1,720,989 research outputs found
Valutazione dell'attività di pembrolizumab in pazienti con recidiva di glioma di alto-grado e perdita parziale o completa di espressione delle proteine del mismatch repair: studio monocentrico, osservazionale, prospettico
No full textBackground
Pembrolizumab, un inibitore del checkpoint immunitario anti PD-1, ha mostrato un' importante attività in diversi tipi di tumori con fenotipo ipermutato. La perdita di espressione delle proteine del mismatch repair (MMR) all'analisi immunoistochimica sembra essere associata all' ipermutazione nei gliomi di alto-grado (HGG). Questo studio ha valutato l'efficacia e la sicurezza di pembrolizumab in pazienti con recidiva di glioma di alto-grado e perdita immunoistochimica di almeno una delle proteine MMR. Inoltre, sono stati valutati potenziali biomarcatori molecolari che possano predire l'attività di pembrolizumab
Materiali e Metodi
Abbiamo arruolato prospetticamente pazienti con recidiva di HGG e perdita parziale o completa dell'espressione delle proteine MMR. Pembrolizumab è stato somministrato per infusione endovenosa alla dose standard di 200 mg una volta ogni 3 settimane fino a tossicità inaccettabile o progressione della malattia. L'endpoint primario era il tasso di controllo della malattia (DCR). Come analisi esplorative post hoc, sono stati eseguiti il sequenziamento di nuova generazione (NGS) per la valutazione del carico mutazionale del tumore (TMB) e l'immunocolorazione per le cellule T CD8 + e i macrofagi CD68 +.
Risultati
Sono stati selezionati 310 pazienti con recidiva di HGG; 13 di loro con perdita parziale o completa dell' espressione di almeno una delle proteine del MMR sono stati arruolati e trattati con pembrolizumab. Di questi 13 casi, otto avevano una diagnosi di glioblastoma, quattro di astrocitoma anaplastico e uno di oligodendroglioma anaplastico. L'età media era di 43 anni. La DCR è stata del 31% con quattro pazienti che hanno mostrato una stabilità di malattia come miglior risposta e nessuno con risposta parziale o completa. Il TMB variava tra 6,8 e 23,4 mutazioni/megabase. Le mutazioni riscontrate nei pazienti trattati, il TMB, la presenza di cellule T CD8 + e macrofagi CD68 + non sembrano essere associati all'attività di pembrolizumab.
Conclusioni
Pembrolizumab non ha dimostrato alcun beneficio in questa popolazione di pazienti e non sono stati identificati biomarcatori molecolari associati all'attività di pembrolizumab.Background
Pembrolizumab, an anti PD-1 immune checkpoint inhibitor, has shown important activity in several cancers with hypermutated phenotype. Expression loss of mismatch repair (MMR) protein on immunohistochemical analysis appears to be associated with hypermutation in high-grade gliomas. This study evaluated the efficacy and safety of pembrolizumab in patients with HGGs and immunohistochemical loss of at least one MMR protein. In addition, potential molecular biomarkers predicting pembrolizumab activity were evaluated
Materials and Methods
We prospectively enrolled patients with recurrent HGG and partial or complete loss of MMR protein expression. Pembrolizumab was administered by intravenous infusion at the standard dose of 200 mg once every 3 weeks until unacceptable toxicity or disease progression. Primary end point was disease control rate (DCR). As exploratory post hoc analyzes, next generation sequencing (NGS) for the evaluation of tumor mutational burden (TMB) and immunostaining for CD8 + T-cells and CD68 + macrophages were performed.
Results:
310 patients with recurrent HGG were screened; 13 of them with MMR expression loss were enrolled and treated with pembrolizumab. Of these 13 cases, eight were glioblastoma, four anaplastic astrocytoma, and one anaplastic oligodendroglioma. Median age was 43 years. DCR was 31% with four patients showing stable disease as the best response and none with partial or complete response. TMB ranged between 6.8 and 23.4 mutations/megabase. Mutations found in treated patients, TMB, CD8 + T-Cell and CD68 + macrophage do not appear to be associated with pembrolizumab activity.
