgogne, CS 30519, 54519, Vandoeuvre-lès-Nancy, France. · Gustave Roussy Cancer Campus Grand Paris, 114 rue Edouard-Vaillant, 94805, Villejuif Cedex, France. · Department of Gastroenterology, Erasme University Hospital-ULB-Brussels, Lennikstreet 808, 1070, Brussels, Belgium. ·Eur J Cancer · Pubmed #26851397.
ABSTRACT: Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies.
|The role of the FOLFIRINOX regimen for advanced pancreatic cancer. 2013
Conroy, Thierry / Gavoille, Céline / Samalin, Emmanuelle / Ychou, Marc / Ducreux, Michel. ·EA 4360 and Department of Medical Oncology, Centre Alexis Vautrin, Université de Lorraine, Vandoeuvre-lès-Nancy, France. firstname.lastname@example.com ·Curr Oncol Rep · Pubmed #23341367.
ABSTRACT: In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) emerged as a new option in patients with metastatic pancreatic cancer and a good performance status. However, at that time, some doubts were raised regarding safety issues. Similarly, no data on FOLFIRINOX were published in patients with unresectable/locally advanced or borderline resectable pancreatic cancer. This article presents the available experience with FOLFIRINOX outside clinical trials in metastatic and locally advanced pancreatic cancer patients. The safety of the regimen in patients with biliary stents and in previously treated patients is also described. FOLFIRINOX usage in clinical practice, including modification of the regimen (omission of bolus 5-fluorouracil; FOLFOXIRI regimen), is also presented. These data suggest that a phase III randomized study is warranted to further explore the role of FOLFIRINOX in locally advanced pancreatic cancer.
|[Chemotherapy of metastatic pancreatic adenocarcinoma: challenges and encouraging results]. 2011
Conroy, Thierry / Mitry, Emmanuel. ·Centre Alexis-Vautrin, département d'oncologie médicale, Vandœuvre-lès-Nancy, France. email@example.com ·Bull Cancer · Pubmed #22133915.
ABSTRACT: The outcome for patients with metastatic pancreatic ductal adenocarcinoma is dismal. In this article, we will review current first-line treatments for metastatic pancreatic adenocarcinoma focusing on phase III randomized studies. Single-agent gemcitabine, the reference treatment since 1995, offers only slight benefit. Numerous trials using gemcitabine in combination with different cytotoxic agents have resulted in no major improvement compared to gemcitabine alone. Only the gemcitabine-erlotinib combination has shown a small, but statistically improvement in survival. In selected patients with good performance status ECOG 0-1, no cardiac ischemia and almost normal bilirubin level, the Folfirinox regimen, when compared to gemcitabine as single agent, was associated with more toxicities, but also with significant increased survival and delay in the degradation of quality of life. So, Folfirinox is a new more toxic and more efficient regimen that may be considered in patients with good performance status.
|Metastatic pancreatic cancer: old drugs, new paradigms. 2011
Conroy, Thierry / Gavoille, Céline / Adenis, Antoine. ·Department of Medical Oncology, Centre Alexis Vautrin, Nancy University, Vandoeuvre-lès-Nancy, France. email@example.com ·Curr Opin Oncol · Pubmed #21505335.
ABSTRACT: PURPOSE OF REVIEW: Metastatic pancreatic ductal adenocarcinoma has a grim prognosis and gemcitabine has been the reference treatment for 15 years. In this article, we will review current first-line treatments for metastatic pancreatic adenocarcinoma focusing on randomized studies. RECENT FINDINGS: Among the numerous randomized phase III studies comparing gemcitabine as single agent to gemcitabine combined to a new agent, only the gemcitabine-erlotinib combination has shown a small, but statistical improvement in survival. A trend to better survival was also observed with a gemcitabine-capecitabine regimen. The use of low-weight heparin may be of value to reduce venous thromboembolic events. In selected patients with good performance status ECOG 0-1, the Folfirinox regimen, when compared with gemcitabine, was associated with more toxicities and significantly increased median survival from 6.8 to 11.1 months. SUMMARY: Gemcitabine (with or without erlotinib or capecitabine) is still the reference treatment in patients with ECOG performance status 2. Folfirinox is a new more toxic and more efficient regimen that may be considered in patients with good performance status.
|Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2015
Ducreux, M / Cuhna, A Sa / Caramella, C / Hollebecque, A / Burtin, P / Goéré, D / Seufferlein, T / Haustermans, K / Van Laethem, J L / Conroy, T / Arnold, D / Anonymous4311075. ·Département de médecine, Gustave Roussy, Villejuif Faculté de Médecine, Université Paris Sud, le Kremlin Bicêtre. · Faculté de Médecine, Université Paris Sud, le Kremlin Bicêtre Département de Chirugie Hépato-biliaire, Hopital Paul Brousse, Villejuif. · Département d'imagerie. · Département de médecine, Gustave Roussy, Villejuif Département d'Innovation Thérapeutique. · Département de médecine, Gustave Roussy, Villejuif. · Département de Chirurgie Générale, Gustave Roussy, Villejuif, France. · Department of Internal Medicine I, Ulm University Hospital Medical Center, Ulm, Germany. · Department of Radiation Oncology, Leuven Kankerinstitute, Leuven. · Departement of Gastroenterology, Hôpital Erasme, Cliniques Universitaires de Bruxelles, Brussels, Belgium. · Département de médecine, Institut de Cancérologie de Lorraine, Vandoeuvre lés Nancy, France. · Department of Medical Oncology, Tumor Biology Center, Freiburg, Germany. ·Ann Oncol · Pubmed #26314780.
