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Clinical Trial And Colorectal Cancer

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https://www.readbyqxmd.com/read/30317148/matching-the-model-with-the-evidence-comparing-discrete-event-simulation-and-state-transition-modeling-for-time-to-event-predictions-in-a-cost-effectiveness-analysis-of-treatment-in-metastatic-colorectal-cancer-patients
#1
Koen Degeling, Mira D Franken, Anne M May, Martijn G H van Oijen, Miriam Koopman, Cornelis J A Punt, Maarten J IJzerman, Hendrik Koffijberg
BACKGROUND: Individual patient data, e.g. from clinical trials, often need to be extrapolated or combined with additional evidence when assessing long-term impact in cost-effectiveness modeling studies. Different modeling methods can be used to represent the complex dynamics of clinical practice; the choice of which may impact cost-effectiveness outcomes. We compare the use of a previously designed cohort discrete-time state-transition model (DT-STM) with a discrete event simulation (DES) model...
October 11, 2018: Cancer Epidemiology
https://www.readbyqxmd.com/read/30315379/survival-outcome-and-prognostic-model-of-patients-with-colorectal-cancer-on-phase-1-trials
#2
Audrey E Kam, Gopichand Pendurti, Umang H Shah, Mohammad H Ghalib, Imran Chaudhary, Jennifer Chuy, Lakshmi Rajdev, Andreas Kaubisch, Santiago Aparo, Ioannis Mantzaris, Sanjay Goel
Background Patients with metastatic colorectal cancer (mCRC) who progress on standard therapies may be eligible for phase I trials. To better delineate the risk-benefit ratio, we assessed toxicities, clinical outcomes and prognostic factors. Methods Records of mCRC patients on phase I trials at our institution over 18 years were reviewed. Univariable (UVA) and multivariable analyses (MVA) were undertaken and a prognostic model developed. Results There were 187 enrollments on 37 phase I trials. Median age was: 59 (29-83) years and number of prior therapies: 3 (0-8)...
October 12, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/30315349/histamine-targets-myeloid-derived-suppressor-cells-and-improves-the-anti-tumor-efficacy-of-pd-1-pd-l1-checkpoint-blockade
#3
Hanna Grauers Wiktorin, Malin S Nilsson, Roberta Kiffin, Frida Ewald Sander, Brianna Lenox, Anna Rydström, Kristoffer Hellstrand, Anna Martner
Myeloid-derived suppressor cells (MDSCs) are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive reactive oxygen species (ROS) via the myeloid cell NADPH oxidase (NOX2). Histamine dihydrochloride (HDC), a NOX2 inhibitor, exerts anti-cancer efficacy in experimental tumor models but the detailed mechanisms are insufficiently understood. To determine effects of HDC on the MDSC compartment we utilized three murine cancer models known to entail accumulation of MDSC, i...
October 12, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/30315134/evaluation-of-a-novel-liquid-biopsy-based-coloscape-assay-for-mutational-analysis-of-colorectal-neoplasia-and-triage-of-fit-patients-a-pilot-study
#4
Mauro Scimia, Jinwei Du, Francesco Pepe, Maria Antonia Bianco, Silvana Russo Spena, Farah Patell-Socha, Qing Sun, Michael J Powell, Umberto Malapelle, Giancarlo Troncone
Circulating cell free tumour derived nucleic acids are becoming recognised as clinically significant and extremely useful biomarkers for detection of cancer and for monitoring the progression of targeted drug therapy and immunotherapy. Screening programmes for colorectal cancer in Europe use the Fetal Immunochemical Test (FIT) test as a primary screener. FIT+ patients are referred to immediate colonoscopy and the positive predictive value (PPV) is usually 25%. In this article, we report a study employing the ColoScape assay panel to detect mutations in the APC, KRAS, BRAF and CTNNB1 genes, in order to collect preliminary performance indicators and plan a future, larger population study...
October 12, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/30309639/a-contemporary-update-on-the-role-of-stereotactic-body-radiation-therapy-sbrt-for-liver-metastases-in-the-evolving-landscape-of-oligometastatic-disease-management
#5
REVIEW
Tyler P Robin, David Raben, Tracey E Schefter
Metastases to the liver are common, and stereotactic body radiation therapy (SBRT) is a recognized tool for ablation of liver metastases. Colorectal cancers commonly metastasize to the liver, and long-term survival is possible after metastasectomy. However, many patients are not candidates for surgical resection, which opened the door to early studies investigating noninvasive techniques such as liver SBRT. Multiple prospective trials have demonstrated excellent local control with this approach coupled with an excellent safety record...