Conclusions
Pembrolizumab demonstrated no benefit in this patient population and no molecular biomarkers associated with pembrolizumab activity were found
The coming of ramucirumab in the landscape of anti-angiogenic drugs: potential clinical and translational perspectives
No full textAngiogenesis plays a pivotal role in the development and progression of tumors and it represents a crucial target for therapeutic strategies. Until now, regulatory agencies approved antiangiogenic agents targeting the VEGF and multi-target agents carrying antiangiogenic and anti-proliferative effects. They often provide only a modest survival benefit and their role in clinical practice is debated. The limited efficacy may be partially explained by the complexity of the molecular background of angiogenic processes, composed of several pathways interacting with both tumor cells and the microenvironment
Adjuvant therapy for resected early-stage small-cell lung cancer: is now time to rethink about that?
No full textSmall-cell lung cancer (SCLC) has historically been considered a highly chemo-radiosensitive malignancy, rarely susceptible of surgical resection due to advanced stage presentation with bulky nodal disease and frequent systemic involvement. Actually, surgical series documented SCLC in just 2–3% of patients (1) and, although several randomized trials contributed to define the management of extensive and limited stage SCLC, very few data are available for the early stage, possibly resectable, disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Necitumumab in the treatment of non-small-cell lung cancer: clinical controversies
No full textOver the last decade, epidermal growth factor receptor (EGFR) signaling was investigated as a potential target for tyrosine kinase inhibitors in the treatment of non-small-cell lung cancer (NSCLC). Necitumumab is a fully humanized IgG1 monoclonal antibody directed against the binding domain of EGFR, approved in combination with cisplatin-gemcitabine for the first-line treatment of squamous NSCLC. Areas covered: The purpose of this manuscript is to systematically review the state of the art of necitumumab for the treatment of metastatic NSCLC, focusing on predictive factors, cost-effectiveness, and future potential combinations with additional agents. Expert opinion: Despite recent therapeutic advances, platinum-based chemotherapy still represents the most widely used first-line treatment for advanced NSCLC, particularly for the squamous histotype. Necitumumab is nowadays the first targeted agent providing an (statistically significant) additional survival gain to squamous NSCLC patients when combined with first-line chemotherapy at the cost of an increased (although manageable) toxicity, as shown in the SQUIRE trial. Hopefully, improvement in patients' selection by identifying reliable predictive markers and the combination with new agents may help to maximize the benefit of this targeted treatment, which is currently limited by a not optimal cost-benefit ratio
Impressive response to dabrafenib and trametinib plus silybin in a heavily pretreated IDH wild-type glioblastoma patient with BRAFV600E-mutant and SOX2 amplification
No full textIsocitrate dehydrogenase wild-type glioblastoma is the most frequent primary brain tumor in adult patients and its prognosis is still dismal with a median survival of about 1 year. BRAFV600E mutation, an important target for personalized therapy, has been identified in about 3% of these patients, but few data are available from prospective studies on the role of anti-BRAF drugs in adult glioblastoma patients. Moreover, SOX2 gene amplification and overexpression can represent an important mechanism of resistance to BRAF inhibitors by STAT3 gene activation. We present the case of a heavily pretreated 42-year-old man with BRAFV600E mutant and SOX2 amplification glioblastoma having a radiologic and metabolic [analyzed by a brain 18F-fluoro-ethyl-tyrosine([18F]FET) PET/MRI] complete response to the combination therapy with dabrafenib plus trametinib and silybin, a potent STAT3 inhibitor. The patient is currently undergoing treatment after a total of 24 months of continuation therapy with a good safety profile. In conclusion, we showed a promising activity of the personalized treatment of BRAF and MEK inhibitors in patient with BRAFV600E mutant glioblastoma; silybin can play an important role in decreasing drug resistance during BRAF inhibitor therapy, especially in patients with SOX2 amplification
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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