ABSTRACT: -- No abstract --
|Clinical Trial
|FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. 2018
Conroy, Thierry / Hammel, Pascal / Hebbar, Mohamed / Ben Abdelghani, Meher / Wei, Alice C / Raoul, Jean-Luc / Choné, Laurence / Francois, Eric / Artru, Pascal / Biagi, James J / Lecomte, Thierry / Assenat, Eric / Faroux, Roger / Ychou, Marc / Volet, Julien / Sauvanet, Alain / Breysacher, Gilles / Di Fiore, Frédéric / Cripps, Christine / Kavan, Petr / Texereau, Patrick / Bouhier-Leporrier, Karine / Khemissa-Akouz, Faiza / Legoux, Jean-Louis / Juzyna, Béata / Gourgou, Sophie / O'Callaghan, Christopher J / Jouffroy-Zeller, Claire / Rat, Patrick / Malka, David / Castan, Florence / Bachet, Jean-Baptiste / Anonymous971096. ·From the Institut de Cancérologie de Lorraine and Université de Lorraine (T.C.) and Centre Hospitalier Universitaire (L.C.), Nancy, Hôpital Beaujon and University Paris VII, Clichy (P.H., A.S.), Hôpital Huriez, Lille (M.H.), Centre Paul Strauss, Strasbourg (M.B.A.), Institut Paoli-Calmettes, Marseille (J.-L.R.), Centre Antoine-Lacassagne, Nice (E.F.), Hôpital Jean-Mermoz, Lyon (P.A.), Hôpital Trousseau, Tours (T.L.), Centre Hospitalier Universitaire de Saint-Eloi (E.A.) and Institut du Cancer de Montpellier-Val d'Aurelle, Université de Montpellier (M.Y., S.G., F.C.), Montpellier, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon (R.F.), Centre Hospitalier Universitaire Robert Debré, Reims (J.V.), Hôpital Louis Pasteur, Colmar (G.B.), Normandie University, Rouen University Hospital, Rouen (F.D.F.), Hôpital Layné, Mont-de-Marsan (P.T.), Centre Hospitalier Universitaire Côte de Nacre, Caen (K.B.-L.), Hôpital Saint-Jean, Perpignan (F.K.-A.), Centre Hospitalier Régional, Orléans (J.-L.L.), R&D Unicancer (B.J., C.J.-Z.) and Sorbonne Université, Hôpitaux Universitaires Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (J.-B.B.), Paris, Gustave Roussy, Université Paris-Saclay, Villejuif (D.M.), and Centre Hospitalier Universitaire, Dijon (P.R.) - all in France · and the Princess Margaret Cancer Centre, Toronto (A.C.W.), Kingston General Hospital (J.J.B.) and the Canadian Cancer Trials Group, Queen's University (C.J.O.), Kingston, ON, the Ottawa Health Research Institute, Ottawa (C.C.), and Segal Cancer Centre, Jewish General Hospital, Montreal (P.K.) - all in Canada. ·N Engl J Med · Pubmed #30575490.
ABSTRACT: BACKGROUND: Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer. METHODS: We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks. The primary end point was disease-free survival. Secondary end points included overall survival and safety. RESULTS: At a median follow-up of 33.6 months, the median disease-free survival was 21.6 months in the modified-FOLFIRINOX group and 12.8 months in the gemcitabine group (stratified hazard ratio for cancer-related event, second cancer, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.73; P<0.001). The disease-free survival rate at 3 years was 39.7% in the modified-FOLFIRINOX group and 21.4% in the gemcitabine group. The median overall survival was 54.4 months in the modified-FOLFIRINOX group and 35.0 months in the gemcitabine group (stratified hazard ratio for death, 0.64; 95% CI, 0.48 to 0.86; P=0.003). The overall survival rate at 3 years was 63.4% in the modified-FOLFIRINOX group and 48.6% in the gemcitabine group. Adverse events of grade 3 or 4 occurred in 75.9% of the patients in the modified-FOLFIRINOX group and in 52.9% of those in the gemcitabine group. One patient in the gemcitabine group died from toxic effects (interstitial pneumonitis). CONCLUSIONS: Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer, at the expense of a higher incidence of toxic effects. (Funded by R&D Unicancer and others; ClinicalTrials.gov number, NCT01526135 ; EudraCT number, 2011-002026-52 .).
|Clinical Trial
|Retrospective Analysis of CA19-9 Decrease in Patients with Metastatic Pancreatic Carcinoma Treated with FOLFIRINOX or Gemcitabine in a Randomized Phase III Study (ACCORD11/PRODIGE4). 2017
Robert, Marie / Jarlier, Marta / Gourgou, Sophie / Desseigne, Françoise / Ychou, Marc / Bouché, Olivier / Juzyna, Beata / Conroy, Thierry / Bennouna, Jaafar. ·Department of Medical Oncology, Institut de Cancérologie de l'Ouest, St. Herblain, France. ·Oncology · Pubmed #28982109.
