Search results for "Neuroblast"
showing 10 items of 348 documents
Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic …
2015
Abstract Purpose: We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective–retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183). Experimental Design: Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) we…
Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of r…
2015
BackgroundAcquired resistance to BRAF inhibitors (BRAFi) is a near-universal phenomenon caused by numerous genetic and non-genetic alterations. In this study, we evaluated the spectrum, onset, pattern of progression, and subsequent clinical outcomes associated with specific mechanisms of resistance.MethodsWe compiled clinical and genetic data from 100 patients with 132 tissue samples obtained at progression on BRAFi therapy from 3 large, previously published studies of BRAFi resistance. These samples were subjected to whole-exome sequencing and/or polymerase chain reaction-based genetic testing.ResultsAmong 132 samples, putative resistance mechanisms were identified in 58%, including NRAS o…
Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial.
2011
Abstract Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With…
Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial
2015
Background: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. Patients and methods: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculate…
Impact of Baseline Covariates and Prior Therapy on the Efficacy of Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment
2014
ABSTRACT Aim: Expanding RAS analyses beyond KRAS exon 2 is important in selecting patients (pts) for pmab treatment. Here we present prespecified subgroup analyses from a phase 3 randomised second-line pmab + FOLFIRI vs FOLFIRI study in metastatic colorectal cancer (mCRC) pts. Methods: Progression-free (PFS) and overall survival (OS) were co-primary endpoints. KRAS exon 2 wild-type (WT) samples were tested for mutations in KRAS exons 3/4, NRAS exons 2/3/4 and BRAF exon 15 via bidirectional Sanger sequencing and WAVE-based SURVEYOR®. PFS and OS subgroup analyses were performed by randomisation stratification factors (ECOG performance status [PS], prior bevacizumab [bev]/prior oxaliplatin [ox…
New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: Do all roads lead to RAS?
2015
Abstract: Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid b…
Tumour Shrinkage and Response Outcomes During Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment
2014
ABSTRACT Aim: Tumour shrinkage/response are important outcomes for patients (pts) with metastatic colorectal cancer (mCRC) as they may delay progression and ultimately improve survival. Here we report tumour response data for pts with RAS WT mCRC treated with FOLFIRI ± pmab. Methods: 181 was a phase 3 randomised study of second-line pmab + FOLFIRI vs FOLFIRI alone in pts with previously treated mCRC. KRAS exon 2 wild-type (WT) samples from this study were tested for mutations in KRAS exons 3/4 and NRAS exons 2/3/4 via bidirectional Sanger sequencing and WAVE-based SURVEYOR® to identify pts with RAS WT tumours (no mutations in KRAS/NRAS exons 2, 3 or 4). Objective response rates (ORRs) and m…
KRAS/NRAS and BRAF Mutations in the 20050181 Study of Panitumumab + FOLFIRI for the 2ND-Line Treatment of Metastatic Colorectal Cancer: Updated Analy…
2014
Validation of the High-Risk Prognostic Score Defined By the Presence of Mutations in NRAS or TP53 in a Cohort of 497 Patients with Acute Myeloid Leuk…
2020
INTRODUCTION Older AML patients have a different mutational landscape compared to younger patients. The prognostic classification of AML proposed by the European Leukemia Net (2017) is based on the presence of mutations in FLT3 (ITD), NPM1, CEBPA, RUNX1, ASXL1 and TP53. However, our group has identified a high-risk prognostic score in older patients with AML, who are undergoing treatment with azacitidine or low-dose cytarabine plus fludarabine, which predict a shorter survival. OBJECTIVE Validation of the previously identified high-risk prognostic score, defined by the presence of mutations in NRAS or TP53, in 3 cohorts of patients with AML who have been studied by NGS with a custom panel i…
Peripheral neuroblastic tumors with genotype-phenotype discordance: A report from the Children's Oncology Group and the International Neuroblastoma P…
2012
Background Of 4,706 peripheral neuroblastic tumors (pNTs) registered on the Children’s Cancer Group and Children’s Oncology Group Neuroblastoma Study between 1989 and 2010, 51 cases (1.1%) had genotype-phenotype discordance characterized by MYCN amplification (indicating poor prognosis) and Favorable Histology (indicating better prognosis).