October 2018: Seminars in Radiation Oncology
https://www.readbyqxmd.com/read/30294606/dual-her2-inhibition-strategies-in-the-management-of-treatment-refractory-metastatic-colorectal-cancer-history-and-status
#6
REVIEW
Ozkan Kanat, Hulya Ertas, Burcu Caner
Human epidermal growth factor receptor 2 (HER2) signaling pathway activation has been identified as a contributor to de novo or acquired resistance to epidermal growth factor receptor (EGFR) inhibitors in a small subset of patients with metastatic colorectal cancer (mCRC). Dual anti-HER2-targeted treatment exhibits strong antitumor activity in preclinical models of HER2-positive mCRC, supporting its testing in clinical trials. The HERACLES trial at four Italian academic cancer centers has confirmed the effectiveness of dual blockage of HER2 with trastuzumab plus lapatinib in patients with heavily pretreated HER2-positive mCRC, refractory to the anti-EGFR antibodies cetuximab or panitumumab...
October 6, 2018: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/30290640/a-meta-analysis-of-safety-and-efficacy-of-regorafenib-for-refractory-metastatic-colorectal-cancer
#7
Wu-Song Xue, Si-Ye Men, Wei Liu, Reng-Hai Liu
BACKGROUND: Patients with metastatic colorectal cancer (mCRC) often suffer from progressive disease despite previous therapy. It has been a great challenge for those patients. In 2012, regorafenib was approved for mCRC. In this meta-analysis, we aimed to collect and present existing data to explorethe clinical use of regorafenib. METHODS: The online electronic databases, such as PubMed, Embase, and the Cochrane library, updated to November 2017 were systematically searched...
October 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/30281700/treatment-of-patients-with-metastatic-colorectal-cancer-and-poor-performance-status-current-evidence-and-challenges
#8
Lucila Soares da Silva Rocha, Rachel P Riechelmann
Patients with unresectable metastatic colorectal cancer live for a median of three years when treated with standard therapies. While the evidence guiding cancer-directed treatment of this disease comes from phase III trials that have mostly enrolled patients with good performance status, some patients present with poor clinical conditions. The best treatment for these patients remains to be determined. We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status, defined as Eastern Cooperative Oncology Group performance status ≥2...
September 21, 2018: Clinics
https://www.readbyqxmd.com/read/30275242/tumor-sidedness-and-enriched-gene-groups-for-efficacy-of-first-line-cetuximab-treatment-in-metastatic-colorectal-cancer
#9
Yu Sunakawa, Kaoru Mogushi, Heinz-Josef Lenz, Wu Zhang, Akihito Tsuji, Takehiro Takahashi, Tadamichi Denda, Ken Shimada, Mitsugu Kochi, Masato Nakamura, Masahito Kotaka, Yoshihiko Segawa, Hiroaki Tanioka, Yuji Negoro, Miriana Moran, Stephanie H Astrow, Jack Hsiang, Craig Stephens, Masashi Fujii, Wataru Ichikawa
Molecular differences in tumor locations may contribute to the sidedness-specific response to cetuximab in metastatic colorectal cancer (mCRC). We investigated genes associated with the response to cetuximab treatment depending on tumor sidedness. Our study included 77 mCRC patients (13/63, right/left) with KRAS exon2 wild-type tumors from phase II trials of first-line therapy with cetuximab. Expression levels of 2551 genes were measured in tissue samples by HTG EdgeSeq Oncology Biomarker Panel. Univariate Cox regression analysis using log2 values of counts per million (CPM) was conducted in each sidedness to assess associations with clinical outcomes, and to define the optimal cutoff-point for clinically significant genes...
October 1, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/30272836/phase-ii-feasibility-study-of-a-weight-loss-intervention-in-female-breast-and-colorectal-cancer-survivors-swog-s1008
#10
Heather Greenlee, Danika L Lew, Dawn L Hershman, Vicky A Newman, Lisa Hansen, Sheri J Hartman, Judith Korner, Zaixing Shi, Christine L Sardo Molmenti, Antoine Sayegh, Lou Fehrenbacher, Shelly Lo, Jennifer Klemp, Kristine Rinn, John M Robertson, Joseph Unger, Julie Gralow, Kathy Albain, Robert Krouse, Carol Fabian
OBJECTIVE: This study aimed to test the feasibility of a 12-month weight loss intervention using telephone-based counseling plus community-situated physical activity (PA) in female breast cancer (BC) and colorectal cancer (CRC) survivors. METHODS: This multisite cooperative group study enrolled sedentary, female, postmenopausal BC and CRC survivors with BMI ≥ 25 kg/m2 to receive 12-month fitness center memberships and telephone counseling encouraging 150 min/wk of PA and a 500-kcal/ddecrease in energy intake...
