Postagens

Mostrando postagens de setembro, 2016

Cleveland Clinic. Your complete Medical Education portal.

http://www.clevelandclinicmeded.com/online/tumorboards/?utm_source=cmeecom&utm_medium=seriesdisplayads_harborside&utm_content=tumorboardseries%2Burl&utm_campaign=065%2B14%2Btumorboard

Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone.

http://www.nature.com/bjc/journal/v111/n12/pdf/bjc2014531a.pdf Tumour responses following a steroid switch from prednisone to  dexamethasone  in castration-resistant prostate cancer patients progressing on  abiraterone . Lorente D 1 ,  Omlin A 2 ,  Ferraldeschi R 1 ,  Pezaro C 1 ,  Perez R 1 ,  Mateo J 1 ,  Altavilla A 1 ,  Zafeirou Z 1 ,  Tunariu N 1 ,  Parker C 3 ,  Dearnaley D 3 ,  Gillessen S 4 , de Bono J 1 ,  Attard G 1 . Author information Abstract BACKGROUND: Abiraterone  is a CYP17A1 inhibitor that improves survival in castration-resistant prostate cancer (CRPC).  Abiraterone  is licensed in combination with prednisone 5 mg twice daily to prevent a syndrome of secondary mineralocorticoid excess. We hypothesised that a 'steroid switch' from prednisone to  dexamethasone  would induce secondary responses in patients progressing on  abiraterone  and prednisone 5 mg b.i.d. METHODS: We performed a 'steroid switch' in patients with CRPC at PSA p

Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=11383 ABSTRACT ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR. Mutation rate was 31.3% (5/16) (n=3; de novo , n=2; acquired). D538G was the most frequent mutation (n=3), followed by Y537N and Y537S (n=2). One patient showed multiple ESR1 mutations. Mutations were enriched during therapy. Progression-free survival (PFS) and overall survival (

Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials of the AGO Study Group, GINECO and NSGO

Highlights •To detect the effect of young age on survival in ovarian cancer patients. •A meta-database analysis of 5055 ovarian cancer patients. •Potential confounding and effect measure modification are considered. •Prognostic factors of survival are similar in patients under and over 40 years of age. •Young age at diagnosis of ovarian cancer improves survival. Abstract Objectives We evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients < and >40 years of age with advanced epithelial ovarian cancer. Methods A total of 5055 patients of the AGO, GINECO, NSGO intergroup studies AGO-OVAR 3, 5, 7 and 9 were merged to identify 294 patients <40 years and 4761 patients ≥40 years. We conducted survival analyses and Cox proportional hazard regression models and additionally analysed a very homogeneous subcohort of 405 patients with serou

HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study

http://dx.doi.org/10.1016/S1470-2045(16)30227-3 Summary Background HSD3B1  (1245A>C) has been mechanistically linked to castration-resistant prostate cancer because it encodes an altered enzyme that augments dihydrotestosterone synthesis from non-gonadal precursors. We postulated that men inheriting the  HSD3B1  (1245C) allele would exhibit resistance to androgen-deprivation therapy (ADT). Methods In this multicohort study, we determined  HSD3B1  genotype retrospectively in men treated with ADT for post-prostatectomy biochemical failure and correlated genotype with long-term clinical outcomes. We used data and samples from prospectively maintained prostate cancer registries at the Cleveland Clinic (Cleveland, OH, USA; primary study cohort) and the Mayo Clinic (Rochester, MN, USA; post-prostatectomy and metastatic validation cohorts). In the post-prostatectomy cohorts, patients of any age were eligible if they underwent prostatectomy between Jan 1, 1996, and Dec 31, 2009 (a

EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

http://www.sciencedirect.com/science/article/pii/S0302283816304705 available at www.sciencedirect.com journal homepage: www.europeanurology.com Guidelines EAU–ESTRO–SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent Nicolas Mottet a , * , Joaquim Bellmunt b , c , Michel Bolla d , Erik Briers e , Marcus G. Cumberbatch f , Maria De Santis g , Nicola Fossati h , i , Tobias Gross j , Ann M. Henry k , Steven Joniau l , Thomas B. Lam m , n , Malcolm D. Mason o , Vsevolod B. Matveev p , Paul C. Moldovan q , Roderick C.N. van den Bergh r , Thomas Van den Broeck l , Henk G. van der Poel s , Theo H. van der Kwast t , Olivier Rouvie`re q , Ivo G. Schoots u , Thomas Wiegel v , Philip Cornford w a Department of Urology, University Hospital, St. Etienne, France; b Bladder Cancer Center, Dana-Farber Cancer Institute, Boston, MA, USA; c Harvard Medical School, Boston, MA, USA

FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial

http://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(16)30269-8.pdf FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial Sebastian Stintzing, Dominik P Modest, Lisa Rossius, Markus M Lerch, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christian Lerchenmüller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Swantje Held, Clemens Giessen-Jung, Markus Moehler, Andreas Jagenburg, Thomas Kirchner, Andreas Jung, Volker Heinemann, on behalf of the FIRE-3 investigators Summary Background FIRE-3 compared first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus cetuximab with FOLFIRI plus bevacizumab in patients with KRAS exon 2 wild-type metastatic colore

Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta-analysis

http://www.nature.com/articles/srep06269 Abstract Epidermal growth factor receptor (EGFR) mutation is a reliable and sensitive biomarker for EGFR-TKI therapy in non-small-cell lung cancer (NSCLC). However, detection of EGFR mutation in tissues has obvious limitations. Circulating free DNA (cfDNA) has been reported as an alternative approach for the detection of EGFR mutations. This systematic review and meta-analysis was designed to assess the diagnostic performance of cfDNA, compared with tissues. True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance. 20 eligible studies involving 2012 cases were included in this m

Use of cell free DNA in breast oncology

http://www.sciencedirect.com/science/article/pii/S0304419X16300282 Biochim Biophys Acta. 2016 Apr;1865(2):266-74. doi: 10.1016/j.bbcan.2016.03.006. Epub 2016 Mar 22. Use of cell free DNA in breast oncology. Canzoniero JV 1 , Park BH 2 . Author information Abstract Cell free DNA (cfDNA) are short fragments of nucleic acids present in circulation outside of cells. In patients with cancer, some portion of cfDNA is derived from tumor cells, termed circulating tumor DNA (ctDNA), and contains the same mutations and genetic changes as the cancer. The development of new, more effective methods to detect these changes has led to increased interest in developing ctDNA as a biomarker for cancer. Here we will review current literature on the use of ctDNA, with an emphasis on breast cancer, for cancer detection, prognosis, monitoring response to therapy, and tracking the rise of new mutant subclones.

Circulating Cell Free DNA as the Diagnostic Marker for Ovarian Cancer: A Systematic Review and Meta-Analysis

http://journals.plos.org/plosone/article/asset?id=10.1371%2Fjournal.pone.0155495.PDF Abstract Background Quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detec- tion of ovarian cancer. Many studies have evaluated these approaches, but the results were too inconsistent to be conclusive. This study is the first to systematically evaluate the accuracy of circulating cfDNA for the diagnosis of ovarian cancer by conducting meta-analysis. Methods We searched PubMed, Embase, Cochrane Library and the Chinese National Knowledge Infrastructure (CNKI) databases systematically for relevant literatures up to December 10, 2015. All analyses were conducted using Meta-DiSc1.4 and Stata 12.0 software. Sensitiv- ity, specificity and other measures of accuracy of circulating cfDNA for the diagnosis of ovar- ian cancer were pooled. Meta-regression was performed to identify the sources of heterogeneity. Results

Quantitative analysis of circulating cell-free DNA for correlation with lung cancer survival: a systematic review and meta-analysis.

http://www.jto.org/article/S1556-0864(16)30711-0/pdf ABSTRACT ACCEPTED MANUSCRIPT Introduction: Despite the growing interest in circulating cell-free DNA (cfDNA), no conclusive evidence exists on the value of quantitative analysis of cfDNA for prediction of lung cancer survival. We herein performed a systematic review and meta-analysis of primary studies to estimate the impact of higher baseline cfDNA levels on survival outcomes of lung cancer patients. Methods: A comprehensive search was performed through PubMed, Web of Knowledge and Cochrane databases up to March 2016. The methodological quality of identified studies was assessed by the Newcastle-Ottawa Scale. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, while publication bias was evaluated by funnel plot and Egger’s test. Results: Among the 17 studies identified, 16 studies (n=1723 patients) an