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https://www.readbyqxmd.com/read/28431395/correlation-of-genomic-alterations-assessed-by-next-generation-sequencing-ngs-of-tumor-tissue-dna-and-circulating-tumor-dna-ctdna-in-metastatic-renal-cell-carcinoma-mrcc-potential-clinical-implications
#1
Andrew W Hahn, David M Gill, Benjamin Maughan, Archana Agarwal, Lubina Arjyal, Sumati Gupta, Jessica Streeter, Erin Bailey, Sumanta K Pal, Neeraj Agarwal
INTRODUCTION: Tumor tissue and circulating tumor DNA (ctDNA) next-generation sequencing (NGS) testing are frequently performed to detect genomic alterations (GAs) to help guide treatment in metastatic renal cell carcinoma (mRCC), especially after progression on standard systemic therapy. Our objective was to assess if GAs detected by ctDNA NGS are different from those detected by tumor tissue NGS, specifically in patients with mRCC, and if these platforms are interchangeable or complimentary...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429452/real-world-experience-of-the-feasibility-and-tolerability-of-the-2-1-dosing-schedule-with-sunitinib-in-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-in-australia
#2
Megan Crumbaker, Alexander Guminski, Howard Gurney, Dhanusha Sabanathan, Shirley Wong, Nick Pavlakis
AIM: Sunitinib is a first-line treatment option for metastatic renal cell carcinoma (mRCC) funded by the Australian Pharmaceutical Benefits Scheme. Toxicities are common with the standard schedule leading to alternative dosing schedules to be suggested. We reviewed Australian treatment practices to evaluate the safety and outcomes of patients on a 2 weeks on, 1 week off treatment schedule (2/1). METHODS: We performed a retrospective review of 63 patients with mRCC treated with first-line sunitinib on a 2/1 schedule at four Australian centers...
April 21, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28423742/novel-potential-predictive-markers-of-sunitinib-outcomes-in-long-term-responders-versus-primary-refractory-patients-with-metastatic-clear-cell-renal-cell-carcinoma
#3
Javier Puente, Nuria Laínez, Marta Dueñas, María José Méndez-Vidal, Emilio Esteban, Daniel Castellano, Mónica Martinez-Fernández, Laura Basterretxea, María José Juan-Fita, Luis Antón, Luis León, Julio Lambea, Begoña Pérez-Valderrama, Sergio Vázquez, Cristina Suarez, Xavier Garcia Del Muro, Enrique Gallardo, José Pablo Maroto, M Luz Samaniego, Beatriz Suárez-Paniagua, Julián Sanz, Jesús M Paramio, Sogug Spanish Oncology Genitourinary Group
BACKGROUND: Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. PATIENTS AND METHODS: Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset)...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422035/-new-therapeutic-schedules-of-sunitinib-current-evidence-regarding-the-2-1-scheme
#4
Ignacio Puche-Sanz, José Francisco Flores-Martín, Fernando Vázquez-Alonso, Juan Moreno-Jiménez, José Manuel Cózar-Olmo
INTRODUCTION: In 2006, sunitinib approval by the FDA was a real revolution for the treatment of metastatic renal cell carcinoma (mRCC). However, considerable rates of dose reductions and therapeutic suppressions with the standard regimen (4:2) have forced the search for new schedule proposals in order to optimize the balance between side effects and oncologic efficacy. Among these new proposals, the 2:1 scheme is the one that has generated more expectations. OBJECTIVE: The objective of this paper is to make a review and critical discussion of current evidence about the new schedules of treatment with sunitinib...
April 2017: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/28416753/synergistic-effects-of-the-immune-checkpoint-inhibitor-ctla-4-combined-with-the-growth-inhibitor-lycorine-in-a-mouse-model-of-renal-cell-carcinoma
#5
Xiezhao Li, Peng Xu, Chongshan Wang, Naijin Xu, Abai Xu, Yawen Xu, Takuya Sadahira, Motoo Araki, Koichiro Wada, Eiji Matsuura, Masami Watanabe, Junxia Zheng, Pinghua Sun, Peng Huang, Yasutomo Nasu, Chunxiao Liu
Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation)...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414866/characterizing-the-outcomes-of-metastatic-papillary-renal-cell-carcinoma
#6
John Connor Wells, Frede Donskov, Anna P Fraccon, Felice Pasini, Georg A Bjarnason, Benoit Beuselinck, Jennifer J Knox, Sun Young Rha, Neeraj Agarwal, Isaac Alex Bowman, Jae-Lyun Lee, Sumanta K Pal, Sandy Srinivas, Douglas Scott Ernst, Ulka N Vaishampayan, Lori A Wood, Robin Simpson, Guillermo De Velasco, Toni K Choueiri, Daniel Y C Heng
Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC...
April 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#7
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28409322/tyrosine-kinase-inhibitors-reprogramming-immunity-in-renal-cell-carcinoma-rethinking-cancer-immunotherapy
#8
REVIEW
L M A Aparicio, I P Fernandez, J Cassinello
The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity...