October 2018: Obesity
https://www.readbyqxmd.com/read/30268921/clinicopathological-differences-and-survival-outcomes-with-first-line-therapy-in-patients-with-left-sided-colon-cancer-and-rectal-cancer-pooled-analysis-of-2879-patients-from-agitg-max-coin-focus2-opus-crystal-and-coin-b-trials-in-the-arcad-database
#11
Mohamed E Salem, Jun Yin, Benjamin A Weinberg, Lindsay A Renfro, Levi D Pederson, Timothy S Maughan, Richard A Adams, Eric Van Cutsem, Alfredo Falcone, Niall C Tebbutt, Matthew T Seymour, Eduardo Díaz-Rubio, Enrique Aranda, Carsten Bokemeyer, Volker Heinemann, Harpreet Wasan, Aimery de Gramont, Axel Grothey, Qian Shi, Daniel J Sargent, John L Marshall
PURPOSE: Patients with left-sided colon tumours have better survival and respond differently to biologics compared with patients with right-sided tumours. Left-sided colon tumours and rectal cancers are often grouped together. Herein, we examined the clinicopathological differences and outcomes between left-sided colon and rectal cancers. PATIENTS AND METHODS: Data from 2879 metastatic colorectal cancer patients enrolled on six first-line clinical trials during 2004-2010 were pooled...
September 27, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/30263093/modulation-of-genomic-and-epigenetic-end-points-by-celecoxib
#12
Alberto Izzotti, Sebastiano La Maestra, Rosanna T Micale, Alessandra Pulliero, Marta Geretto, Roumen Balansky, Silvio De Flora
Celecoxib, a nonsteroidal anti-inflammatory drug that selectively targets cyclooxygenase-2, is a promising cancer chemopreventive agent. However, safety concerns have been raised in clinical trials evaluating its ability to prevent colorectal adenomas. The rationale for the herein reported studies was to analyze genomic and epigenetic end-points aimed at investigating both the chemopreventive properties of celecoxib towards cigarette smoke-associated molecular alterations and its possible adverse effects. We carried out three consecutive studies in mice treated with either smoke and/or celecoxib...
September 14, 2018: Oncotarget
https://www.readbyqxmd.com/read/30262136/bevacizumab-biosimilar-bevz92-versus-reference-bevacizumab-in-combination-with-folfox-or-folfiri-as-first-line-treatment-for-metastatic-colorectal-cancer-a-multicentre-open-label-randomised-controlled-trial
#13
Alvaro Romera, Sergiy Peredpaya, Yaroslav Shparyk, Igor Bondarenko, Giovanni Mendonça Bariani, Kathia Cristina Abdalla, Enrique Roca, Fábio Franke, Felipe Melo Cruz, Anita Ramesh, Vikas Ostwal, Pradeep Shah, Sajeed Abdul Rahuman, Alexandra Paravisini, Camino Huerga, Ana Del Campo García, Susana Millán
BACKGROUND: BEVZ92 is a proposed biosimilar to bevacizumab. The two molecules have similar physicochemical and functional properties in in-vitro and preclinical studies. In this clinical study, we compared the pharmacokinetic profile, efficacy, safety, and immunogenicity of BEVZ92 with reference bevacizumab as a first-line treatment in patients with metastatic colorectal cancer. METHODS: We did a randomised, open-label trial at 15 centres in Argentina, Brazil, India, Spain, and Ukraine...
September 24, 2018: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/30257369/pharmacological-insights-into-antioxidants-against-colorectal-cancer-a-detailed-review-of-the-possible-mechanisms
#14
REVIEW
Sivapragasam Gothai, Katyakyini Muniandy, Charles Gnanaraj, Ibrahim Abdel Aziz Ibrahim, Naiyer Shahzad, Saeed S Al-Ghamdi, Nahla Ayoub, Vishnu Priya Veeraraghavan, S Suresh Kumar, Norhaizan Mohd Esa, Palanisamy Arulselvan
Colorectal cancer (CRC) is ranked as the fourth most lethal and commonly diagnosed cancer in the world according to the National Cancer Institute's latest report. Treatment methods for CRC are constantly being studied for advancement, which leads for more clinically effective cancer curing strategy. Patients with prolonged chronic inflammation caused by ulcerative colitis or similar inflammatory bowel disease are known to have high risks of developing CRC. But at a molecular level, oxidative stress due to reactive oxygen species (ROS) is an important trigger for cancer...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30257347/role-of-transmembrane-glycoprotein-mucin-1-muc1-in-various-types-of-colorectal-cancer-and-therapies-current-research-status-and-updates
#15
REVIEW
Mei Guo, Chengzhong You, Jun Dou
Colorectal carcinoma (CRC) is the third most common malignant tumor in the world. In recent years, the morbidity and mortality of CRC have increased in the world due to increasingly ageing population, modern dietary habits, environmental change, genetic disorders and chronic intestinal inflammation. Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic CRC remains low. Therefore, novel effective treatment strategies for primary or metastatic CRC have emerged to enhance cure rate as well as elongation of patient's survival...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30252687/diagnostic-assessment-of-assumptions-for-external-validity-an-example-using-data-in-metastatic-colorectal-cancer
#16
Michael A Webster-Clark, Hanna K Sanoff, Til Stürmer, Sharon Peacock Hinton, Jennifer L Lund
BACKGROUND: Methods developed to estimate intervention effects in external target populations assume that all important effect measure modifiers have been identified and appropriately modeled. Propensity score-based diagnostics can be used to assess the plausibility of these assumptions for weighting methods. METHODS: We demonstrate the use of these diagnostics when assessing the transportability of treatment effects from the standard of care for metastatic colorectal cancer control arm in a phase III trial (HORIZON III) to a target population of 1,942 Medicare beneficiaries aged 65+ years...