ABSTRACT: OBJECTIVES: Carbohydrate antigen 19-9 (CA19-9) is a sensitive and specific serum marker in pancreatic cancer. Our retrospective analysis aims to evaluate CA19-9 decrease in patients with metastatic pancreatic cancer treated in ACCORD11/PRODIGE4 (FOLFIRINOX vs. gemcitabine). METHODS: A total of 342 patients were treated. CA19-9 was measured at 8 weeks (±2) in 160 patients from a total of 282 with abnormal CA19-9 values at baseline (gemcitabine arm, n = 75; FOLFIRINOX arm, n = 85). In the present study, 8-week CA19-9 decrease or greater CA19-9 decrease according to the 20 and 90% thresholds were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated in each subgroup. RESULTS: In the FOLFIRINOX arm, patients with an 8-week CA19-9 decrease or greater CA19-9 decrease ≥20% showed improved median OS, PFS, and objective response rate. In the overall study population, median OS and PFS were significantly improved in patients with an 8-week CA19-9 decrease ≥20% (vs. <20%). The 8-week CA19-9 decrease was predictive of PFS (interaction test significant according to treatment arm; p = 0.006). CONCLUSION: An 8-week CA19-9 decrease ≥20% is a prognostic factor for OS and PFS. The 8-week CA19-9 decrease (20% threshold) is predictive of PFS. It could help to evaluate the efficacy of FOLFIRINOX and gemcitabine regimens.
|Clinical Trial
|Response to FOLFIRINOX by gender in patients with metastatic pancreatic cancer: Results from the PRODIGE 4/ ACCORD 11 randomized trial. 2017
Lambert, Aurélien / Jarlier, Marta / Gourgou Bourgade, Sophie / Conroy, Thierry. ·Department of medical oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France. · Biostatistics unit, Institut régional du cancer de Montpellier, Parc Euromédecine, Montpellier, France. ·PLoS One · Pubmed #28931010.
ABSTRACT: BACKGROUND: Hohla et al. suggested that female gender could positively predict response to FOLFIRINOX in patients with advanced pancreatic cancer. In this study, we explored the response to the FOLFIRINOX regimen by gender within the trial PRODIGE4/ACCORD 11. PATIENTS AND METHODS: Data were described by gender, both in FOLFIRINOX group and in the intention-to-treat population of the trial. The relative effect of gender (females in comparison to males) on overall survival (OS) and progression-free survival was estimated by using a Cox proportional hazard model and was presented with the Hazard Ratio and their 95% confidence interval. The analysis of prognostic factors of OS included also: age (older than 65 years), ECOG performance status, primary tumor location, synchronous metastases, number of metastatic sites, hepatic metastasis, pulmonary metastases, lymph node metastases, level of Albumin and level of serum carbohydrate antigen 19-9 and three domains from the EORTC Quality of Life QLQC-30 questionnaire. RESULTS: The FOLFIRINOX group (N = 171 patients) included 106 women (62%) and 65 men. No significant differences were observed between genders regarding demographic and clinical parameters, excepted for lymph nodes metastasis (17% and 35% in women and men respectively; p = 0.012). Median OS was longer for females as compared to males in FOLFIRINOX group (13.1 versus 10.3 months respectively; HR = 0.73; 95% CI, 0.51-1.06). Similarly, median PFS was superior (7.2 versus 5.9 months; HR = 0.79; 95% CI, 0.57-1.10). Nevertheless, in both cases, the differences were not statistically significant (p = 0.10 et p = 0.169, respectively). CONCLUSIONS: In this study, the overall survival and progression-free survival rates were not significantly higher for females than for males in FOLFIRINOX group (HR = 0.73; 95% CI, 0.51-1.06 and HR = 0.79; 95% CI, 0.57-1.10 respectively). Even if the percentage of patients with lymph node metastasis is higher for males than for females, the interaction between gender and lymph node metastasis was non-significant. Our exploratory analysis did not permit to definitively conclude about a possible effect of gender on the prognosis of patients under FOLFIRINOX. This subject deserves further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00112658. KEY MESSAGE: Our analysis suggests that FOLFIRINOX, as first-line option for patients with metastatic pancreatic cancer who are younger than 76 years and who have a good performance status (ECOG 0 or 1), no cardiac ischemia and normal or nearly normal bilirubin levels, is beneficial, but not particularly in female patients.