April 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28409120/sunitinib-enables-a-clinical-and-pathological-complete-remission-of-metastatic-renal-cell-carcinoma-mrcc
#9
Bo Peng, Jin Gong
Renal cell carcinoma (RCC) is the most common renal cancer, and has a poor prognosis in individuals with metastases (mRCC). In this report, we describe a 48-year-old woman with unresectable multiple liver metastases and a colonic metastasis of RCC who was treated with sunitinib in combination with hepatic microwave ablation and obtained a clinical and pathological complete remission. We consider that sunitinib combined with microwave ablation can prevent unresectable hepatic metastases of RCC from evolving, and that sunitinib alone can achieve clinical and pathological remission in patients with colonic metastasis of RCC...
May 2017: Urology Case Reports
https://www.readbyqxmd.com/read/28405544/predictive-factors-for-second-line-therapy-in-metastatic-renal-cell-carcinoma-a-retrospective-analysis
#10
Hendrik Eggers, Philipp Ivanyi, Mareike Hornig, Viktor Grünwald
Currently, about 50% of patients with metastatic renal cell carcinoma (mRCC) receive a second-line therapy. Therefore, the choice at each subsequent treatment line remains an important issue. In this retrospective study, we sought to identify pretreatment clinical parameters that could predict the likelihood of a patient receiving a second-line therapy. One hundred and sixty-one mRCC patients who received targeted therapy were evaluated. Descriptive statistics, Kaplan-Meier overall survival (OS), Cox regression, and binary logistic regression models were used for data analysis...
2017: Journal of Kidney Cancer and VHL
https://www.readbyqxmd.com/read/28404979/in-vivo-relation-between-plasma-concentration-of-sorafenib-and-its-safety-in-chinese-patients-with-metastatic-renal-cell-carcinoma-a-single-center-clinical-study
#11
Haixing Mai, Jun Huang, Yuanyuan Zhang, Nang Qu, Hengyan Qu, Guo-Hui Mei, Jiannan Liu, Xiaojie Xu, Lijun Chen
This single-center, observational study analyzed the association between plasma concentration of sorafenib and its safety and efficacy in Chinese patients with metastatic renal cell carcinoma (mRCC). Adult patients with RCC (n = 94), treated with sorafenib were enrolled between January 2014 and January 2015. Sorafenib plasma concentrations were measured by liquid chromatography-tandem mass spectrometry. Safety and efficacy variables were evaluated using National Cancer Institute-Common Toxicity Criteria for Adverse Events and Response Evaluation Criteria in Solid Tumors criteria...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403496/-interdisciplinary-recommendations-for-the-treatment-of-metastatic-renal-cell-carcinoma
#12
Kurt Miller, Lothar Bergmann, Christian Doehn, Jürgen Gschwend, Ulrich Keilholz
Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure...
February 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28401381/antiangiogenic-therapy-combined-with-immune-checkpoint-blockade-in-renal-cancer
#13
REVIEW
Teele Kuusk, Laurence Albiges, Bernard Escudier, Nikolaos Grivas, John Haanen, Thomas Powles, Axel Bex
Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors is the current first-line treatment in metastatic renal cell carcinoma (mRCC). Immunotherapy with checkpoint inhibitor has been recently added to the armamentarium of mRCC treatment. These therapies are based on treatment with antibodies that block programmed cell death-1 (PD-1), programmed cell death ligand 1 (PD-L1) pathways, demonstrating impressive response rates and improved survival in several tumour types. So far, nivolumab is the only approved anti-PD-1 monoclonal antibody after VEGF therapy in mRCC...
April 11, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28392154/sunitinib-4-2-versus-2-1-schedule-for-patients-with-metastatic-renal-cell-carcinoma-tertiary-care-hospital-experience
#14
Mai Ezz El Din
BACKGROUND: Sunitinib first-line treatment is one of the standards of care in metastatic renal cell carcinoma (mRCC). However, the adverse events associated with its use can hinder adequate dosing and hence have detrimental effects on treatment outcome. Alternative schedules, such as 2-weeks-on treatment and 1-week-off treatment (2/1 schedule), might solve this dilemma. Therefore, an analysis was performed to compare both schedules in terms of toxicity and efficacy. PATIENTS AND METHODS: Data regarding first-line sunitinib treatment of mRCC patients using the 4/2 and 2/1 schedules were collected...
January 4, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28387134/a-rapid-identification-method-for-calamine-using-near-infrared-spectroscopy-based-on-multi-reference-correlation-coefficient-method-and-back-propagation-artificial-neural-network
#15
Yangbo Sun, Long Chen, Bisheng Huang, Keli Chen
As a mineral, the traditional Chinese medicine calamine has a similar shape to many other minerals. Investigations of commercially available calamine samples have shown that there are many fake and inferior calamine goods sold on the market. The conventional identification method for calamine is complicated, therefore as a result of the large scale of calamine samples, a rapid identification method is needed. To establish a qualitative model using near-infrared (NIR) spectroscopy for rapid identification of various calamine samples, large quantities of calamine samples including crude products, counterfeits and processed products were collected and correctly identified using the physicochemical and powder X-ray diffraction method...