September 24, 2018: Epidemiology
https://www.readbyqxmd.com/read/30252681/clinical-outcome-after-rectal-replacement-with-side-to-end-colon-j-pouch-or-straight-colorectal-anastomosis-following-total-mesorectal-excision-a-swiss-prospective-randomized-multicenter-trial-sakk-40-04
#17
Walter R Marti, Gaudenz Curti, Heinz Wehrli, Felix Grieder, Michael Graf, Beat Gloor, Markus Zuber, Nicolas Demartines, Fabrizio Fasolini, Bruno Lerf, Christoph Kettelhack, Christiane Andrieu, Martin Bigler, Stefanie Hayoz, Karin Ribi, Christian Hamel
OBJECTIVE: To compare, in a phase 3, prospective, randomized, multi-center clinical trial functional outcome of reconstruction procedures following total mesorectal excision (TME). SUMMARY BACKGROUND DATA: Intestinal continuity reconstruction following TME is accompanied by postoperative defecation dysfunctions known as "anterior resection syndrome." Commonly used reconstruction techniques are straight colorectal anastomosis (SCA), colon J -pouch (CJP), and side-to-end anastomosis (SEA)...
September 24, 2018: Annals of Surgery
https://www.readbyqxmd.com/read/30250304/intranasal-administration-of-resveratrol-successfully-prevents-lung-cancer-in-a-j-mice
#18
Aymeric Monteillier, Aymone Voisin, Pascal Furrer, Eric Allémann, Muriel Cuendet
Lung cancer is the most lethal cancer in the world. About 80% of lung cancer deaths are linked to tobacco use. As a complement to tobacco control, efficient chemoprevention strategies are needed to tackle lung cancer epidemic. Resveratrol is one of the most studied natural products, notably for its cancer chemoprevention properties. However, its low oral bioavailability has often limited the translation of in vitro activities to in vivo effects. While oral administration of resveratrol effectively inhibited colorectal carcinogenesis, it failed to protect mice from chemically-induced lung carcinogenesis...
September 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30249195/clinical-trial-protocol-of-the-aster-trial-a-double-blind-randomized-placebo-controlled-phase-iii-trial-evaluating-the-use-of-acetylsalicylic-acid-asa-for-enhanced-early-detection-of-colorectal-neoplasms
#19
Kaja Tikk, David Czock, Walter E Haefeli, Annette Kopp-Schneider, Hermann Brenner
ᅟ: Immunochemical fecal occult blood tests (iFOBTs) are increasingly used for colorectal cancer (CRC) screening. In our preceding observational study, sensitivity for detecting advanced colorectal neoplasms by iFOBT was 70.8% among users of low-dose acetylsalicylic acid compared with 35.9% among non-users (p = 0.001), whereas there were only very small differences in specificity. In receiver operating characteristics (ROC) analyses, the area under the curve (AUC) was much higher for acetylsalicylic acid users than for non-users, with particularly strong differences in men (0...
September 24, 2018: BMC Cancer
https://www.readbyqxmd.com/read/30248285/does-hyperthermic-preconditioning-affect-the-rate-of-surgical-site-infection-rate-and-inflammatory-reaction-in-colorectal-cancer-patients-a-prospective-randomized-clinical-trial
#20
Wafi Attaallah, Leyla Semiha Şen, Ahmet Özdemir Aktan, Emel Demiralp Ekşioğlu, Zeynep Eti, Sertaç Ata Güler, Asım Cingi
OBJECTIVES: Hyperthermic preconditioning has been shown to protect against different insults in experimental studies. However, clinical studies assessing its effects remain limited. The aim of this study was to investigate the effects of hyperthermic preconditioning on the rate of surgical site infection and inflammatory reaction in patients undergoing elective colorectal cancer surgery. MATERIAL AND METHODS: Patients with colorectal cancer, scheduled to undergo elective surgery were enrolled in this prospective randomized study...
September 11, 2018: Turkish Journal of Surgery
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