|Clinical Trial
|Radiation plus docetaxel and cisplatin in locally advanced pancreatic carcinoma: a non-comparative randomized phase II trial. 2014
Ducreux, Michel / Giovannini, Marc / Baey, Charlotte / Llacer, Carmen / Bennouna, Jaafar / Adenis, Antoine / Peiffert, Didier / Mornex, Françoise / Abbas, Moncef / Boige, Valèrie / Pignon, Jean-Pierre / Conroy, Thierry / Cellier, Patrice / Juzyna, Beata / Viret, Frédéric. ·Gustave Roussy, Villejuif, France; Université Paris Sud, Le Kremlin Bicetre, France. Electronic address: email@example.com. · Institut Paoli Calmettes, Marseille, France. · Gustave Roussy, Villejuif, France. · Institut du Cancer Montpellier - Val d'Aurelle, Montpellier, France. · Institut de Cancérologie de l'Ouest - René Gauducheau, Nantes, France. · Centre Oscar Lambret, Lille, France. · Institut de Cancérologie de Lorraine - Alexis Vautrin, Nancy, France. · Hôpital Lyon Sud, Lyon, France. · Institut de Cancérologie de l'Ouest - Paul Papin, Angers, France. · Unicancer, Paris, France. ·Dig Liver Dis · Pubmed #25027552.
ABSTRACT: BACKGROUND: We performed a randomized, non-comparative phase II study evaluating docetaxel in combination with either daily continuous (protracted IV) 5-fluorouracil or cisplatin administered weekly, concurrent to radiotherapy in the treatment of locally advanced pancreatic carcinoma. Results of the docetaxel plus cisplatin regimen are reported. METHODS: Forty chemotherapy-naive patients with locally advanced pancreatic carcinoma were randomly assigned to receive 5-fluorouracil and docetaxel or docetaxel 20mg/m(2) and cisplatin 20mg/m(2)/week, plus concurrent radiotherapy for 6 weeks. The radiation dose to the primary tumour was 54Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate. RESULTS: 51 patients from 7 centres were included in the docetaxel-cisplatin treatment group. Six-month non-progression rate was 39% (95% confidence interval: 26-53). Median overall survival was 9.6 months (95% confidence interval: 2.4-60.7); 6 complete and 8 partial responses were obtained. Six patients survived more than 2 years after their inclusion in the trial. Grade ≥3 toxicity was reported in 63% of patients; no treatment-related death occurred. Severe toxicities were mainly anorexia (22%), vomiting (20%) and fatigue (24%). CONCLUSIONS: Despite inadequate efficacy according to the main end point, this regimen gave a satisfactory rate of objective response (27%) with tolerable toxicity.
|Clinical Trial
|Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. 2013
Gourgou-Bourgade, Sophie / Bascoul-Mollevi, Caroline / Desseigne, Françoise / Ychou, Marc / Bouché, Olivier / Guimbaud, Rosine / Bécouarn, Yves / Adenis, Antoine / Raoul, Jean-Luc / Boige, Valérie / Bérille, Jocelyne / Conroy, Thierry. ·Centre Léon Bérard, Lyon, France. ·J Clin Oncol · Pubmed #23213101.
ABSTRACT: PURPOSE: To compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Three hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m(2); irinotecan, 180 mg/m(2); leucovorin, 400 mg/m(2); and fluorouracil, 400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks. RESULTS: Improvement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain, insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration ≥ 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin. CONCLUSION: FOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables.
|Clinical Trial
|FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. 2011
Conroy, Thierry / Desseigne, Françoise / Ychou, Marc / Bouché, Olivier / Guimbaud, Rosine / Bécouarn, Yves / Adenis, Antoine / Raoul, Jean-Luc / Gourgou-Bourgade, Sophie / de la Fouchardière, Christelle / Bennouna, Jaafar / Bachet, Jean-Baptiste / Khemissa-Akouz, Faiza / Péré-Vergé, Denis / Delbaldo, Catherine / Assenat, Eric / Chauffert, Bruno / Michel, Pierre / Montoto-Grillot, Christine / Ducreux, Michel / Anonymous1530694 / Anonymous1540694. ·Nancy University and Department of Medical Oncology, Centre Alexis Vautrin, Nancy, France. firstname.lastname@example.com ·N Engl J Med · Pubmed #21561347.
ABSTRACT: BACKGROUND: Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer. METHODS: We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival. RESULTS: The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). CONCLUSIONS: As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).
|Adjuvant treatment of pancreatic cancer. 2019
Conroy, Thierry / Ducreux, Michel. ·Department of Medical Oncology, Institut de Cancérologie de Lorraine and Université de Lorraine, Nancy. · Department of Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. ·Curr Opin Oncol · Pubmed #30994497.