January 1, 2017: Applied Spectroscopy
https://www.readbyqxmd.com/read/28385611/description-of-the-eurotarget-cohort-a-european-collaborative-project-on-targeted-therapy-in-renal-cell-cancer-genetic-and-tumor-related-biomarkers-for-response-and-toxicity
#16
Loes F M van der Zanden, Sita H Vermeulen, Arna Oskarsdottir, Jake S F Maurits, Meta H M Diekstra, Valentin Ambert, Anne Cambon-Thomsen, Daniel Castellano, Achim Fritsch, Jesus Garcia Donas, Rosa Guarch Troyas, Henk-Jan Guchelaar, Arndt Hartmann, Christina Hulsbergen-van de Kaa, Ulrich Jaehde, Kerstin Junker, Anna Martinez-Cardus, Gisli Masson, Jeannette Oosterwijk-Wakka, Marius T Radu, Thorunn Rafnar, Cristina Rodriguez-Antona, Max Roessler, Rob Ruijtenbeek, Kari Stefansson, Anne Warren, Lodewyk Wessels, Tim Eisen, Lambertus A L M Kiemeney, Egbert Oosterwijk
OBJECTIVE: For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort...
April 3, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28381801/association-of-single-nucleotide-polymorphisms-in-stat3-abcb1-and-abcg2-with-stomatitis-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-sunitinib-a-retrospective-analysis-in-japanese-patients
#17
Aimi Watanabe, Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Hideaki Miyake, Masato Fujisawa, Tsutomu Nakagawa, Ikuko Yano, Midori Hirai
Signal transducer and activator of transcription (STAT) 3 is a key factor in homeostasis of the oral mucosa by regulating the production of inflammatory cytokines. Sunitinib is a substrate of P-glycoprotein (multidrug resistance (MDR)-1/ABCB1) and breast-cancer resistance protein (BCRP/ABCG2). In this retrospective study, we evaluated the association between sunitinib-induced stomatitis and STAT3, ABCB1, and ABCG2 polymorphisms in patients with metastatic renal cell carcinoma (mRCC). Fifty-two Japanese patients with RCC treated with sunitinib were retrospectively genotyped to elucidate a potential association between STAT3, ABCB1, and ABCG2 polymorphisms and stomatitis development...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28378918/a-pharmacometric-framework-for-axitinib-exposure-efficacy-and-safety-in-metastatic-renal-cell-carcinoma-patients
#18
Emilie Schindler, Michael A Amantea, Mats O Karlsson, Lena E Friberg
The relationships between exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble VEGF receptors (sVEGFR)-1, 2, 3, and soluble stem cell factor receptor (sKIT)), tumor sum of longest diameters (SLD), diastolic blood pressure (dBP) and overall survival (OS) were investigated in a modeling framework. The dataset included 64 metastatic renal cell carcinoma patients (mRCC) treated with oral axitinib. Biomarker time-courses were described by indirect response (IDR) models where axitinib inhibits sVEGFR-1, 2 and 3 production, and VEGF degradation...
April 5, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28368708/design-and-rationale-of-the-metastatic-renal-cell-carcinoma-marcc-registry-a-prospective-academic-and-community-based-study-of-patients-with-metastatic-renal-cell-cancer
#19
Nrupen A Bhavsar, Michael R Harrison, Bradford R Hirsch, Patricia Creel, Steve P Wolf, Greg P Samsa, Amy P Abernethy, Ronit Simantov, Azah Borham, Daniel J George
The Metastatic Renal Cell Cancer Registry, a large, nationally representative, prospective registry of patients with metastatic renal cell carcinoma (mRCC), aims to understand real-world treatment patterns and outcomes of patients with mRCC in routine clinical practice across the United States. This observational study is designed to enroll 500 patients with previously untreated mRCC from approximately 60 academic and community treatment sites; as of December 7, 2016, 500 patients have enrolled at 54 sites...
April 3, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28359734/complications-after-metastasectomy-for-renal-cell-carcinoma-a-population-based-assessment
#20
Christian P Meyer, Maxine Sun, Jose A Karam, Jeffrey J Leow, Guillermo de Velasco, Sumanta K Pal, Steven L Chang, Quoc-Dien Trinh, Toni K Choueiri
Metastasectomy has long been considered a valid treatment option for patients with oligometastatic renal cell carcinoma (oligo-mRCC). However, the literature on complications in this setting is scarce. Our objective was to describe in-hospital complications after metastasectomy in a contemporary cohort of patients with mRCC. Using the National Inpatient Sample database (2000-2011), 45 279 mRCC patients were identified. Of those, 1102 underwent metastasectomies. The metastatic sites were the lungs, bone, liver, lymph nodes, adrenal glands, and brain in, respectively, 52%, 29%, 19%, 14%, 11%, and 3...
March 27, 2017: European Urology
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