ABSTRACT: PURPOSE OF REVIEW: Pancreatic cancer will soon become one of the most common causes of cancer death. Early detection of pancreatic cancer remains impossible and only 20% of patients are suitable for surgery once diagnosed. Even in this specific subgroup of patients, and despite improvements in surgery, overall survival remains poor, with an 80% recurrence rate. Consequently, many attempts have been made to prevent recurrence by adding chemotherapy, radiotherapy, or both. RECENT FINDINGS: Here, we will focus on results of randomized trials evaluating the role of different postoperative treatments. Over 15 years ago, a trial demonstrated that chemoradiotherapy has a deleterious effect on survival. The same trial recommended adjuvant chemotherapy with fluorouracil as standard of care. Subsequent trials sought to identify better chemotherapy regimens. Two recently published trials evaluated the role of combination therapies for resected pancreatic cancer and demonstrated better outcomes with a gemcitabine and capecitabine combination and a fluorouracil, oxaliplatin, and irinotecan combination (FOLFIRINOX) versus gemcitabine alone. SUMMARY: Results from recent trials suggest that FOLFIRINOX should be considered standard of care for fit patients.
|Combination or single-agent chemotherapy as adjuvant treatment for pancreatic cancer? 2019
Conroy, Thierry / Van Laethem, Jean-Luc. · ·Lancet Oncol · Pubmed #30842047.
ABSTRACT: -- No abstract --
|Chemotherapy for pancreatic cancer: the rise of multidrug regimens. 2018
Malka, David / Borbath, Ivan / Conroy, Thierry. ·Gustave Roussy, Université Paris-Saclay, Département de Médecine Oncologique, Villejuif, France. Electronic address: email@example.com. · Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Service d'Hépato-Gastroentérologie, Brussels, Belgium. · Institut de Cancérologie de Lorraine and Université de Lorraine, Nancy, France. ·Lancet Gastroenterol Hepatol · Pubmed #30215353.
ABSTRACT: -- No abstract --
|An assessment of the benefit-risk balance of FOLFIRINOX in metastatic pancreatic adenocarcinoma. 2016
Péron, Julien / Roy, Pascal / Conroy, Thierry / Desseigne, Françoise / Ychou, Marc / Gourgou-Bourgade, Sophie / Stanbury, Trevor / Roche, Laurent / Ozenne, Brice / Buyse, Marc. ·CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Service de Biostatistiques, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France. · Medical Oncology Department, Centre Hospitalier Lyon-Sud, Institut de Cancérologie des Hospices Civils de Lyon-IC-HCL, 69495 Pierre-Bénite, France. · Institut de Cancérologie de Lorraine, Alexis Vautrin Center, 54500 Vandœuvre-lès-Nancy, France. · Medical Oncology Department, Centre Léon Bérard, 69373 Lyon, France. · Institut Régional du Cancer Montpellier, Val d'Aurelle, 34298 Montpellier, France. · R&D UNICANCER, 75013 Paris, France. · International Drug Development Institute (IDDI), San Francisco, CA 94109, USA. ·Oncotarget · Pubmed #27765912.
ABSTRACT: BACKGROUND: We sought to assess the benefit-risk balance of FOLFIRINOX versus gemcitabine in patients with metastatic pancreatic adenocarcinoma. METHODS: We used generalized pairwise comparisons. This statistical method permits the simultaneous analysis of several prioritized outcome measures. The first priority outcome was survival time (OS). Differences in OS that exceeded two months were considered clinically relevant. The second priority outcome was toxicity. The overall treatment effect was quantified using the net chance of a better outcome, which can be interpreted as the net probability for a random patient treated in the FOLFIRINOX group to have a better overall outcome than a random patient in the gemcitabine group. RESULTS: In this trial 342 patients received either FOLFIRINOX or gemcitabine. The net chance of a better outcome favored strongly and significantly the FOLFIRINOX group (24.7; P<.001), suggesting a favorable benefit-risk balance of FOLFIRINOX versus gemcitabine. The positive benefit-risk balance of FOLFIRINOX was observed throughout all sensitivity analyses. CONCLUSIONS: Generalized pairwise comparisons are useful to perform a quantitative assessment of the benefit-risk balance of new treatments. It provides a clinically intuitive way of comparing patients with respect to all important efficacy and toxicity outcomes. Overall the benefit-risk balance of FOLFIRINOX was strongly positive.
|Applying the Longitudinal Model from Item Response Theory to Assess Health-Related Quality of Life in the PRODIGE 4/ACCORD 11 Randomized Trial. 2016
Barbieri, Antoine / Anota, Amélie / Conroy, Thierry / Gourgou-Bourgade, Sophie / Juzyna, Beata / Bonnetain, Franck / Lavergne, Christian / Bascoul-Mollevi, Caroline. ·Biometrics Unit-CTD INCa, Institut régional du Cancer Montpellier (ICM) - Val d'Aurelle, Montpellier, France (AB, SG-B, CB-M) · Institut Montpelliérain Alexander Grothendieck, University of Montpellier, Montpellier, France (AB, CL) · National Quality of Life in Oncology Platform, France (AA, TC, FB) · Methodological and Quality of Life Unit in Oncology (EA 3181), Besançon, France (AA, FB) · Institut de Cancérologie de Lorraine, Nancy, France (TC) · Unicancer R&D, Paris, France (BJ) · Université Paul-Valéry Montpellier 3, Montpellier, France (CL) ·Med Decis Making · Pubmed #26683246.
ABSTRACT: INTRODUCTION: A new longitudinal statistical approach was compared to the classical methods currently used to analyze health-related quality-of-life (HRQoL) data. The comparison was made using data in patients with metastatic pancreatic cancer. METHODS: Three hundred forty-two patients from the PRODIGE4/ACCORD 11 study were randomly assigned to FOLFIRINOX versus gemcitabine regimens. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. The classical analysis uses a linear mixed model (LMM), considering an HRQoL score as a good representation of the true value of the HRQoL, following EORTC recommendations. In contrast, built on the item response theory (IRT), our approach considered HRQoL as a latent variable directly estimated from the raw data. For polytomous items, we extended the partial credit model to a longitudinal analysis (longitudinal partial credit model [LPCM]), thereby modeling the latent trait as a function of time and other covariates. RESULTS: Both models gave the same conclusions on 11 of 15 HRQoL dimensions. HRQoL evolution was similar between the 2 treatment arms, except for the symptoms of pain. Indeed, regarding the LPCM, pain perception was significantly less important in the FOLFIRINOX arm than in the gemcitabine arm. For most of the scales, HRQoL changes over time, and no difference was found between treatments in terms of HRQoL. DISCUSSION: The use of LMM to study the HRQoL score does not seem appropriate. It is an easy-to-use model, but the basic statistical assumptions do not check. Our IRT model may be more complex but shows the same qualities and gives similar results. It has the additional advantage of being more precise and suitable because of its direct use of raw data.


text:
With app and game limits, parents can choose to set a one-hour limit for their child to play games such as ARK: Survival Evolved, or their favourite social media app. The feature seamlessly works across devices, so once that time is spent on Xbox, the child won't be able to get around the limit on their Windows 10 PC or Android phone via Microsoft Launcher. With app and game limits, children can still use their devices for other things, like homework, without the distraction of their favourite game or app.At the end of the day, we can't blame screens, apps or games for anything related to child behaviour and activity (or inactivity), it all comes down to the parents. But options like this are incredibly helpful and should be welcomed with open arms. Find out more by clicking here.
The app and game limits feature is complimentary to the more than 20 existing family settings features that work on Xbox One and Windows 10 devices across four key categories:
Every Xbox One console and Windows 10 device comes equipped with family settings to ensure children have age-appropriate access and the right balance of technology in their lives.
- Screen time management – Limit access to the Xbox One console or Windows 10 device on school days or provide more gaming time on the weekend
- Purchase limits – Parents can approve the purchase of apps and games before they are made
- Content filters – Filter or allow games, apps and websites based on the age of each child
- Privacy – Parents can select what personal information others can see and who is permitted to engage with their children


text:
Mrs. Sallit's Biography
Greetings Borough Families! It is my pleasure to spend another year at the Borough Schools!!!
My name is Renee Sallit and this is my fourth year here in Northampton! I would love to take a moment to share a bit about myself with you :)! I am the wife of Mr. Sallit, and we are the lucky and busy parents of Xayden (10), Xyler (8), and Xella (5). We are also loving and patient owners of Prince (12 in doggy years). Mr. Sallit is in education as well---2nd grade teacher in the Allentown School District. We keep very busy with our extremely large families, wrestling tournaments, and football games :-). I was born and raised in Allentown, PA. I am an Alumni of Parkland High School, East Stroudsburg University, and Cabrini College. My family and I currently reside in Lower Macungie Township.Prior to joining the NASD family, I was a teacher/administrator in the Allentown School District, and a teacher in the Northwestern Lehigh School District prior to that My passion for children and education grew exponentially when I was in high school and I had the opportunity to participate in a Child Development Program for 4 years. I have been extremely thankful to have several experiences throughout my career to gain a wide variety of knowledge in order to serve the Borough students!My goal for the Borough schools is to make an impact on your child by building a culture throughout the building and the community where students feel safe, nurtured, and empowered to be lifelong learners. It is crucial for me to build a relationship and sense of trust with the families of our students in order for us to provide the best opportunity for student achievement.
I am looking forward to another wonderful school year for 2018-2019. Should you ever have any questions and concerns, please do not hesitate to reach out to me. I am always here for my staff, students, families, and community members.
Mrs. Renee Sallit


text:
JACKSON, MI (WILX) -- Consumers Energy said they have restored power to over 47,000 customers after powerful storms knocked out power to more than 54,000 residents and businesses.
"Favorable weather today aided our efforts to restore a large portion of customers impacted by Wednesday's damaging weather and we're going to work through the night to continue reducing the number of customers without electric service," said Consumers Energy Vice President Greg Salisbury. "We can't thank our customers enough for their patience as we push to restore power to the remaining 7,000 customers."
The company said over 54,000 customers were affected by the severe weather, which packed winds more than 50 miles per hour. A majority of customers were expected to have power restored by the end of the day Thursday.
The company said those in the hardest hit areas are expected to be restored by late Friday.
Consumers Energy said more than 280 downed wires were attributed to the weather and from customer service representatives to damage assessors and lineworkers, more than 750 Consumers Energy employees and contract personnel are engaged in the restoration effort.
Salisbury urged customers and the public to stay at least 25 feet away from downed power lines, keep children or pets away and report the issue by calling 911 and Consumers Energy at 800-477-5050.
Consumers Energy said to also keep these safety tips in mind:
• Call 2-1-1 if you are looking for help connecting to temporary shelter or other resources that offer assistance in your community. 2-1-1 is a free statewide service.
• Never use a generator in an attached garage, basement, enclosed patio or near any air intakes. Doing so could cause a generator to produce hazardous levels of carbon monoxide, an odorless, colorless and deadly gas.
• Be alert to crews working along roads. Drivers should slow down or stop and wait for oncoming traffic to clear so they safely can go past workers on roadsides.
• Consumers Energy will trim or remove trees interfering with electric restoration activities. Once safe to do so, clean-up of debris from tree trimming or removal during a storm emergency is the responsibility of individual property owners.
• In some cases, the mast which holds the electric service wires to a customer's home or business may have been damaged or torn away. Crews will reconnect the wires to a home, but only a licensed electrician can repair or replace a mast or a cable.
Customers can report an outage, check the status of an outage and get tips on what to do after a storm by clicking here.
No injuries were reported in the storms Wednesday.
The National Weather Service says a possible tornado was reported in the western Michigan city of Grand Rapids and emergency management officials in surrounding Kent County say several possible brief tornadoes were spotted on radar.
Firefighters evacuated a Grand Rapids apartment building after winds tore off the roof and damaged other nearby buildings.
Damage was reported in Lowell and Ada.
DTE Energy says about 74,000 of its customers were affected, with about 33,000 without power around midday Thursday.
Copyright 2019 WILX. All rights reserved.


text:
Christmas Capital of Texas Tickets
Grapevine's Hometown Christmas Exhibit
Tower Gallery inside the Visitor Information Center
636 S. Main St.
Relive those childhood traditions you love by strolling through vintage vignettes showcasing the charm and spirit of a classic town preparing for Christmas.
THIS EVENT HAS ENDED - We hope to see you next year!
After Christmas Trains
Board the Grapevine Vintage Railroad after Christmas to end 2019 on the right track! Enjoy the magic of the holiday season as all coaches feature beautiful Christmas decorations.
ALL TRAINS FULL - We hope to see you next year!


text:
December 15
The "Coventry Carol" is a song from the Pageant of the Shearmen and Tailors, performed in Coventry in the 15th and 16th centuries. Several monarchs, including Richard III and Henry VII, attended the Coventry plays. This song tells the story of Herod's slaughter of the innocents.
This piece is performed on piano by Mark Gionfriddo. Mark directs the Jazz Program and is Catholic Music Director at Mount Holyoke College, Liddy's alma mater. Though he does have a Steinway M in his office and always prefers to play "the real thing", he recorded his selection using his Ensoniq KS-32 weighted action synthesizer digitally interfaced to his office iMac. Mark selected a Steinway grand piano sample instrument in Logic Studio. He believes in keeping up with technology- and now plays many gigs using a synth and a MacBook Pro with Logic Studio, which not surprisingly is a lot easier on his back muscles!
Downloads: mp3 mp3 (256 kbps)
Coventry Carol
Performed by Mark Gionfriddo on piano
Words: Pageant of the Shearmen and Tailors, 15th century; attr. Robert Croo, 1534.
Music: English melody, 15th century (published 1591).
Lul-ly, lul-la, thou little tiny child,
By, by, lul-ly, lul-lay.
Lul-ly, lul-la, thou little tiny child,
By, by, lul-ly, lul-lay.
O sisters, too,
How may we do
For to preserve this day
This poor youngling
For whom we do sing,
By, by, lul-ly, lul-lay.
Herod the King,
In his raging,
Charged he hath this day
His men of might,
In his own sight,
All children young to slay.
Then woe is me,
Poor child, for thee!
And ever morn and day,
For thy parting
Neither say nor sing
By, by, lul-ly, lul-lay.
Sources and more information
- Oxford Book of Carols, 1964.
- Hymns and Carols of Christmas
- Wikipedia


text:
*** COVID-19 ATTENTION VALUED CUSTOMERS: You may be aware, much of our state and all non-essential businesses are on a Shelter-In-Place Ordinance shutting all non-essential business's up to May 1st or until further notice. Thus, our shipping operations are restricted and we may not be able to ship out any orders until we resume operations. We have no control over this situation and hope you will understand the current circumstances which we are all facing across the nation.
Our customer service team is working remotely and will be able to respond to emails and phone calls between the hours of 9am-5pm CST Monday-Friday
We appreciate your patience and thank you for being a valued member of myjewelersclub.com
14k White Gold Stud Earrings with White Hue Faceted Cubic Zirconia
This is a pair of classic stud earrings. Cubic zirconia accents are measuring 6 millimeters highlight the polished 14k white gold sections of these beauties.


text: Wicca Moon Tarot Cards & Book Set OFFER! Free Wicca Moon Mug! £24.99 Quantity: at £24.99 each Add To Basket SPECIAL OFFER - This offer includes a Wicca Moon Mug! New print run of our fabulous tarot cards just arrived. Self published Wicca Moon Tarot created by local artist. You can find reviews of our wonderful deck on youtube. You will receive the deck and accompanying 124 page book beautifully wrapped.


text:
|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|Ksenia Khailenko <xenia_khaile...@tut.by>
|Fwd: Gsoc project
|Mon, 13 Jun 2011 06:17:46 GMT
Hi there FYI, Redirecting mail from Eshan, I'll reply this letter in more details a bit later ---------- Forwarded message ---------- From: Eshan Sudharaka <email@example.com> Date: 2011/6/12 Subject: Gsoc project To: Ksenia Khailenko <email@example.com> Hy Ksenia , First of all i want to apologize since i was not able to continue my work at gsoc project since i had my job interviews as well as i was stuck with my final year project. Actually i know this is not a excuse and that is why i am sending this email in private. Some how i will promise you to complete my target work before the dead line of mid term evaluation. (nearly I have 30 days) . And I need your and the community support to achieve this. And once again sorry for the working delay from my side. As you said I install git-svn and followed this. http://andy.delcambre.com/2008/03/04/git-svn-workflow.html but when i execute git svn fetch command it takes lot of time and after some extent it breaks. So what i did was just check out eclipse plugin module and deleted all .svn files of it and locally added it in to my cayenne trunk/modeler . As you mentioned it is not compilable due to the changes of code base. So what i tried is just follow the current flow of Main class and do the modifications. And tried to run Cayenne modeler. But i am stuck with some point and it is throwing following exception. Exception in thread "AWT-EventQueue-0" org.apache.cayenne.ConfigurationException: [v.3.1-SNAPSHOT Jun 12 2011 04:54:53] DI container has no binding for key <BindingKey: org.apache.cayenne.extentions.modeler.PluginApplication> at org.apache.cayenne.di.spi.DefaultInjector.getProvider(DefaultInjector.java:123) But i create a patch of my current position. And need some help to go on with this. And finally i will promise that kind of delay will not happen from my side. -- *~Thanks & Regards~* *** * P.A.Eshan Sudharaka Dept of Computer Science and Engineering University of Moratuwa Sri Lanka http://esudharaka.blogspot.com/ -- Regards, Ksenia Khailenko
|View raw message


text:
Printable Calendar January 2019 Word
Calendar printing is currently participating in an important role in the wonderful world of advertising and campaign, and it is thought to be the best promotional tool for every corporation and business. It is the perfect way to remain in front of your clients or people throughout the year. Personalised calendar printing is an excellent approach to producing your make on life's daily activities.
Whatever the company, you can identify calendars anywhere. You could have us provide you with a customized calendar, promotional calendar or you can also pick a inventory calendar, in support of add your information. Custom produced table calendars will be the ideal ways to remain connected with your visitors.
printable calendar january 2019 word
December 2019 Word Calendar Printable Calendar January 2019 Word – 15851
Blank Calendar For January 2019 Printable Calendar January 2019 Word – 15849
Just take a lot of your own artistic photographs from your idea and you are certain to locate a couple of excellent ones you may utilize for calendar printing, all for free. A calendar printing has an important role in promoting your organization as well as their expert services.
Unlike online advertising and classic television set advertising campaigns that will be high priced, calendar printing is very a delicate ways to get your subject matter across to your audience, and also increase your presence. Calendar printing is simply one of the biggest fields in the company of printing. It's the absolute best ways to realize their customers and also full load the business enterprise purposes. Wall calendar printing is one of the few methods it is possible to guarantee individuals are in touch with your brand throughout the year.
You will be ready to utilize month-to-month webpages and place information about your merchandise or services to every. For smaller companies, the multiple pages supply a few promotional opportunities. Choose wire-o binding if you would like calendar webpages to be easily detachable without tearing.
January 2019 Calendar Printable Template #printablecalendar Printable Calendar January 2019 Word – 15850
Utilizing our customized calendar request you can customise your calendar matching to your requirement and want. There's also various ways to bind your calendar. Besides that, calendars are inherently valuable. A calendar is a present that can last a total calendar season. Since almost all of our stitch-bound calendars are made with full-color offset and digital printing, then you're assured to obtain the high quality results that you are worthy of.
Our calendars maintain from 12-32 internet pages, and you might incorporate gap drilling to make your calendars easy to hold on. If you produce your own calendar, you're building a marketing tool that will persist for an extended moment. In the event that you make your own calendar for promotional purposes, the choices are endless.
Just about everyone applies a calendar in 1 way or the other. The calendar's been in existence for a long time, with distinctive eras together with ethnicities building their own spin on it, using the moon or the actors for helpful information to determining the number of days over the complete calendar year. Plainly additionally, it may help us to figure out the real day and also to track specific occasions, including a countdown to a marriage ceremony or possibly a trip. If you're searching for a typical monthly or every year 2017 calendar that you may look at our Online Calendar" webpage. The most famous calendars move forward first. Corporate and business calendars are available in many figures and price mounting brackets. Short term calendars are an excellent method of save dollars.